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Trial record 7 of 10 for:    Melflufen

Safety and Efficacy of Melflufen and Dexamethasone in Relapsed and/or Relapsed-Refractory Multiple Myeloma Patients

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ClinicalTrials.gov Identifier: NCT01897714
Recruitment Status : Terminated (The study was terminated at median 46-48 months long term follow-up and mature overall survival follow-up data.)
First Posted : July 12, 2013
Results First Posted : August 24, 2020
Last Update Posted : October 23, 2020
Sponsor:
Information provided by (Responsible Party):
Oncopeptides AB

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Relapsed and/or Relapsed-refractory Multiple Myeloma
Interventions Drug: Melflufen
Drug: Dexamethasone
Enrollment 75
Recruitment Details This was an open-label, Phase I/IIa study conducted at 7 study centers in 5 countries in patients with relapsed and/or relapsed-refractory Multiple Myeloma (MM). Overall, 75 patients (23 during Phase I and 52 additional patients during Phase II) were enrolled. The study results are presented until the end of trial (EOT) date of 29 October 2019.
Pre-assignment Details The study was conducted in 2 parts: Phase I (dose escalation) and Phase II (maximum tolerated dose [MTD]). During Phase I, the standard 3 + 3 design was followed with 3 to 6 patients tested at each dose level, depending on the dose limiting toxicity (DLT) observed. During Phase II, patients were treated at the MTD determined in Phase I.
Arm/Group Title Phase I: Melflufen 15 mg + Dexamethasone Phase I: Melflufen 25 mg + Dexamethasone Phase I: Melflufen 40 mg + Dexamethasone Phase I: Melflufen 55 mg + Dexamethasone Phase I + II: Melflufen 40 mg + Dexamethasone Phase II: Melflufen 40 mg (Single Agent)
Hide Arm/Group Description Patients were treated with 15 milligram (mg) melflufen as intravenous (IV) infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. Patients were treated with 25 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. Patients were treated with 55 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle. Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Period Title: Phase I (Dose Escalation)
Started 4 7 6 6 0 0
Completed [1] 1 0 1 0 0 0
Not Completed 3 7 5 6 0 0
Reason Not Completed
Disease progression             3             5             1             3             0             0
Adverse Event             0             1             4             3             0             0
Other             0             1             0             0             0             0
[1]
Completed 8 cycles or more of study drug.
Period Title: Phase II (MTD)
Started 0 0 0 0 45 [1] 13
Completed 0 0 0 0 15 2
Not Completed 0 0 0 0 30 11
Reason Not Completed
Withdrawal by Subject             0             0             0             0             0             1
Lost to Follow-up             0             0             0             0             1             0
Death             0             0             0             0             25             10
Study terminated with patient alive             0             0             0             0             1             0
Other             0             0             0             0             3             0
[1]
6 patients were entered from the Phase I: Melflufen 40 mg + Dexamethasone arm.
Arm/Group Title Phase I: Melflufen 15 mg + Dexamethasone Phase I: Melflufen 25 mg + Dexamethasone Phase I: Melflufen 40 mg + Dexamethasone Phase I: Melflufen 55 mg + Dexamethasone Phase I + II: Melflufen 40 mg + Dexamethasone Phase II: Melflufen 40 mg (Single Agent) Total
Hide Arm/Group Description Patients were treated with 15 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. Patients were treated with 25 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. Patients were treated with 55 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle. Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. Total of all reporting groups
Overall Number of Baseline Participants 4 7 6 6 45 13 81
Hide Baseline Analysis Population Description
The Safety Analysis Set included all patients who received at least 1 dose, or part thereof, of study drug.
Age, Categorical   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Phase I Number Analyzed 4 participants 7 participants 6 participants 6 participants 0 participants 0 participants 23 participants
<=18 years 0 0 0 0 0
Between 18 and 65 years 1 3 3 2 9
>=65 years 3 4 3 4 14
Phase II Number Analyzed 0 participants 0 participants 0 participants 0 participants 45 participants 13 participants 58 participants
<=18 years 0 0 0
Between 18 and 65 years 20 8 28
>=65 years 25 5 30
[1]
Measure Analysis Population Description: 6 patients from the Phase I: Melflufen 40 mg + Dexamethasone arm were transferred to Phase I + II: Melflufen 40 mg + Dexamethasone arm. All arms for the baseline analysis were not mutually exclusive (mutually exclusive patients = 75).
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Phase I Number Analyzed 4 participants 7 participants 6 participants 6 participants 0 participants 0 participants 23 participants
Female 2 4 2 3 11
Male 2 3 4 3 12
Phase II Number Analyzed 0 participants 0 participants 0 participants 0 participants 45 participants 13 participants 58 participants
Female 15 5 20
Male 30 8 38
[1]
Measure Analysis Population Description: 6 patients from the Phase I: Melflufen 40 mg + Dexamethasone arm were transferred to Phase I + II: Melflufen 40 mg + Dexamethasone arm. All arms for the baseline analysis were not mutually exclusive (mutually exclusive patients = 75).
Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Phase I Number Analyzed 4 participants 7 participants 6 participants 6 participants 0 participants 0 participants 23 participants
Black or African American 1 1 0 0 2
Caucasian 3 6 6 6 21
Not collected as per local laws 0 0 0 0 0
Phase II Number Analyzed 0 participants 0 participants 0 participants 0 participants 45 participants 13 participants 58 participants
Black or African American 3 3 6
Caucasian 41 10 51
Not collected as per local laws 1 0 1
[1]
Measure Analysis Population Description: 6 patients from the Phase I: Melflufen 40 mg + Dexamethasone arm were transferred to Phase I + II: Melflufen 40 mg + Dexamethasone arm. All arms for the baseline analysis were not mutually exclusive (mutually exclusive patients = 75).
Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Phase I Number Analyzed 4 participants 7 participants 6 participants 6 participants 0 participants 0 participants 23 participants
Hispanic or Latino 0 1 0 0 1
Not Hispanic or Latino 4 6 5 5 20
Not collected as per local laws 0 0 1 1 2
Phase II Number Analyzed 0 participants 0 participants 0 participants 0 participants 45 participants 13 participants 58 participants
Hispanic or Latino 1 0 1
Not Hispanic or Latino 37 12 49
Not collected as per local laws 7 1 8
[1]
Measure Analysis Population Description: 6 patients from the Phase I: Melflufen 40 mg + Dexamethasone arm were transferred to Phase I + II: Melflufen 40 mg + Dexamethasone arm. All arms for the baseline analysis were not mutually exclusive (mutually exclusive patients = 75).
1.Primary Outcome
Title Percentage of Patients Who Achieved Best Overall Disease Response
Hide Description The best overall disease response on treatment including stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), stable disease (SD) or progressive disease (PD) were evaluated. Starting on completion of Cycle 2, response was assessed according to International Myeloma Working Group (IMWG) criteria based on Investigator's assessment for all patients at every cycle during treatment period. PD was defined as increase of ≥25% from lowest response value in any 1 of the following: serum M-component (absolute increase must be ≥0.5 gram/deciliter) and/or urine M-component (absolute increase must be ≥200 mg/24 hr); development of new bone lesions or soft tissue plasmacytomas or increase in size of existing bone lesions or soft tissue plasmacytomas or development of hypercalcemia that could be attributed solely to plasma cell proliferative disorder. SD was defined as not meeting criteria for CR, VGPR, PR or PD.
Time Frame Baseline (Cycle 1 Day 1) and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Hide Outcome Measure Data
Hide Analysis Population Description

For Phase I arms: The Safety Analysis Set included all patients who received at least 1 dose, or part thereof, of study drug.

For Phase II arms: Modified Intent-to-Treat (mITT) Analysis Set included all patients considered to be valid for Safety Analysis Set and who received at least 1 dose of study drug at the MTD as initial dose.

Arm/Group Title Phase I: Melflufen 15 mg + Dexamethasone Phase I: Melflufen 25 mg + Dexamethasone Phase I: Melflufen 40 mg + Dexamethasone Phase I: Melflufen 55 mg + Dexamethasone Phase I + II: Melflufen 40 mg + Dexamethasone Phase II: Melflufen 40 mg (Single Agent)
Hide Arm/Group Description:
Patients were treated with 15 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Patients were treated with 25 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Patients were treated with 55 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Overall Number of Participants Analyzed 4 7 6 6 45 13
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
sCR
0.0
(0.0 to 60.2)
0.0
(0.0 to 41.0)
0.0
(0.0 to 45.9)
0.0
(0.0 to 45.9)
0.0
(0.0 to 7.9)
0.0
(0.0 to 24.7)
CR
0.0
(0.0 to 60.2)
0.0
(0.0 to 41.0)
0.0
(0.0 to 45.9)
0.0
(0.0 to 45.9)
0.0
(0.0 to 7.9)
0.0
(0.0 to 24.7)
VGPR
0.0
(0.0 to 60.2)
0.0
(0.0 to 41.0)
16.7
(0.4 to 64.1)
16.7
(0.4 to 64.1)
11.1
(3.7 to 24.1)
0.0
(0.0 to 24.7)
PR
0.0
(0.0 to 60.2)
0.0
(0.0 to 41.0)
50.0
(11.8 to 88.2)
0.0
(0.0 to 45.9)
20.0
(9.6 to 34.6)
7.7
(0.2 to 36.0)
MR
0.0
(0.0 to 60.2)
0.0
(0.0 to 41.0)
0.0
(0.0 to 45.9)
0.0
(0.0 to 45.9)
17.8
(8.0 to 32.1)
15.4
(1.9 to 45.4)
SD
75.0
(19.4 to 99.4)
42.9
(9.9 to 81.6)
16.7
(0.4 to 64.1)
66.7
(22.3 to 95.7)
26.7
(14.6 to 41.9)
69.2
(38.6 to 90.9)
PD
25.0
(0.6 to 80.6)
57.1
(18.4 to 90.1)
16.7
(0.4 to 64.1)
16.7
(0.4 to 64.1)
15.6
(6.5 to 29.5)
7.7
(0.2 to 36.0)
Missing
0.0
(0.0 to 60.2)
0.0
(0.0 to 41.0)
0.0
(0.0 to 45.9)
0.0
(0.0 to 45.9)
8.9
(2.5 to 21.2)
0.0
(0.0 to 24.7)
sCR + CR
0.0
(0.0 to 60.2)
0.0
(0.0 to 41.0)
0.0
(0.0 to 45.9)
0.0
(0.0 to 45.9)
0.0
(0.0 to 7.9)
0.0
(0.0 to 24.7)
sCR + CR + VGPR
0.0
