Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Daunorubicin & Cytarabine +/- Zosuquidar inTreating Older Patients With Newly Diagnosed Acute Myeloid Leukemia or Refractory Anemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00046930
Recruitment Status : Completed
First Posted : January 27, 2003
Results First Posted : September 6, 2010
Last Update Posted : June 26, 2015
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Eli Lilly and Company
Kanisa Pharmaceuticals
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Leukemia
Myelodysplastic Syndromes
Interventions Biological: filgrastim
Biological: sargramostim
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: zosuquidar trihydrochloride
Drug: Placebo
Enrollment 449
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Zosuquidar Placebo
Hide Arm/Group Description Induction treatment with daunorubicin, cytarabine and zosuquidar Induction treatment with daunorubicin, cytarabine and placebo
Period Title: Overall Study
Started 224 225
Completed 212 221
Not Completed 12 4
Reason Not Completed
Ineligible             12             4
Arm/Group Title Zosuquidar Placebo Total
Hide Arm/Group Description Induction treatment with daunorubicin, cytarabine and zosuquidar Induction treatment with daunorubicin, cytarabine and placebo Total of all reporting groups
Overall Number of Baseline Participants 212 221 433
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 212 participants 221 participants 433 participants
69.4  (5.5) 69.2  (5.3) 69.3  (5.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 212 participants 221 participants 433 participants
Female
103
  48.6%
85
  38.5%
188
  43.4%
Male
109
  51.4%
136
  61.5%
245
  56.6%
1.Primary Outcome
Title Overall Survival (OS)
Hide Description Time from randomization to death. Patients alive at last follow-up were censored.
Time Frame Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually thereafter
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible participants, as randomized
Arm/Group Title Zosuquidar Placebo
Hide Arm/Group Description:
Induction treatment with daunorubicin, cytarabine and zosuquidar
Induction treatment with daunorubicin, cytarabine and placebo
Overall Number of Participants Analyzed 212 221
Median (95% Confidence Interval)
Unit of Measure: Months
7.23
(5.62 to 10.58)
9.43
(8.02 to 10.71)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Zosuquidar, Placebo
Comments The study was designed to have 80% power to detect a non-proportional hazards difference in OS at the one-sided 0.025 significance level of 30.2% vs 39.6%, 12.8% vs 27.1% and 7.0% vs 14.0% at 1 years, 2 years, and full information for zosuquidar and placebo, respectively.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.28
Comments [Not Specified]
Method Log Rank
Comments Stratified on age (< 70 vs. >=70) and type of leukemia (de novo AML, secondary RAEB-t, or secondary RAEB AML)
2.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description Time from randomization to the earlier of disease progression or death. Patients alive and progression-free at last follow-up were censored.
Time Frame Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually thereafter
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible participants, as randomized. Patients who had neither documented progression nor death within 3 months of registration without disease evaluation were excluded.
Arm/Group Title Zosuquidar Placebo
Hide Arm/Group Description:
Induction treatment with daunorubicin, cytarabine and zosuquidar
Induction treatment with daunorubicin, cytarabine and placebo
Overall Number of Participants Analyzed 202 211
Median (95% Confidence Interval)
Unit of Measure: Months
3.02
(2.04 to 3.84)
2.04
(1.64 to 3.45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Zosuquidar, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.16
Comments [Not Specified]
Method Log Rank
Comments Stratified on age and type of leukemia
3.Secondary Outcome
Title Response
Hide Description Number of eligible participants in each response category. Categories, based on peripheral blood counts and bone marrow aspirate and biopsy, include complete remission (CR), partial remission (PR), morphologic complete remission (MCR), and relapse.
Time Frame Assessed at the end of induction
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Zosuquidar Placebo
Hide Arm/Group Description:
Induction treatment with daunorubicin, cytarabine and zosuquidar
Induction treatment with daunorubicin, cytarabine and placebo
Overall Number of Participants Analyzed 212 221
Measure Type: Number
Unit of Measure: Participants
Complete Remission 98 96
Morphologic Complete Remission 12 12
Partial Remission 2 0
Relapse 67 90
Unevaluable 33 23
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Zosuquidar, Placebo
Comments Test of difference in the CR (complete remission) rate between the arms.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.617
Comments Test was stratified on age and type of leukemia.
