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Phase 1b/2 Safety and Efficacy of APR-246 w/Azacitidine for tx of TP53 Mutant Myeloid Neoplasms

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ClinicalTrials.gov Identifier: NCT03072043
Recruitment Status : Active, not recruiting
First Posted : March 7, 2017
Results First Posted : February 25, 2021
Last Update Posted : May 4, 2021
Sponsor:
Collaborator:
Aprea Therapeutics
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Myelodysplastic Syndrome
Acute Myeloid Leukemia
Myeloproliferative Neoplasm
Chronic Myelomonocytic Leukemia
Interventions Drug: APR-246
Drug: Azacitidine
Enrollment 55
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Phase 1b Dose Level 1 Phase 1B Dose Level 2 Phase 1B Dose Level 3 / Phase 2 MTD
Hide Arm/Group Description Participants treated at level 1: APR-246 50mg/kg lean body weight (LBW) + Azacitidine 75mg/m^2 Participants treated at dose level 2: APR-246 75mg/kg lean body weight (LBW) + Azacitidine 75mg/m^2 Participants treated at dose level 3/Phase 2 MTD : APR-246 100 mg/kg lean body weight (LBW) + Azacitidine 75mg/m^2
Period Title: Overall Study
Started 3 3 49
Completed 3 3 40
Not Completed 0 0 9
Reason Not Completed
Death             0             0             3
Adverse Event             0             0             2
Withdrawal by Subject             0             0             4
Arm/Group Title Phase 1B Dose Level 1 Phase 1B Dos Level 2 Phase 1B Dose Level 3/ MTD Total
Hide Arm/Group Description Participants treated at level 1: APR-246 50mg/kg lean body weight (LBW) + Azacitidine 75mg/m^2 Participants treated at dose level 2: APR-246 75mg/kg lean body weight (LBW) + Azacitidine 75mg/m^2 Participants treated at dose level 3/MTD : APR-246 100 mg/kg lean body weight (LBW) + Azacitidine 75mg/m^2 Total of all reporting groups
Overall Number of Baseline Participants 3 3 49 55
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 49 participants 55 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
1
  33.3%
1
  33.3%
20
  40.8%
22
  40.0%
>=65 years
2
  66.7%
2
  66.7%
29
  59.2%
33
  60.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 49 participants 55 participants
Female
2
  66.7%
3
 100.0%
24
  49.0%
29
  52.7%
Male
1
  33.3%
0
   0.0%
25
  51.0%
26
  47.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 49 participants 55 participants
Hispanic or Latino
0
   0.0%
2
  66.7%
2
   4.1%
4
   7.3%
Not Hispanic or Latino
3
 100.0%
1
  33.3%
45
  91.8%
49
  89.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
2
   4.1%
2
   3.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 49 participants 55 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
2
   4.1%
2
   3.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
2
   4.1%
2
   3.6%
White
2
  66.7%
3
 100.0%
42
  85.7%
47
  85.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
  33.3%
0
   0.0%
3
   6.1%
4
   7.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 3 participants 3 participants 49 participants 55 participants
3 3 49 55
1.Primary Outcome
Title Phase 1b: Maximum Tolerated Dose (MTD)
Hide Description Maximum Tolerated Dose, defined as the dose level below which dose limiting toxicity (DLT) is manifested in ≥33% of the patients or at dose level 3 if DLT is manifested in <33% of the patients.
Time Frame Up to 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase 1b Dose Escalation
Hide Arm/Group Description:

Participants will receive intravenous infusions of APR-246 as a lead-in phase on days -14 to -11 starting at Dose Level 1 prior to starting cycle #1 of combination therapy with azacitidine. Combination therapy will consist of APR-246 on days 1-4 and azacitidine on days 4-10 (or days 4-5 and 8-12) of a 28 day cycle.

APR-246: Phase 1b: Dose escalation of APR-246 via intravenous (IV) infusion, with starting dose of 50 mg/kg lean body weight (LBW). Phase 2: APR-246 at maximum tolerated dose (MTD).

Azacitidine: Azacitidine is administered subcutaneously (SC) or via IV at 75 mg/m^2.

Overall Number of Participants Analyzed 12
Measure Type: Number
Unit of Measure: mg/day
4500
2.Primary Outcome
Title Phase 2: Complete Response (CR) Rate
Hide Description Complete Response Rate as defined by the 2006 International Working Group (IWG) criteria.