(0.0 to 60.2)
0.0
(0.0 to 41.0)
16.7
(0.4 to 64.1)
16.7
(0.4 to 64.1)
11.1
(3.7 to 24.1)
0.0
(0.0 to 24.7)
2.Primary Outcome
Title Overall Response Rate (ORR)
Hide Description ORR was defined as percentage of patients with an overall response (OR), defined as first occurrence of confirmed disease response including PR or better (i.e, PR, VGPR, CR or sCR). Starting on completion of Cycle 2, response was assessed according to IMWG criteria based on Investigator's assessment for all patients at every cycle during treatment period. VGPR was defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum plus urine M-protein level <100 mg/24hr and >90% decrease in difference between involved and uninvolved free light chain (FLC) levels (only in FLC diseased patients). CR was defined as negative immunofixation on serum and urine, loss of any soft tissue plasmacytomas, <5% plasma cells in bone marrow and normal FLC ratio of 0.26 to 1.65 (only in FLC diseased patients). sCR was defined as CR plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or 2 to 4 color flow cytometry.
Time Frame Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Hide Outcome Measure Data
Hide Analysis Population Description

For Phase I arms: The Safety Analysis Set included all patients who received at least 1 dose, or part thereof, of study drug.

For Phase II arms: The mITT Analysis Set included all patients considered to be valid for the Safety Analysis Set and who received at least 1 dose of study drug at the MTD as the initial dose.

Arm/Group Title Phase I: Melflufen 15 mg + Dexamethasone Phase I: Melflufen 25 mg + Dexamethasone Phase I: Melflufen 40 mg + Dexamethasone Phase I: Melflufen 55 mg + Dexamethasone Phase I + II: Melflufen 40 mg + Dexamethasone Phase II: Melflufen 40 mg (Single Agent)
Hide Arm/Group Description:
Patients were treated with 15 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Patients were treated with 25 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Patients were treated with 55 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Overall Number of Participants Analyzed 4 7 6 6 45 13
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
0.0
(0.0 to 60.2)
0.0
(0.0 to 41.0)
66.7
(22.3 to 95.7)
16.7
(0.4 to 64.1)
31.1
(18.2 to 46.6)
7.7
(0.2 to 36.0)
3.Primary Outcome
Title Clinical Benefit Response Rate (CBRR)
Hide Description The CBRR was defined as the percentage of patients with a clinical benefit response (CBR), defined as the first occurrence of confirmed disease response including MR or better (i.e, MR, PR, VGPR, CR, or sCR). Starting on completion of Cycle 2, response was assessed according to the IMWG criteria based on the Investigator's assessment for all patients at every cycle during the treatment period. MR was defined as ≥25% but <49% reduction of serum M-protein and reduction in 24 hour urine M-protein by 50 to 89%, which still exceeds 200 mg/24 hours. In addition to above; if present at baseline, 25 to 49% reduction in the size of soft tissue plasmacytomas is also required. No increase in size or number of lytic bone lesions (development of compression fractures does not exclude response). PR was defined as 50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by ≥90% or to <200 mg/24 hour.
Time Frame Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Hide Outcome Measure Data
Hide Analysis Population Description

For Phase I arms: The Safety Analysis Set included all patients who received at least 1 dose, or part thereof, of study drug.

For Phase II arms: The mITT Analysis Set included all patients considered to be valid for the Safety Analysis Set and who received at least 1 dose of study drug at the MTD as the initial dose.

Arm/Group Title Phase I: Melflufen 15 mg + Dexamethasone Phase I: Melflufen 25 mg + Dexamethasone Phase I: Melflufen 40 mg + Dexamethasone Phase I: Melflufen 55 mg + Dexamethasone Phase I + II: Melflufen 40 mg + Dexamethasone Phase II: Melflufen 40 mg (Single Agent)
Hide Arm/Group Description:
Patients were treated with 15 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Patients were treated with 25 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Patients were treated with 55 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Overall Number of Participants Analyzed 4 7 6 6 45 13
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
0.0
(0.0 to 60.2)
0.0
(0.0 to 41.0)
66.7
(22.3 to 95.7)
16.7
(0.4 to 64.1)
48.9
(33.7 to 64.2)
23.1
(5.0 to 53.8)
4.Secondary Outcome
Title Duration of Disease Response (DOR)
Hide Description The DOR to treatment was defined as time from first response (PR or better) to disease progression or death, or date of last evaluable disease response assessment for those who had not progressed or died. DOR was estimated using Kaplan-Meier statistics.