Method Mantel Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
0.77 to 1.65
Estimation Comments Zosuquidar/Placebo
Time Frame Assessed every day until discharged from hospital, then twice weekly until ANC and platelets returned to normal levels. Complete blood counts were obtained monthly for 12 months, then every other month for 12 months.
Adverse Event Reporting Description In addition to lab assessed as above, clinical events were reported via case report forms at the end of Induction, Consolidation I, and Consolidation II. After the end of treatment, forms were collected every 3 months for 2 years, then every 6 months for 3 years. CTCv2 reports were electronically mapped to CTCAE3.
 
Arm/Group Title Zosuquidar Induction Placebo Induction Consolidation I Zosuquidar Consolidation II Placebo Consolidation II
Hide Arm/Group Description Induction treatment with daunorubicin, cytarabine and zosuquidar Induction treatment with daunorubicin, cytarabine and placebo Cytarabine 1500 mg/m2 days 1-6 Consolidation with Daunorubicin, Cytarabine and Zosuquidar Consolidation with Daunorubicin, Cytarabine and Placebo
All-Cause Mortality
Zosuquidar Induction Placebo Induction Consolidation I Zosuquidar Consolidation II Placebo Consolidation II
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Zosuquidar Induction Placebo Induction Consolidation I Zosuquidar Consolidation II Placebo Consolidation II
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   216/219 (98.63%)   218/222 (98.20%)   173/180 (96.11%)   59/59 (100.00%)   69/70 (98.57%) 
Blood and lymphatic system disorders           
Bone Marrow Hypocellularity  1  1/219 (0.46%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Anemia  1  160/219 (73.06%)  152/222 (68.47%)  94/180 (52.22%)  32/59 (54.24%)  37/70 (52.86%) 
Hemolysis  1  1/219 (0.46%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Leukopenia  1  205/219 (93.61%)  211/222 (95.05%)  167/180 (92.78%)  58/59 (98.31%)  66/70 (94.29%) 
Lymphopenia  1  3/219 (1.37%)  5/222 (2.25%)  3/180 (1.67%)  1/59 (1.69%)  2/70 (2.86%) 
Neutropenia  1  200/219 (91.32%)  202/222 (90.99%)  153/180 (85.00%)  48/59 (81.36%)  61/70 (87.14%) 
Thrombocytopenia  1  210/219 (95.89%)  214/222 (96.40%)  169/180 (93.89%)  48/59 (81.36%)  61/70 (87.14%) 
Transfusion: Platelets  1  20/219 (9.13%)  23/222 (10.36%)  20/180 (11.11%)  5/59 (8.47%)  10/70 (14.29%) 
Transfusion: Peripheral Red Blood Cells  1  18/219 (8.22%)  18/222 (8.11%)  15/180 (8.33%)  4/59 (6.78%)  8/70 (11.43%) 
Hematologic - Other  1  2/219 (0.91%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Disseminated Intravascular Coagulation  1  0/219 (0.00%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Thrombotic Microangiopathy  1  0/219 (0.00%)  0/222 (0.00%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
Hemorrhage, GI, Hematemesis  1  1/219 (0.46%)  1/222 (0.45%)  1/180 (0.56%)  0/59 (0.00%)  1/70 (1.43%) 
Hemorrhage, GU, Hematuria  1  3/219 (1.37%)  3/222 (1.35%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
Hemorrhage, Upper Respiratory, Hemoptysis  1  2/219 (0.91%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Hemorrhage Associated with Surgery  1  0/219 (0.00%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Hemorrhage, GI, Melena  1  5/219 (2.28%)  4/222 (1.80%)  0/180 (0.00%)  0/59 (0.00%)  3/70 (4.29%) 
Petechiae  1  7/219 (3.20%)  13/222 (5.86%)  8/180 (4.44%)  0/59 (0.00%)  4/70 (5.71%) 
Hemorrhage, GI, Rectum  1  1/219 (0.46%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Hemorrhage, GU, Vagina  1  0/219 (0.00%)  0/222 (0.00%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