Time Frame Up to 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
45 participants were evaluable for response
Arm/Group Title Phase 2: Participants in Dose Level 3/MTD
Hide Arm/Group Description:
All participants who received at least one dose at level 3: 100 mg/kg LBW APR-246 + 75 mg Azacitidine
Overall Number of Participants Analyzed 45
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
53
(38 to 68)
3.Secondary Outcome
Title Phase 2: Duration of Response
Hide Description Duration of response defined as the time between achieving response and progression of disease.
Time Frame Up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
45 participants were evaluable for response.
Arm/Group Title Evaluable Participants
Hide Arm/Group Description:
All evaluable participants
Overall Number of Participants Analyzed 45
Median (Full Range)
Unit of Measure: months
8
(6.5 to 11.2)
4.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS:The length of time from the start of treatment until death by any cause.
Time Frame Up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug
Arm/Group Title Phase 1B Dose Level 1 Phase 1B Dose Level 2 Phase 1B: Dose Level 3 / Phase 2 MTD
Hide Arm/Group Description:
All participants treated at level 1: APR-246 50mg/kg lean body weight (LBW) + Azacitidine 75mg/m^2
All participants treated at dose level 2: APR-246 75mg/kg lean body weight (LBW) + Azacitidine 75mg/m^2
All participants treated at dose level 3/ Phase 2 MTD : APR-246 100 mg/kg lean body weight (LBW) + Azacitidine 75mg/m^2
Overall Number of Participants Analyzed 3 3 49
Median (Full Range)
Unit of Measure: months
14.6
(2.4 to 16.0)
11.6
(6.3 to 13.7)
10.4
(0.7 to 17.9)
5.Secondary Outcome
Title Phase 2: Overall Response Rate
Hide Description Proportion of participants achieving hematological improvement (HI), partial response (PR), complete response (CR), and/or marrow CR (mCR) by the IWG 2006 criteria.
Time Frame Up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
45 participants were evaluable for response
Arm/Group Title All Participants
Hide Arm/Group Description:
All participants
Overall Number of Participants Analyzed 45
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percent of participants
87
(73 to 95)
Time Frame 2 years, 10 months
Adverse Event Reporting Description All Serious Adverse Events are reported, regardless of causality. Serious Adverse Events were reported during screening period and within 100 days of discontinuation of dosing.
 
Arm/Group Title Phase 1b Dose Level 1 Phase 1B Dose Level 2 Phase 1B Dose Level 3/Phase 2 MTD
Hide Arm/Group Description All participants treated at dose level 1: APR-246 50 mg/kg lean body weight (LBW) + Azacitidine 75 mg/m^2 All participants treated at dose level 2: APR-246 75 mg/kg lean body weight (LBW) + Azacitidine 75 mg/m^2 All participants treated at dose level 3 & Phase 2: APR-246 100 mg/kg lean body weight (LBW) + Azacitidine 75 mg/m^2
All-Cause Mortality
Phase 1b Dose Level 1 Phase 1B Dose Level 2 Phase 1B Dose Level 3/Phase 2 MTD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/3 (33.33%)      1/3 (33.33%)      36/49 (73.47%)    
Hide Serious Adverse Events
Phase 1b Dose Level 1 Phase 1B Dose Level 2 Phase 1B Dose Level 3/Phase 2 MTD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/3 (100.00%)      1/3 (33.33%)      30/49 (61.22%)    
Blood and lymphatic system disorders       
Blood and Lymphatic system disorders -Other * 1 [1]  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Febrile neutropenia * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 17/49 (34.69%)  34
Cardiac disorders       
Atrial fibrillation * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Chest pain -cardiac * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Pericardial effusion * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Ear and labyrinth disorders       
Ear and labyrinth disorders -Other * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  2
Gastrointestinal disorders       
Gastrointestinal disorders -Other * 1 [2]  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Vomiting * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
General disorders       
Death NOS * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Infusion related reaction * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Multi organ failure * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Pain * 1 [3]  1/3 (33.33%)  1 0/3 (0.00%)  0 0/49 (0.00%)  0
Infections and infestations       
Abdominal infection * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/49 (0.00%)  0
Bladder infection * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Infection and Infestations - Other * 1  0/3 (0.00%)  0 1/3 (33.33%)  1 7/49 (14.29%)  9
Lung infection * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 7/49 (14.29%)  7
Sepsis * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 5/49 (10.20%)  5
Skin inefection * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Injury, poisoning and procedural complications       
Ankle fracture * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Investigations       
Creatinine increased * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Metabolism and nutrition disorders       
Dehydration * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 3/49 (6.12%)  3
Musculoskeletal and connective tissue disorders       
Bone pain * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Chest wall pain * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Generalized muscle weakness * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 3/49 (6.12%)  3
Nervous system disorders       
Encephalopathy * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Stroke * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Renal and urinary disorders       