Time Frame Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT Analysis Set included all patients considered to be valid for the Safety Analysis Set and who received at least 1 dose of study drug at the MTD as the initial dose. Only patients who had achieved at least PR were evaluated.
Arm/Group Title Phase I + II: Melflufen 40 mg + Dexamethasone Phase II: Melflufen 40 mg (Single Agent)
Hide Arm/Group Description:
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Overall Number of Participants Analyzed 14 1
Median (95% Confidence Interval)
Unit of Measure: months
8.4
(4.6 to 11.1)
7.2 [1] 
(NA to NA)
[1]
The confidence interval could not be determined as only 1 patient was analysed.
5.Secondary Outcome
Title Time to Disease Response in Patients Who Achieved OR and CBR
Hide Description Time to first OR was defined as the time from the date of the first dose of study drug (overall reference start date) to the date of the first occurrence of PR or better (first of 2 consecutive assessments-confirmed response). Time to first CBR was defined as the time from the date of the first dose of study drug (overall reference start date) to the date of the first occurrence of MR or better (first of 2 consecutive assessments-confirmed response). Time to disease response was estimated using Kaplan-Meier statistics.
Time Frame Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
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Hide Analysis Population Description
The mITT Analysis Set included all patients considered to be valid for the Safety Analysis Set and who received at least 1 dose of study drug at the MTD as the initial dose. Only patients who had achieved OR and CBR were evaluated, for each respective time to response parameter.
Arm/Group Title Phase I + II: Melflufen 40 mg + Dexamethasone Phase II: Melflufen 40 mg (Single Agent)
Hide Arm/Group Description:
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Overall Number of Participants Analyzed 22 3
Median (95% Confidence Interval)
Unit of Measure: months
OR Number Analyzed 14 participants 1 participants
2.8
(1.6 to 4.7)
6.7 [1] 
(NA to NA)
CBR Number Analyzed 22 participants 3 participants
2.4
(1.4 to 3.0)
2.8
(2.8 to 6.1)
[1]
The confidence interval could not be determined as only 1 patient was analysed.
6.Secondary Outcome
Title Time to Disease Progression
Hide Description Time to disease progression was defined as the time from the date of the first dose of study drug (overall reference start date) to the date of the first occurrence of evaluable PD. Time to disease progression was estimated using Kaplan-Meier statistics.
Time Frame Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
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Hide Analysis Population Description
The mITT Analysis Set included all patients considered to be valid for the Safety Analysis Set and who received at least 1 dose of study drug at the MTD as the initial dose.
Arm/Group Title Phase I + II: Melflufen 40 mg + Dexamethasone Phase II: Melflufen 40 mg (Single Agent)
Hide Arm/Group Description:
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Overall Number of Participants Analyzed 45 13
Median (95% Confidence Interval)
Unit of Measure: months
6.5
(3.7 to 9.3)
4.4
(2.8 to 12.2)
7.Secondary Outcome
Title Median Progression-Free Survival (PFS)
Hide Description The PFS was defined as the time from the date of the first dose of melflufen (overall reference start date) to the date of the first occurrence of any disease response assessment available for PD or death. The PFS was estimated using Kaplan-Meier statistics.
Time Frame Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
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Hide Analysis Population Description
The mITT Analysis Set included all patients considered to be valid for the Safety Analysis Set and who received at least 1 dose of study drug at the MTD as the initial dose. Only patients who had information about PFS at the time of EOT (29 October 2019) were reported.
Arm/Group Title Phase I + II: Melflufen 40 mg + Dexamethasone Phase II: Melflufen 40 mg (Single Agent)
Hide Arm/Group Description:
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Overall Number of Participants Analyzed 45 13
Median (95% Confidence Interval)
Unit of Measure: months
5.7
(3.7 to 9.2)
4.4
(2.8 to 7.6)
8.Secondary Outcome
Title Median Overall Survival (OS)
Hide Description The OS was defined as the time from the date of the first dose of melflufen (overall reference start date) to death. The OS was estimated using Kaplan-Meier statistics.
Time Frame From baseline until death. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
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Hide Analysis Population Description
The mITT Analysis Set included all patients considered to be valid for the Safety Analysis Set and who received at least 1 dose of study drug at the MTD as the initial dose. Only patients who had information about OS at the time of EOT(29 October 2019) were reported.
Arm/Group Title Phase I + II: Melflufen 40 mg + Dexamethasone Phase II: Melflufen 40 mg (Single Agent)
Hide Arm/Group Description:
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Overall Number of Participants Analyzed 45 13
Median (95% Confidence Interval)
Unit of Measure: months
20.7
(11.8 to 41.3)
15.5
(4.9 to 23.4)
9.Secondary Outcome
Title Time to First Subsequent Treatment
Hide Description Time to first subsequent treatment start was defined as the time from the date of the actual end of treatment to the date of the first subsequent treatment. Time to first subsequent treatment was estimated using Kaplan-Meier statistics.