Lymphatics, Other  1  1/219 (0.46%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Cardiac disorders           
Conduction Abnormality  1  1/219 (0.46%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Dysrhythmia  1  1/219 (0.46%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Sinus Bradycardia  1  1/219 (0.46%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Sinus Tachycardia  1  4/219 (1.83%)  5/222 (2.25%)  2/180 (1.11%)  0/59 (0.00%)  0/70 (0.00%) 
Supraventricular Arrhythmia  1  16/219 (7.31%)  8/222 (3.60%)  4/180 (2.22%)  0/59 (0.00%)  0/70 (0.00%) 
Ventricular Arrhythmia  1  0/219 (0.00%)  1/222 (0.45%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
Arrhythmia - Other  1  1/219 (0.46%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Cardiac Ischemia  1  4/219 (1.83%)  2/222 (0.90%)  1/180 (0.56%)  1/59 (1.69%)  0/70 (0.00%) 
Cardiac - Left Ventricular Dysfunction  1  6/219 (2.74%)  8/222 (3.60%)  3/180 (1.67%)  2/59 (3.39%)  1/70 (1.43%) 
Cardiac Troponin I Increased  1  2/219 (0.91%)  2/222 (0.90%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
Cardiac Troponin T Increased  1  2/219 (0.91%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Acute Vascular Leak Syndrome  1  1/219 (0.46%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Hypertension  1  3/219 (1.37%)  7/222 (3.15%)  0/180 (0.00%)  1/59 (1.69%)  0/70 (0.00%) 
Edema  1  6/219 (2.74%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Hypotension  1  16/219 (7.31%)  9/222 (4.05%)  2/180 (1.11%)  1/59 (1.69%)  1/70 (1.43%) 
Cardiac, Other  1  1/219 (0.46%)  1/222 (0.45%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
Endocrine disorders           
Neuroendocrine: ADH Secretion Abnormality  1  1/219 (0.46%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Eye disorders           
Conjunctivitis  1  0/219 (0.00%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Vision - Blurred  1  2/219 (0.91%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Nystagmus  1  0/219 (0.00%)  0/222 (0.00%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
Keratitis  1  0/219 (0.00%)  0/222 (0.00%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
Gastrointestinal disorders           
Anorexia  1  29/219 (13.24%)  20/222 (9.01%)  5/180 (2.78%)  3/59 (5.08%)  4/70 (5.71%) 
Ascites  1  1/219 (0.46%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Colitis  1  5/219 (2.28%)  3/222 (1.35%)  3/180 (1.67%)  1/59 (1.69%)  2/70 (2.86%) 
Constipation  1  0/219 (0.00%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Dehydration  1  4/219 (1.83%)  1/222 (0.45%)  1/180 (0.56%)  0/59 (0.00%)  1/70 (1.43%) 
Heartburn/Dyspepsia  1  1/219 (0.46%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Dysphagia  1  10/219 (4.57%)  2/222 (0.90%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
Ulcer, Gastric  1  1/219 (0.46%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Nausea  1  18/219 (8.22%)  12/222 (5.41%)  3/180 (1.67%)  1/59 (1.69%)  1/70 (1.43%) 
Pancreatitis  1  2/219 (0.91%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Stomatitis  1  19/219 (8.68%)  11/222 (4.95%)  3/180 (1.67%)  3/59 (5.08%)  2/70 (2.86%) 
Typhlitis  1  3/219 (1.37%)  2/222 (0.90%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
Vomiting  1  6/219 (2.74%)  2/222 (0.90%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Diarrhea w/o Prior Colostomy  1  16/219 (7.31%)  13/222 (5.86%)  5/180 (2.78%)  4/59 (6.78%)  4/70 (5.71%) 
Diarrhea w/Colostomy  1  1/219 (0.46%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