Acute kidney injury * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/49 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Adult respiratory distress syndrome * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Aspiration * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Bronchopulmonary hemorrhage * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Respiratory failure * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Respiratory, thoracic and mediastinal disorders - Other * 1  2/3 (66.67%)  2 0/3 (0.00%)  0 3/49 (6.12%)  3
Vascular disorders       
Hypotension * 1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/49 (0.00%)  0
Thromboembolic event * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 3/49 (6.12%)  3
Vascular disorders -Other * 1 [4]  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Vascular disorders - Other * 1 [5]  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
1
Term from vocabulary, CTCAE 4.03
*
Indicates events were collected by non-systematic assessment
[1]
Escherichia coli
[2]
Diverticulitis
[3]
Diffuse body pain
[4]
Deep vein thrombosis
[5]
subdural hematoma
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Phase 1b Dose Level 1 Phase 1B Dose Level 2 Phase 1B Dose Level 3/Phase 2 MTD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/3 (100.00%)      3/3 (100.00%)      47/49 (95.92%)    
Blood and lymphatic system disorders       
Anemia * 1  1/3 (33.33%)  2 0/3 (0.00%)  0 4/49 (8.16%)  5
Blood and lymphatic system disorders - Other * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Bone marrow hypocellular * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Lymph node pain * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Cardiac disorders       
Chest pain - cardiac * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 4/49 (8.16%)  4
Heart palpitations * 1  0/3 (0.00%)  0 1/3 (33.33%)  1 4/49 (8.16%)  4
Sinus tachycardia * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 5/49 (10.20%)  5
Cardiac disorders - Other * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 5/49 (10.20%)  6
Atrial fibrillation * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Ventricular tachycardia * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Sinus bradycardia * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Restrictive cardiomyopathy * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Pericarditis * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Myocardial infarction * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Ear and labyrinth disorders       
Ear pain * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/49 (0.00%)  0
Ear and labyrinth disorders -Other * 1 [1]  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Vertigo * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Endocrine disorders       
Endocrine disorders -other * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  2
Eye disorders       
Blurry vision * 1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/49 (0.00%)  0
Eye disorders - Other * 1 [2]  1/3 (33.33%)  1 0/3 (0.00%)  0 2/49 (4.08%)  2
Dry eye * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Eye pain * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Gastrointestinal disorders       
Nausea * 1  1/3 (33.33%)  2 2/3 (66.67%)  8 32/49 (65.31%)  57
Constipation * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 21/49 (42.86%)  24
Diarrhea * 1  1/3 (33.33%)  1 1/3 (33.33%)  1 15/49 (30.61%)  24
Dry mouth * 1  0/3 (0.00%)  0 2/3 (66.67%)  2 0/49 (0.00%)  0
Enterocolitis * 1  0/3 (0.00%)  0 1/3 (33.33%)  1 1/49 (2.04%)  1
Fecal incontinence * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Mucositis oral * 1  0/3 (0.00%)  0 2/3 (66.67%)  2 8/49 (16.33%)  10
Vomiting * 1  1/3 (33.33%)  1 1/3 (33.33%)  5 22/49 (44.90%)  37
Abdominal pain * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 8/49 (16.33%)  8
Toothache * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  3
Abdominal distension * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Anal pain * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Dental carries * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Dyspepsia * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Esophagitis * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Gastric hemorrhage * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Gastroesophageal reflux disease * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Stomach pain * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Rectal pain * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  2
Rectal hemorrhage * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Oral pain * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 4/49 (8.16%)  6
Oral hemorrhage * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Ileal ulcer * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Hemorrhoids * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Hemorrhoidal hemorrhage * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 3/49 (6.12%)  3
Gastrointestinal disorders -Other * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 3/49 (6.12%)  4
General disorders       
Fever * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 12/49 (24.49%)  16
Flu like symptoms * 1  0/3 (0.00%)  0 1/3 (33.33%)  1 1/49 (2.04%)  1
Gait disturbance * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 7/49 (14.29%)  18
Generalized edema * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 1/49 (2.04%)  4
Pain -Side pain * 1 [3]  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Pain -Hip * 1 [4]  1/3 (33.33%)  1 0/3 (0.00%)  0 4/49 (8.16%)  4
Pain- Jaw * 1 [5]  0/3 (0.00%)  0 1/3 (33.33%)  1 0/49 (0.00%)  0
Pain -Shoulder * 1 [6]  0/3 (0.00%)  0 0/3 (0.00%)  0 4/49 (8.16%)  4
Pain -Muscle * 1 [7]  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Pain -Chest * 1 [8]  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Edema- limbs * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 18/49 (36.73%)  21
Chills * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 8/49 (16.33%)  9
Injection site reaction * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  4