Time Frame From baseline until start of first subsequent treatment. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT Analysis Set included all patients considered to be valid for the Safety Analysis Set and who received at least 1 dose of study drug at the MTD as the initial dose. Only patients who had information about first subsequent treatment at the time of EOT (29 October 2019) were reported.
Arm/Group Title Phase I + II: Melflufen 40 mg + Dexamethasone Phase II: Melflufen 40 mg (Single Agent)
Hide Arm/Group Description:
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Overall Number of Participants Analyzed 45 13
Median (95% Confidence Interval)
Unit of Measure: months
10.5
(7.9 to 12.2)
10.7 [1] 
(5.3 to NA)
[1]
Upper limit of confidence could not be calculated as it was not reached.
10.Secondary Outcome
Title Number of Patients With Treatment Emergent Adverse Events (TEAEs)
Hide Description An adverse event (AE) was any untoward medical occurrence in a study patient administered an investigational product and that does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was defined as any AE, occurring at any dose, that met any one or more of the following criteria: is fatal or immediately life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; is medically significant; requires inpatient hospitalization or prolongation of existing hospitalization; or other important medical event. TEAEs were defined as AEs that started or worsened on or after the first dose of study drug (overall reference start date) up to and including the actual EOT date. TESAEs = Treatment emergent serious adverse events.
Time Frame From the first dose of study drug up to and including the actual EOT date of 29 October 2019; up to a maximum of approximately 76 months.
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Hide Analysis Population Description
The Safety Analysis Set included all patients who received at least 1 dose, or part thereof, of study drug.
Arm/Group Title Phase I: Melflufen 15 mg + Dexamethasone Phase I: Melflufen 25 mg + Dexamethasone Phase I: Melflufen 40 mg + Dexamethasone Phase I: Melflufen 55 mg + Dexamethasone Phase I + II: Melflufen 40 mg + Dexamethasone Phase II: Melflufen 40 mg (Single Agent)
Hide Arm/Group Description:
Patients were treated with 15 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Patients were treated with 25 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Patients were treated with 55 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Overall Number of Participants Analyzed 4 7 6 6 45 13
Measure Type: Count of Participants
Unit of Measure: Participants
TEAEs (including both serious and non-serious AEs) Number Analyzed 4 participants 7 participants 6 participants 6 participants 45 participants 13 participants
4 7 6 6 45 13
TEAEs leading to death Number Analyzed 4 participants 7 participants 6 participants 6 participants 45 participants 13 participants
0 1 0 0 3 0
TESAEs Number Analyzed 4 participants 7 participants 6 participants 6 participants 45 participants 13 participants
3 4 2 4 17 9
DLT TEAEs Number Analyzed 4 participants 7 participants 6 participants 6 participants 0 participants 0 participants
0 0 0 4
TEAEs related to melflufen and/or dexamethasone Number Analyzed 4 participants 7 participants 6 participants 6 participants 45 participants 13 participants
4 7 6 6 45 13
TESAEs related to melflufen and/or dexamethasone Number Analyzed 4 participants 7 participants 6 participants 6 participants 45 participants 13 participants
3 4 2 4 17 9
Time Frame From the first dose of study drug up to and including the actual EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Adverse Event Reporting Description The Safety Analysis Set included all patients who received at least 1 dose, or part thereof, of study drug.
 
Arm/Group Title Phase I: Melflufen 15 mg + Dexamethasone Phase I: Melflufen 25 mg + Dexamethasone Phase I: Melflufen 40 mg + Dexamethasone Phase I: Melflufen 55 mg + Dexamethasone Phase I + II: Melflufen 40 mg + Dexamethasone Phase II: Melflufen 40 mg (Single Agent)
Hide Arm/Group Description Patients were treated with 15 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. Patients were treated with 25 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. Patients were treated with 55 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle. Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
All-Cause Mortality
Phase I: Melflufen 15 mg + Dexamethasone Phase I: Melflufen 25 mg + Dexamethasone Phase I: Melflufen 40 mg + Dexamethasone Phase I: Melflufen 55 mg + Dexamethasone Phase I + II: Melflufen 40 mg + Dexamethasone Phase II: Melflufen 40 mg (Single Agent)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/4 (75.00%)      5/7 (71.43%)      2/6 (33.33%)      5/6 (83.33%)      30/45 (66.67%)      10/13 (76.92%)    
Hide Serious Adverse Events
Phase I: Melflufen 15 mg + Dexamethasone Phase I: Melflufen 25 mg + Dexamethasone Phase I: Melflufen 40 mg + Dexamethasone Phase I: Melflufen 55 mg + Dexamethasone Phase I + II: Melflufen 40 mg + Dexamethasone Phase II: Melflufen 40 mg (Single Agent)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/4 (75.00%)      4/7 (57.14%)      2/6 (33.33%)      4/6 (66.67%)      17/45 (37.78%)      9/13 (69.23%)    
Blood and lymphatic system disorders             
Neutropenia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 3/6 (50.00%)  3 2/45 (4.44%)  2 1/13 (7.69%)  1
Febrile neutropenia  1  1/4 (25.00%)  1 0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 2/45 (4.44%)  2 0/13 (0.00%)  0
Thrombocytopenia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 2/13 (15.38%)  10
Cardiac disorders             
Atrial fibrillation  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 1/13 (7.69%)  1
Gastrointestinal disorders             
Nausea  1  1/4 (25.00%)  1 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Vomiting  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/45 (0.00%)  0 0/13 (0.00%)  0
Diarrhoea  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  3 0/13 (0.00%)  0
General disorders             
Pyrexia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 2/45 (4.44%)  2 1/13 (7.69%)  1
Infections and infestations             
Pneumonia  1  1/4 (25.00%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 2/6 (33.33%)  2 5/45 (11.11%)  5 1/13 (7.69%)  1