GI, Other  1  4/219 (1.83%)  2/222 (0.90%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Pain, Abdomen  1  8/219 (3.65%)  5/222 (2.25%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
Pain, Rectum  1  1/219 (0.46%)  0/222 (0.00%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
General disorders           
Fatigue  1  38/219 (17.35%)  22/222 (9.91%)  8/180 (4.44%)  4/59 (6.78%)  2/70 (2.86%) 
Fever w/o neutropenia  1  1/219 (0.46%)  0/222 (0.00%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
Rigors/Chills  1  2/219 (0.91%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Constitutional, Other  1  0/219 (0.00%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Pain, Other  1  3/219 (1.37%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Hepatobiliary disorders           
Liver Dysfunction/Failure  1  1/219 (0.46%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Hepatic, Other  1  0/219 (0.00%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  1/70 (1.43%) 
Infections and infestations           
Infection, Catheter Related  1  5/219 (2.28%)  8/222 (3.60%)  2/180 (1.11%)  2/59 (3.39%)  3/70 (4.29%) 
Febrile Neutropenia  1  93/219 (42.47%)  82/222 (36.94%)  42/180 (23.33%)  12/59 (20.34%)  15/70 (21.43%) 
Infection w/ Grade 3 or 4 Neutropenia  1  119/219 (54.34%)  121/222 (54.50%)  57/180 (31.67%)  29/59 (49.15%)  26/70 (37.14%) 
Infection w/ Unknown ANC  1  1/219 (0.46%)  3/222 (1.35%)  2/180 (1.11%)  0/59 (0.00%)  0/70 (0.00%) 
Infection without Neutropenia  1  8/219 (3.65%)  7/222 (3.15%)  17/180 (9.44%)  3/59 (5.08%)  4/70 (5.71%) 
Infection, Other  1  2/219 (0.91%)  2/222 (0.90%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Injury, poisoning and procedural complications           
Hemorrhage, Other  1  12/219 (5.48%)  3/222 (1.35%)  4/180 (2.22%)  0/59 (0.00%)  3/70 (4.29%) 
Investigations           
Fibrinogen Decreased  1  0/219 (0.00%)  2/222 (0.90%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Prolonged Partial Thromboplastin Time  1  1/219 (0.46%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
PT (INR) Increased  1  1/219 (0.46%)  2/222 (0.90%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Alkaline Phosphatase Increased  1  2/219 (0.91%)  4/222 (1.80%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
Bilirubin Increased  1  36/219 (16.44%)  31/222 (13.96%)  2/180 (1.11%)  4/59 (6.78%)  1/70 (1.43%) 
Gamma-glutamyl Transpeptidase (GGT) Increased  1  1/219 (0.46%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Hypoalbuminemia  1  1/219 (0.46%)  1/222 (0.45%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
ALT, SGPT Increased  1  5/219 (2.28%)  8/222 (3.60%)  2/180 (1.11%)  0/59 (0.00%)  1/70 (1.43%) 
AST, SGOT Increased  1  8/219 (3.65%)  11/222 (4.95%)  2/180 (1.11%)  0/59 (0.00%)  2/70 (2.86%) 
Acidosis  1  1/219 (0.46%)  3/222 (1.35%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
Alkalosis  1  1/219 (0.46%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Amylase Increased  1  2/219 (0.91%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Bicarbonate, Serum Decreased  1  1/219 (0.46%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Hyperglycemia  1  7/219 (3.20%)  3/222 (1.35%)  2/180 (1.11%)  0/59 (0.00%)  0/70 (0.00%) 
Hyperkalemia  1  0/219 (0.00%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Hypermagnesemia  1  3/219 (1.37%)  2/222 (0.90%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
Hypernatremia  1  2/219 (0.91%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Hyperuricemia  1  4/219 (1.83%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Hypocalcemia  1  17/219 (7.76%)  7/222 (3.15%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Hypoglycemia  1  1/219 (0.46%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Hypokalemia  1  16/219 (7.31%)  12/222 (5.41%)  3/180 (1.67%)  6/59 (10.17%)  1/70 (1.43%) 
