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Lenalidomide and High-Dose Melphalan

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ClinicalTrials.gov Identifier: NCT01079936
Recruitment Status : Completed
First Posted : March 3, 2010
Results First Posted : June 6, 2016
Last Update Posted : June 6, 2016
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Myeloma
Stem Cell Transplantation
Interventions Drug: Lenalidomide
Drug: Melphalan
Procedure: Stem Cell Infusion
Enrollment 61
Recruitment Details Recruitment Period: March 01, 2010 to April 18, 2013. All recruitment done at The University of Texas MD Anderson Cancer Center.
Pre-assignment Details Following Phase I portion of study, participants were assigned using adaptive randomization to 1 of 4 dose levels in Phase II. Out of 61 participants consented, 2 participants were ineligible for study due to first remission status and 2 participants did not receive stem cell transplant due to other issues and are not included in study demographic.
Arm/Group Title Phase I: Lenalidomide + High-Dose Melphalan 25 Mg Lenalidomide 50 mg Lenalidomide 75 mg Lenalidomide 100 mg Lenalidomide
Hide Arm/Group Description Lenalidomide beginning dose level 25 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0. Lenalidomide dose level 25 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0. Lenalidomide dose level 50 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0. Lenalidomide dose level 75 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0. Lenalidomide dose level 100 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0.
Period Title: Phase I: MTD
Started 16 0 0 0 0
Completed 12 [1] 0 0 0 0
Not Completed 4 0 0 0 0
Reason Not Completed
First Remission Status             2             0             0             0             0
No Stem Cell Transplantation             2             0             0             0             0
[1]
The 12 Phase I participants were randomized across 4 dose arms for Phase II.
Period Title: Phase II
Started 0 3 6 24 26
Completed 0 3 5 24 25
Not Completed 0 0 1 0 1
Reason Not Completed
Adverse Event             0             0             1             0             0
Insurance Issue             0             0             0             0             1
Arm/Group Title 25 Mg Lenalidomide 50 mg Lenalidomide 75 mg Lenalidomide 100 mg Lenalidomide Total
Hide Arm/Group Description Lenalidomide dose level 25 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0. Lenalidomide dose level 50 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0. Lenalidomide dose level 75 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0. Lenalidomide dose level 100 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0. Total of all reporting groups
Overall Number of Baseline Participants 3 6 24 26 59
Hide Baseline Analysis Population Description
Two participants were not eligible for study, and another two were eligible but did not receive required stem cell transplant therefore all appear in participation flow but two ineligible are not in baseline analysis population demographics.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 3 participants 6 participants 24 participants 26 participants 59 participants
59
(50 to 63)
66
(53 to 70)
55
(34 to 72)
60
(52 to 71)
59.5
(34 to 72)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 6 participants 24 participants 26 participants 59 participants
Female
2
  66.7%
4
  66.7%
12
  50.0%
13
  50.0%
31
  52.5%
Male
1
  33.3%
2
  33.3%
12
  50.0%
13
  50.0%
28
  47.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 3 participants 6 participants 24 participants 26 participants 59 participants
3 6 24 26 59
1.Primary Outcome
Title Maximum Tolerated Dose (MTD) of Lenalidomide
Hide Description There were 4 doses of lenalidomide in the dose escalation phase: 25 mg, 50 mg, 75 mg, and 100 mg. The first 12 patients were treated at these dose levels (3 patients per level) and safety assessed at each level. The MTD dose level was to be the level at which participants at each lenalidomide dose level had no dose limiting toxicity (DLT). DLT defined as as regimen-related death, graft failure, grade 3 or 4 atrial fibrillation, grade 4 deep venous thrombosis, or pulmonary embolism before day 30 after auto-HCT. Each participant received a fixed dose of Melphalan plus one of the four doses 25, 50, 75 or 100 mg of Lenalidomide orally for each of 7 days, -8 to -2 pre transplant.
Time Frame Assessed at 21-28 Day Cycle
Hide Outcome Measure Data
Hide Analysis Population Description
Of the 16 participants in Phase I, two participants were not eligible for study due to first remission status, and two were eligible but did not receive stem cell transplant due to other issues.
Arm/Group Title Lenalidomide + High-Dose Melphalan
Hide Arm/Group Description:

Lenalidomide beginning dose level 25 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0.