Bacteraemia  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Cystitis  1  1/4 (25.00%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Escherichia bacteraemia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/45 (0.00%)  0 0/13 (0.00%)  0
Sepsis  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/45 (0.00%)  0 0/13 (0.00%)  0
Upper respiratory tract infection  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Urinary tract infection  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/45 (0.00%)  0 0/13 (0.00%)  0
Escherichia sepsis  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  2 0/13 (0.00%)  0
Catheter site infection  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 1/13 (7.69%)  1
Parainfluenzae virus infection  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Pseudomonal sepsis  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 1/13 (7.69%)  1
Injury, poisoning and procedural complications             
Spinal compression fracture  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Spinal fracture  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Investigations             
White blood cell count decreased  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 1/13 (7.69%)  1
Metabolism and nutrition disorders             
Hyperphosphataemia  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Diabetes mellitus  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Hypercalcaemia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  2 0/13 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Arthralgia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/45 (0.00%)  0 0/13 (0.00%)  0
Bone lesion  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Spinal disorder  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Plasmacytoma  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 1/13 (7.69%)  1
Nervous system disorders             
Spinal cord compression  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 1/13 (7.69%)  1
Renal and urinary disorders             
Renal failure  1  1/4 (25.00%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Acute kidney injury  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Pneumonitis  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Vascular disorders             
Deep vein thrombosis  1  1/4 (25.00%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Phase I: Melflufen 15 mg + Dexamethasone Phase I: Melflufen 25 mg + Dexamethasone Phase I: Melflufen 40 mg + Dexamethasone Phase I: Melflufen 55 mg + Dexamethasone Phase I + II: Melflufen 40 mg + Dexamethasone Phase II: Melflufen 40 mg (Single Agent)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/4 (100.00%)      7/7 (100.00%)      6/6 (100.00%)      6/6 (100.00%)      45/45 (100.00%)      12/13 (92.31%)    
Blood and lymphatic system disorders             
Thrombocytopenia  1  2/4 (50.00%)  2 6/7 (85.71%)  9 4/6 (66.67%)  26 5/6 (83.33%)  35 33/45 (73.33%)  154 9/13 (69.23%)  30
Neutropenia  1  1/4 (25.00%)  1 3/7 (42.86%)  7 3/6 (50.00%)  12 6/6 (100.00%)  26 31/45 (68.89%)  115 9/13 (69.23%)  25
Anaemia  1  3/4 (75.00%)  3 4/7 (57.14%)  5 2/6 (33.33%)  4 3/6 (50.00%)  6 29/45 (64.44%)  96 5/13 (38.46%)  14
Lymphopenia  1  1/4 (25.00%)  2 1/7 (14.29%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 3/45 (6.67%)  3 1/13 (7.69%)  3
Leukopenia  1  1/4 (25.00%)  2 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Pancytopenia  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 1/45 (2.22%)  1 0/13 (0.00%)  0
Anaemia vitamin B12 deficiency  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Increased tendency to bruise  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/45 (0.00%)  0 0/13 (0.00%)  0
Bone marrow failure  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Cardiac disorders             
Palpitations  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0 2/45 (4.44%)  3 0/13 (0.00%)  0
Mitral valve disease mixed  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Sinus tachycardia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Ear and labyrinth disorders             
Ear haemorrhage  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Eye disorders             
Vision blurred  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/45 (0.00%)  0 0/13 (0.00%)  0
Gastrointestinal disorders             
Nausea  1  1/4 (25.00%)  1 0/7 (0.00%)  0 4/6 (66.67%)  6 4/6 (66.67%)  5 12/45 (26.67%)  14 2/13 (15.38%)  3
Constipation  1  2/4 (50.00%)  2 3/7 (42.86%)  3 1/6 (16.67%)  1 0/6 (0.00%)  0 7/45 (15.56%)  8 1/13 (7.69%)  1
Diarrhoea  1  0/4 (0.00%)  0 0/7 (0.00%)  0 2/6 (33.33%)  3 4/6 (66.67%)  5 9/45 (20.00%)  10 2/13 (15.38%)  2
Vomiting  1  0/4 (0.00%)  0 0/7 (0.00%)  0 2/6 (33.33%)  2 2/6 (33.33%)  2 5/45 (11.11%)  5 1/13 (7.69%)  1
Abdominal pain upper  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 3/45 (6.67%)  5 0/13 (0.00%)  0
Abdominal pain  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 2/45 (4.44%)  4 0/13 (0.00%)  0
Dyspepsia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 3/45 (6.67%)  3 0/13 (0.00%)  0
Gastrointestinal disorder  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Oral pain  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Stomatitis  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 3/45 (6.67%)  3 0/13 (0.00%)  0
Abdominal distension  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  6 0/13 (0.00%)  0
Abdominal hernia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Aerophagia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Gastric disorder  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  3 0/13 (0.00%)  0
General disorders             
Fatigue  1  1/4 (25.00%)  1 3/7 (42.86%)  5 3/6 (50.00%)  7 2/6 (33.33%)  2 13/45 (28.89%)  20 4/13 (30.77%)  4
Pyrexia  1  2/4 (50.00%)  2 0/7 (0.00%)  0 2/6 (33.33%)  2 1/6 (16.67%)  1 16/45 (35.56%)  19 0/13 (0.00%)  0
Mucosal inflammation  1  0/4 (0.00%)  0 1/7 (14.29%)  1 1/6 (16.67%)  1 1/6 (16.67%)  2 6/45 (13.33%)  8 0/13 (0.00%)  0
Hyperthermia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 1/45 (2.22%)  1 0/13 (0.00%)  0
Asthenia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  3 14/45 (31.11%)  46 0/13 (0.00%)  0
Chest pain  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Influenza like illness  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 4/45 (8.89%)  4 0/13 (0.00%)  0