Hypomagnesemia  1  1/219 (0.46%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Hyponatremia  1  11/219 (5.02%)  3/222 (1.35%)  3/180 (1.67%)  2/59 (3.39%)  1/70 (1.43%) 
Hypophosphatemia  1  13/219 (5.94%)  4/222 (1.80%)  3/180 (1.67%)  2/59 (3.39%)  1/70 (1.43%) 
Lipase Increased  1  1/219 (0.46%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Ataxia  1  17/219 (7.76%)  2/222 (0.90%)  5/180 (2.78%)  2/59 (3.39%)  0/70 (0.00%) 
Proteinuria  1  1/219 (0.46%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Metabolism and nutrition disorders           
Tumor Lysis Syndrome  1  6/219 (2.74%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Musculoskeletal and connective tissue disorders           
Pain, Joint (Arthralgia)  1  0/219 (0.00%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  1/70 (1.43%) 
Pain, Bone  1  1/219 (0.46%)  1/222 (0.45%)  1/180 (0.56%)  0/59 (0.00%)  1/70 (1.43%) 
Pain, Muscle (Myalgia)  1  1/219 (0.46%)  1/222 (0.45%)  1/180 (0.56%)  0/59 (0.00%)  1/70 (1.43%) 
Nervous system disorders           
Muscle Weakness  1  1/219 (0.46%)  0/222 (0.00%)  0/180 (0.00%)  1/59 (1.69%)  0/70 (0.00%) 
Cerebrovascular Ischemia  1  0/219 (0.00%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Confusion  1  18/219 (8.22%)  3/222 (1.35%)  1/180 (0.56%)  3/59 (5.08%)  0/70 (0.00%) 
Psychosis (Hallucinations/Delusions)  1  24/219 (10.96%)  10/222 (4.50%)  2/180 (1.11%)  0/59 (0.00%)  0/70 (0.00%) 
Somnolence/Depressed Level of Consciousness  1  8/219 (3.65%)  4/222 (1.80%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
Dizziness/Lightheadedness  1  3/219 (1.37%)  0/222 (0.00%)  2/180 (1.11%)  0/59 (0.00%)  1/70 (1.43%) 
Insomnia  1  1/219 (0.46%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Memory Impairment  1  0/219 (0.00%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Mood Alteration: Anxiety/Agitation  1  3/219 (1.37%)  0/222 (0.00%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
Mood Alteration: Depression  1  1/219 (0.46%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Neuropathy, Motor  1  4/219 (1.83%)  2/222 (0.90%)  1/180 (0.56%)  1/59 (1.69%)  1/70 (1.43%) 
Neuropathy, Sensory  1  1/219 (0.46%)  0/222 (0.00%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
Seizure  1  2/219 (0.91%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Speech Impairment  1  4/219 (1.83%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Pyramidal Tract Dysfunction  1  0/219 (0.00%)  0/222 (0.00%)  0/180 (0.00%)  1/59 (1.69%)  0/70 (0.00%) 
Syncope  1  0/219 (0.00%)  0/222 (0.00%)  2/180 (1.11%)  1/59 (1.69%)  0/70 (0.00%) 
Tremor  1  5/219 (2.28%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Neurologic - Other  1  0/219 (0.00%)  0/222 (0.00%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
Pain, Headache  1  1/219 (0.46%)  2/222 (0.90%)  2/180 (1.11%)  0/59 (0.00%)  0/70 (0.00%) 
Renal and urinary disorders           
Renal, Other - Dysuria  1  0/219 (0.00%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Incontinence, Urinary  1  2/219 (0.91%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Renal Failure  1  4/219 (1.83%)  4/222 (1.80%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
Urinary Frequency/Urgency  1  0/219 (0.00%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Urinary Retention  1  0/219 (0.00%)  0/222 (0.00%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