Fatigue * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 23/49 (46.94%)  38
Edema face * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Edema trunk * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Malaise * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 3/49 (6.12%)  4
Diffuse body pain * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Hepatobiliary disorders       
Hepatobiliary disorders - Other * 1 [9]  1/3 (33.33%)  1 0/3 (0.00%)  0 0/49 (0.00%)  0
Port vein thrombosis * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Cholecystitis * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Immune system disorders       
Allergic reaction including pruritis * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Allergic Reaction - swollen tongue * 1 [10]  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Allergic Reaction * 1 [11]  1/3 (33.33%)  1 0/3 (0.00%)  0 1/49 (2.04%)  2
Infections and infestations       
Infections and Infestations - Other * 1  3/3 (100.00%)  3 1/3 (33.33%)  4 12/49 (24.49%)  17
Lung infection * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 4/49 (8.16%)  4
Rhinitis, infective * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Sinusitis * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 2/49 (4.08%)  2
Skin infection * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Tooth infection * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Upper respiratory infection * 1  0/3 (0.00%)  0 1/3 (33.33%)  1 4/49 (8.16%)  4
Urinary tract infection * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 4/49 (8.16%)  4
Eye Infection * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Cecal infection * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Papulopustular rash * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 3/49 (6.12%)  3
Kidney infection * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Injury, poisoning and procedural complications       
Fall * 1  1/3 (33.33%)  1 1/3 (33.33%)  1 7/49 (14.29%)  8
Injury, poisoning and procedural complications - other * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  3
Brusing * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  3
Investigations       
Leukopenia * 1  2/3 (66.67%)  5 2/3 (66.67%)  7 12/49 (24.49%)  14
Alanine aminotransferase increased * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 10/49 (20.41%)  14
Alkaline phosphatase increased * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 4/49 (8.16%)  4
Aspartate aminotransferase increased * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 5/49 (10.20%)  8
Blood bilirubin increased * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 6/49 (12.24%)  11
Creatinine increased * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 8/49 (16.33%)  13
Electrocardiogram QT corrected interval prolonged * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 5/49 (10.20%)  5
Neutrophil count decreased * 1  2/3 (66.67%)  4 3/3 (100.00%)  12 10/49 (20.41%)  27
Hypokalemia * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 7/49 (14.29%)  11
Hypomagnesemia * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 4/49 (8.16%)  4
Weight loss * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Platelet count decreased * 1  1/3 (33.33%)  1 2/3 (66.67%)  6 12/49 (24.49%)  23
Investigations - Other * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  3
Metabolism and nutrition disorders       
Hyperglycemia * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Hypoalbuminemia * 1  1/3 (33.33%)  2 0/3 (0.00%)  0 3/49 (6.12%)  3
Hyponatremia * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 2/49 (4.08%)  3
Anorexia * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 14/49 (28.57%)  15
Dehydration * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Alkalosis * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Metabolism and nutrition disorders - Other * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 5/49 (10.20%)  6
Iron overload * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Hypophosphatemia * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 3/49 (6.12%)  5
Hypernatremia * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Acidosis * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Musculoskeletal and connective tissue disorders       
Back pain * 1  0/3 (0.00%)  0 1/3 (33.33%)  1 9/49 (18.37%)  10
Generalized muscle weakness * 1  2/3 (66.67%)  2 0/3 (0.00%)  0 8/49 (16.33%)  14
Arthralgia * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 7/49 (14.29%)  11
Arthritis * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 5/49 (10.20%)  5
Myalgia * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 5/49 (10.20%)  5
Pain in extremity * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 5/49 (10.20%)  9
Neck pain * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  2
Musculoskeletal and connective tissue disorders - other * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Muscle weakness - lower limb * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 3/49 (6.12%)  3
Bone pain * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 5/49 (10.20%)  6
Nervous system disorders       
Ataxia * 1  2/3 (66.67%)  2 0/3 (0.00%)  0 4/49 (8.16%)  11
Dizziness * 1  1/3 (33.33%)  1 2/3 (66.67%)  5 18/49 (36.73%)  31
Peripheral sensory neuropathy * 1 [12]  0/3 (0.00%)  0 2/3 (66.67%)  8 12/49 (24.49%)  13
Headache * 1  1/3 (33.33%)  2 1/3 (33.33%)  2 14/49 (28.57%)  16
Intracranial hemorrhage * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 1/49 (2.04%)  1
Syncope * 1  0/3 (0.00%)  0 1/3 (33.33%)  1 2/49 (4.08%)  3
Presyncope * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Amnesia * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Tremor * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 10/49 (20.41%)  21
Allodynia * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Nervous system disorders -Other * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 5/49 (10.20%)  6