Non-cardiac chest pain  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Oedema peripheral  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  2 1/13 (7.69%)  1
Pain  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Application site erosion  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Chills  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 1/13 (7.69%)  1
Feeling cold  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Mucous membrane disorder  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Hepatobiliary disorders             
Cholecystitis  1  1/4 (25.00%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Immune system disorders             
Immune system disorder  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Infections and infestations             
Bronchitis  1  0/4 (0.00%)  0 0/7 (0.00%)  0 2/6 (33.33%)  2 0/6 (0.00%)  0 2/45 (4.44%)  2 0/13 (0.00%)  0
Upper respiratory tract infection  1  0/4 (0.00%)  0 1/7 (14.29%)  1 1/6 (16.67%)  2 0/6 (0.00%)  0 5/45 (11.11%)  6 0/13 (0.00%)  0
Candida infection  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/45 (0.00%)  0 0/13 (0.00%)  0
Cystitis  1  1/4 (25.00%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Enterococcal infection  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Gingivitis  1  1/4 (25.00%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Influenza  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Mucosal infection  1  1/4 (25.00%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Nasopharyngitis  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 3/45 (6.67%)  4 0/13 (0.00%)  0
Oral candidiasis  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Oral fungal infection  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  2 0/13 (0.00%)  0
Periodontitis  1  1/4 (25.00%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Pneumonia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 3/45 (6.67%)  3 1/13 (7.69%)  1
Infection  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 4/45 (8.89%)  5 0/13 (0.00%)  0
Oral herpes  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  2 1/13 (7.69%)  1
Herpes zoster  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  2 0/13 (0.00%)  0
Acarodermatitis  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Administration site infection  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 1/13 (7.69%)  1
Conjunctivitis bacterial  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Eye infection  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Furuncle  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Gastroenteritis  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Gastroenteritis viral  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 1/13 (7.69%)  1
Herpes virus infection  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Laryngitis  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Lower respiratory tract infection  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Lung infection  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Sinusitis  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Skin infection  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  2 0/13 (0.00%)  0
Vulvovaginal mycotic infection  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 1/13 (7.69%)  1
Injury, poisoning and procedural complications             
Contusion  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 3/45 (6.67%)  3 0/13 (0.00%)  0
Spinal compression fracture  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 1/13 (7.69%)  1
Humerus fracture  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Infusion related reaction  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 1/13 (7.69%)  1
Joint dislocation  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Thermal burn  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Investigations             
Blood creatinine increased  1  0/4 (0.00%)  0 3/7 (42.86%)  3 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
White blood cell count decreased  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 4/45 (8.89%)  4 3/13 (23.08%)  3
Aspartate aminotransferase increased  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Blood bilirubin increased  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 2/45 (4.44%)  2 0/13 (0.00%)  0
Blood glucose increased  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Cardiac murmur  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Protein total increased  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
C-reactive protein increased  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 4/45 (8.89%)  5 0/13 (0.00%)  0
CD4 lymphocytes decreased  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 3/45 (6.67%)  3 0/13 (0.00%)  0
Weight decreased  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  2 0/13 (0.00%)  0
Blood lactate dehydrogenase increased  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Fibrin d dimer increased  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
International normalised ratio increased  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  4 0/13 (0.00%)  0
Lymphocyte count decreased  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 1/13 (7.69%)  1
Red blood cell count decreased  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Urine output decreased  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Vitamin B12 decreased  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Weight increased  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Metabolism and nutrition disorders             
Decreased appetite  1  0/4 (0.00%)  0 1/7 (14.29%)  1 2/6 (33.33%)  4 1/6 (16.67%)  1 3/45 (6.67%)  5 1/13 (7.69%)  1
Hypoalbuminaemia  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Hypokalaemia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  2 2/45 (4.44%)  3 0/13 (0.00%)  0
Hypomagnesaemia  1  1/4 (25.00%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Hyperglycaemia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 4/45 (8.89%)  13 0/13 (0.00%)  0
Hypocalcaemia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 3/45 (6.67%)  4 0/13 (0.00%)  0
Hyponatraemia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 3/45 (6.67%)  3 0/13 (0.00%)  0