Lenalidomide: Beginning dose level 25 mg by mouth (PO) on Days -8 to -2

Melphalan: Dose level 100 mg/m2 by vein (IV) Days -3 and -2 over 30 minutes infusion

Stem Cell Infusion: Stem cell infusion on Day 0.

Overall Number of Participants Analyzed 12
Measure Type: Number
Unit of Measure: mg/day
100
2.Primary Outcome
Title Number of Participants With Response (CR at Day 90)
Hide Description Response is defined as the event that the participant is alive with complete response (CR) at day 90 (+/-30 days). CR defined as: A) Absence of monoclonal protein in urine and serum when analyzed by immunofixation electrophoresis. B) The bone marrow should be normal by morphological examination with <5% plasma cells. There should be < 1% aneuploid light chain restricted population by flow cytometry for DNA/cIg. C) While healing of bone lesions not required, no new lytic lesion should appear. Further compression fracture of spine will be not considered as progressive disease.
Time Frame Day 90 after stem cell transplant
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 25 Mg Lenalidomide 50 mg Lenalidomide 75 mg Lenalidomide 100 mg Lenalidomide
Hide Arm/Group Description:
Lenalidomide dose level 25 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0.
Lenalidomide dose level 50 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0.
Lenalidomide dose level 75 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0.
Lenalidomide dose level 100 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0.
Overall Number of Participants Analyzed 3 5 24 25
Measure Type: Number
Unit of Measure: participants
0 0 4 4
3.Primary Outcome
Title Number of Participants With Day 30 DLT (Overall Study, Phase I/Phase II)
Hide Description Dose limiting toxicity (DLT) was defined as regimen-related death, graft failure, grade 3 or 4 atrial fibrillation, grade 4 deep venous thrombosis, or pulmonary embolism before day 30 after auto-HCT.
Time Frame Day 30 following transplant
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 25 Mg Lenalidomide 50 mg Lenalidomide 75 mg Lenalidomide 100 mg Lenalidomide
Hide Arm/Group Description:
Lenalidomide dose level 25 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0.
Lenalidomide dose level 50 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0.
Lenalidomide dose level 75 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0.
Lenalidomide dose level 100 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0.
Overall Number of Participants Analyzed 3 5 24 25
Measure Type: Number
Unit of Measure: participants
0 0 2 0
4.Primary Outcome
Title Participants With Grade 3 =/> Adverse Events
Hide Description Number of participants experiencing adverse events above a Grade 3 according to the Common Terminology Criteria for Adverse Events (CTCAE) version 2.
Time Frame Day 90 after stem cell transplant
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 25 Mg Lenalidomide 50 mg Lenalidomide 75 mg Lenalidomide 100 mg Lenalidomide
Hide Arm/Group Description:
Lenalidomide dose level 25 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0.
Lenalidomide dose level 50 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0.
Lenalidomide dose level 75 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0.
Lenalidomide dose level 100 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0.
Overall Number of Participants Analyzed 3 5 24 25
Measure Type: Number
Unit of Measure: participants
3 5 15 17
Time Frame Adverse event collection from the start of preparative regiment up to Day 30 following stem cell transplant.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 25 Mg Lenalidomide 50 mg Lenalidomide 75 mg Lenalidomide 100 mg Lenalidomide
Hide Arm/Group Description Lenalidomide dose level 25 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0. Lenalidomide dose level 50 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0. Lenalidomide dose level 75 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0. Lenalidomide dose level 100 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m^2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0.