Concentration impairment * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Dysarthria * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  3
Dysesthesia * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  7
Dysgeusia * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Vasovagal reaction * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Dysphasia * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Somnolence * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  3
Sinus pain * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Paresthesia * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Memory impairment * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/49 (0.00%)  0
Psychiatric disorders       
Anxiety * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 3/49 (6.12%)  3
Insomnia * 1  0/3 (0.00%)  0 1/3 (33.33%)  1 6/49 (12.24%)  7
Confusion * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 5/49 (10.20%)  6
Delirium * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  2
Depression * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Hallucinations * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Renal and urinary disorders       
Dysuria * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 3/49 (6.12%)  3
Urinary incontinence * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 3/49 (6.12%)  3
Urinary frequency * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 4/49 (8.16%)  4
Acute kidney injury * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  3
Chronic kidney disease * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Urinary urgency * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Hematuria * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 3/49 (6.12%)  4
Urinary retention * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  2
Renal calculi * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Renal and urinary disorders - Other * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 3/49 (6.12%)  3
Urinary tract pain * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Reproductive system and breast disorders       
Pelvic pain * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Respiratory, thoracic and mediastinal disorders       
Cough * 1  0/3 (0.00%)  0 1/3 (33.33%)  1 14/49 (28.57%)  19
Allergic rhinitis * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 6/49 (12.24%)  7
Atelectasis * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Wheezing * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  3
Voice alteration * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 3/49 (6.12%)  3
Dyspnea * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 16/49 (32.65%)  17
Epistaxis * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 7/49 (14.29%)  11
Sore throat * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Sinus disorder * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Respiratory, thoracic and mediastinal disorders -Other * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 4/49 (8.16%)  4
Post nasal drip * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Pleuritic pain * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Nasal congestion * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 6/49 (12.24%)  6
Adult respiratory distress syndrome * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Hypoxia * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Pneumonitis * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Skin and subcutaneous tissue disorders       
Skin and subcutaneous tissue disorders - Other * 1  0/3 (0.00%)  0 1/3 (33.33%)  1 10/49 (20.41%)  14
Alopecia * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Bullous dermatitis * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Dry skin * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 4/49 (8.16%)  4
Erythema multiforme * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 5/49 (10.20%)  6
Skin induration * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Rash maculo-papular * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  3
Rash acneiform * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Purpura * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  2
Pruritus * 1  1/3 (33.33%)  1 0/3 (0.00%)  0 12/49 (24.49%)  12
Palmar-plantar ethryodysesthesia syndrome * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Hyperhidrosis * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  2
Vascular disorders       
Flushing * 1  0/3 (0.00%)  0 2/3 (66.67%)  3 1/49 (2.04%)  1
Hematoma * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Vasculitis * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Thromboembolic event * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Superficial thrombophlebitis * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/49 (2.04%)  1
Hypotension * 1  0/3 (0.00%)  0 1/3 (33.33%)  1 4/49 (8.16%)  5
Hypertension * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 4/49 (8.16%)  8
Hot flashes * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/49 (4.08%)  3
1
Term from vocabulary, CTCAE 4.03
*
Indicates events were collected by non-systematic assessment
[1]
Ringing in ears
[2]
Stye in eye
[3]
Generalized right side pain
[4]
Hip pain
[5]
Jaw pain
[6]
Shoulder pain
[7]
muscle pain
[8]
Heartburn
[9]
Hepatomegaly
[10]
Swollen tongue related to urinary tract infection medication
[11]
Platelet transfusion reaction
[12]
facial numbness
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: David Sallman, MD
Organization: Moffitt Cancer Center
Phone: 813-745-6841
EMail: David.Sallman@moffitt.org
Layout table for additonal information
Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT03072043    
Other Study ID Numbers: MCC-18973
First Submitted: March 2, 2017
First Posted: March 7, 2017
Results First Submitted: November 13, 2020
Results First Posted: February 25, 2021
Last Update Posted: May 4, 2021