Dehydration  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  2 0/13 (0.00%)  0
Hyperuricaemia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 1/13 (7.69%)  1
Cachexia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Hypercalcaemia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  2 0/13 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Back pain  1  0/4 (0.00%)  0 3/7 (42.86%)  3 0/6 (0.00%)  0 1/6 (16.67%)  1 6/45 (13.33%)  9 2/13 (15.38%)  2
Arthralgia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 5/45 (11.11%)  5 0/13 (0.00%)  0
Bone pain  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 6/45 (13.33%)  8 0/13 (0.00%)  0
Muscle spasms  1  0/4 (0.00%)  0 1/7 (14.29%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 5/45 (11.11%)  5 0/13 (0.00%)  0
Bursitis  1  1/4 (25.00%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Musculoskeletal chest pain  1  0/4 (0.00%)  0 1/7 (14.29%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Myalgia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 2/45 (4.44%)  2 0/13 (0.00%)  0
Osteoporosis  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Spinal pain  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  4 0/13 (0.00%)  0
Musculoskeletal pain  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  4 0/13 (0.00%)  0
Flank pain  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Muscular weakness  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Myopathy  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Neck pain  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Synovial cyst  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 1/13 (7.69%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Plasmacytoma  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Nervous system disorders             
Dizziness  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 4/45 (8.89%)  4 0/13 (0.00%)  0
Headache  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  2 6/45 (13.33%)  8 0/13 (0.00%)  0
Paraesthesia  1  1/4 (25.00%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Peripheral sensory neuropathy  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Presyncope  1  1/4 (25.00%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Neuropathy peripheral  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 4/45 (8.89%)  4 0/13 (0.00%)  0
Ataxia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Somnolence  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Tremor  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Product Issues             
Device occlusion  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 1/13 (7.69%)  1
Psychiatric disorders             
Insomnia  1  1/4 (25.00%)  1 0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 6/45 (13.33%)  8 0/13 (0.00%)  0
Sleep disorder  1  0/4 (0.00%)  0 1/7 (14.29%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 2/45 (4.44%)  2 0/13 (0.00%)  0
Anxiety  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Confusional state  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Nervousness  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Mood altered  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 1/13 (7.69%)  1
Depression  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Restlessness  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Renal and urinary disorders             
Dysuria  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/45 (2.22%)  1 1/13 (7.69%)  1
Renal failure  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 1/13 (7.69%)  1
Haematuria  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Reproductive system and breast disorders             
Erectile Dysfunction  1  1/4 (25.00%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Dyspnoea  1  1/4 (25.00%)  1 0/7 (0.00%)  0 2/6 (33.33%)  2 2/6 (33.33%)  2 6/45 (13.33%)  6 1/13 (7.69%)  1
Cough  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 8/45 (17.78%)  11 0/13 (0.00%)  0
Dyspnoea exertional  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Epistaxis  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 6/45 (13.33%)  8 1/13 (7.69%)  1
Dysphonia  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  2 0/13 (0.00%)  0
Oropharyngeal pain  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  2 0/13 (0.00%)  0
Productive cough  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 1/13 (7.69%)  1
Pleural effusion  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 1/13 (7.69%)  1
Skin and subcutaneous tissue disorders             
Petechiae  1  0/4 (0.00%)  0 1/7 (14.29%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Rash  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 3/45 (6.67%)  3 0/13 (0.00%)  0
Blood blister  1  0/4 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Erythema  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Hyperhidrosis  1  0/4 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/45 (2.22%)  1 1/13 (7.69%)  1
Night sweats  1  1/4 (25.00%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Skin lesion  1  0/4 (0.00%)  0 1/7 (14.29%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0 0/45 (0.00%)  0 0/13 (0.00%)  0
Ecchymosis  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Vascular disorders             
Hypertension  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 3/45 (6.67%)  3 0/13 (0.00%)  0
Hypotension  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/45 (4.44%)  2 1/13 (7.69%)  1
Flushing  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Haematoma  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Thrombophlebitis  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
Venous thrombosis  1  0/4 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/45 (2.22%)  1 0/13 (0.00%)  0
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Study is terminated and long-term follow-up ended due to Sponsor decision.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Eva Nordström
Organization: Oncopeptides AB
Phone: +4686152040
EMail: trials@oncopeptides.com
Layout table for additonal information
Responsible Party: Oncopeptides AB
ClinicalTrials.gov Identifier: NCT01897714    
Other Study ID Numbers: O-12-M1
First Submitted: July 9, 2013
First Posted: July 12, 2013
Results First Submitted: June 29, 2020
Results First Posted: August 24, 2020
Last Update Posted: October 23, 2020