All-Cause Mortality
25 Mg Lenalidomide 50 mg Lenalidomide 75 mg Lenalidomide 100 mg Lenalidomide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
25 Mg Lenalidomide 50 mg Lenalidomide 75 mg Lenalidomide 100 mg Lenalidomide
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/3 (0.00%)      0/6 (0.00%)      1/24 (4.17%)      1/26 (3.85%)    
Blood and lymphatic system disorders         
Blood Platelets  1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/24 (0.00%)  0 1/26 (3.85%)  1
Infections and infestations         
Infection  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/24 (4.17%)  1 0/26 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (2.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
25 Mg Lenalidomide 50 mg Lenalidomide 75 mg Lenalidomide 100 mg Lenalidomide
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/3 (100.00%)      6/6 (100.00%)      22/24 (91.67%)      25/26 (96.15%)    
Blood and lymphatic system disorders         
Change in Platelet levels  1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/24 (0.00%)  0 1/26 (3.85%)  1
Cardiac disorders         
High blood pressure  1  0/3 (0.00%)  0 0/6 (0.00%)  0 2/24 (8.33%)  2 2/26 (7.69%)  2
Tachycardia  1  0/3 (0.00%)  0 0/6 (0.00%)  0 2/24 (8.33%)  2 3/26 (11.54%)  3
Gastrointestinal disorders         
Herpetic lip leson  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/24 (4.17%)  1 0/26 (0.00%)  0
Diarrhea  1  1/3 (33.33%)  1 6/6 (100.00%)  6 22/24 (91.67%)  22 21/26 (80.77%)  21
GI DPH  1  2/3 (66.67%)  2 4/6 (66.67%)  4 10/24 (41.67%)  10 13/26 (50.00%)  13
Nausea  1  3/3 (100.00%)  3 6/6 (100.00%)  6 22/24 (91.67%)  22 25/26 (96.15%)  25
General disorders         
Flu like symptoms  1  0/3 (0.00%)  0 0/6 (0.00%)  0 9/24 (37.50%)  9 13/26 (50.00%)  13
Fever, Flu-like  1  1/3 (33.33%)  1 0/6 (0.00%)  0 5/24 (20.83%)  5 3/26 (11.54%)  3
Infections and infestations         
Infection  1  0/3 (0.00%)  0 2/6 (33.33%)  2 2/24 (8.33%)  2 11/26 (42.31%)  11
Infection, Neutropenic fever  1  2/3 (66.67%)  2 5/6 (83.33%)  5 9/24 (37.50%)  9 15/26 (57.69%)  15
Nervous system disorders         
Other Neurologic Disorder  1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/24 (0.00%)  0 1/26 (3.85%)  1
Renal and urinary disorders         
Creatinine increased  1  0/3 (0.00%)  0 0/6 (0.00%)  0 2/24 (8.33%)  2 2/26 (7.69%)  2
GU HEM  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/24 (4.17%)  1 0/26 (0.00%)  0
Alanine aminotransferase increased  1  0/3 (0.00%)  0 0/6 (0.00%)  0 4/24 (16.67%)  4 1/26 (3.85%)  1
Hepatobiliary disorders  1  0/3 (0.00%)  0 1/6 (16.67%)  1 4/24 (16.67%)  4 3/26 (11.54%)  3
Respiratory, thoracic and mediastinal disorders         
Pulmonary Edema  1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/24 (0.00%)  0 1/26 (3.85%)  1
Pulmonary Effusion  1  0/3 (0.00%)  0 0/6 (0.00%)  0 2/24 (8.33%)  2 0/26 (0.00%)  0
Pneumonia  1  0/3 (0.00%)  0 1/6 (16.67%)  1 2/24 (8.33%)  2 3/26 (11.54%)  3
Skin and subcutaneous tissue disorders         
Other Skin Disorder  1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/24 (4.17%)  1 0/26 (0.00%)  0
Rash  1  0/3 (0.00%)  0 0/6 (0.00%)  0 3/24 (12.50%)  3 4/26 (15.38%)  4
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (2.0)
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Muzaffar H. Qazilbash, Professor, Stem Cell Transplantation
Organization: University of Texas (UT) MD Anderson Cancer Center
EMail: CR_Study_Registration@mdanderson.org
Layout table for additonal information
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01079936     History of Changes
Other Study ID Numbers: 2008-0661
NCI-2011-00561 ( Registry Identifier: NCI CTRP )
First Submitted: March 2, 2010
First Posted: March 3, 2010
Results First Submitted: March 31, 2016
Results First Posted: June 6, 2016
Last Update Posted: June 6, 2016