Renal, Other  1  2/219 (0.91%)  1/222 (0.45%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Hemorrhage, Upper Respiratory, Nose  1  12/219 (5.48%)  13/222 (5.86%)  2/180 (1.11%)  2/59 (3.39%)  4/70 (5.71%) 
Pain, Pleura  1  0/219 (0.00%)  2/222 (0.90%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Adult Respiratory Distress Syndrome (ARDS)  1  4/219 (1.83%)  0/222 (0.00%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Dyspnea  1  22/219 (10.05%)  21/222 (9.46%)  3/180 (1.67%)  1/59 (1.69%)  1/70 (1.43%) 
Hypoxia  1  16/219 (7.31%)  12/222 (5.41%)  2/180 (1.11%)  1/59 (1.69%)  0/70 (0.00%) 
Pneumonitis/Pulmonary Infiltrates  1  13/219 (5.94%)  11/222 (4.95%)  2/180 (1.11%)  0/59 (0.00%)  2/70 (2.86%) 
Voice changes/Dysarthria  1  2/219 (0.91%)  2/222 (0.90%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Pulmonary, Other  1  4/219 (1.83%)  4/222 (1.80%)  0/180 (0.00%)  0/59 (0.00%)  0/70 (0.00%) 
Skin and subcutaneous tissue disorders           
Pruritis/itching  1  0/219 (0.00%)  0/222 (0.00%)  1/180 (0.56%)  0/59 (0.00%)  0/70 (0.00%) 
Rash/Desquamation  1  10/219 (4.57%)  4/222 (1.80%)  2/180 (1.11%)  0/59 (0.00%)  1/70 (1.43%) 
Wound, Infectious  1  1/219 (0.46%)  2/222 (0.90%)  2/180 (1.11%)  1/59 (1.69%)  0/70 (0.00%) 
Vascular disorders           
Thrombosis/Embolism  1  1/219 (0.46%)  2/222 (0.90%)  0/180 (0.00%)  1/59 (1.69%)  1/70 (1.43%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Zosuquidar Induction Placebo Induction Consolidation I Zosuquidar Consolidation II Placebo Consolidation II
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   218/219 (99.54%)   221/222 (99.55%)   180/180 (100.00%)   59/59 (100.00%)   70/70 (100.00%) 
Blood and lymphatic system disorders           
Anemia  1  210/219 (95.89%)  215/222 (96.85%)  179/180 (99.44%)  59/59 (100.00%)  70/70 (100.00%) 
Leukopenia  1  171/219 (78.08%)  172/222 (77.48%)  152/180 (84.44%)  56/59 (94.92%)  69/70 (98.57%) 
Neutropenia  1  134/219 (61.19%)  137/222 (61.71%)  116/180 (64.44%)  49/59 (83.05%)  57/70 (81.43%) 
Thrombocytopenia  1  164/219 (74.89%)  183/222 (82.43%)  168/180 (93.33%)  57/59 (96.61%)  67/70 (95.71%) 
Epistaxis  1  13/219 (5.94%)  18/222 (8.11%)  6/180 (3.33%)  4/59 (6.78%)  1/70 (1.43%) 
Petechiae  1  21/219 (9.59%)  16/222 (7.21%)  10/180 (5.56%)  4/59 (6.78%)  2/70 (2.86%) 
Cardiac disorders           
Edema  1  34/219 (15.53%)  46/222 (20.72%)  17/180 (9.44%)  4/59 (6.78%)  7/70 (10.00%) 
Hypotension  1  6/219 (2.74%)  5/222 (2.25%)  6/180 (3.33%)  1/59 (1.69%)  4/70 (5.71%) 
Gastrointestinal disorders           
Anorexia  1  52/219 (23.74%)  41/222 (18.47%)  29/180 (16.11%)  14/59 (23.73%)  11/70 (15.71%) 
Constipation  1  25/219 (11.42%)  22/222 (9.91%)  11/180 (6.11%)  7/59 (11.86%)  8/70 (11.43%) 
Heartburn/Dyspepsia  1  15/219 (6.85%)  13/222 (5.86%)  4/180 (2.22%)  2/59 (3.39%)  0/70 (0.00%) 
Dysphagia  1  17/219 (7.76%)  10/222 (4.50%)  5/180 (2.78%)  1/59 (1.69%)  2/70 (2.86%) 
Nausea  1  89/219 (40.64%)  88/222 (39.64%)  41/180 (22.78%)  17/59 (28.81%)  24/70 (34.29%) 
Stomatitis  1  68/219 (31.05%)  61/222 (27.48%)  29/180 (16.11%)  14/59 (23.73%)  9/70 (12.86%) 
Taste Disturbance  1  21/219 (9.59%)  16/222 (7.21%)  7/180 (3.89%)  4/59 (6.78%)  2/70 (2.86%) 
Vomiting  1  56/219 (25.57%)  39/222 (17.57%)  16/180 (8.89%)  9/59 (15.25%)  8/70 (11.43%) 
Diarrhea w/o Prior Colostomy  1  107/219 (48.86%)  92/222 (41.44%)  37/180 (20.56%)  20/59 (33.90%)  17/70 (24.29%) 
Pain, Abdomen  1  28/219 (12.79%)  17/222 (7.66%)  10/180 (5.56%)  4/59 (6.78%)  5/70 (7.14%) 
General disorders           
Fatigue  1  77/219 (35.16%)  79/222 (35.59%)  78/180 (43.33%)  18/59 (30.51%)  26/70 (37.14%) 
Fever w/o neutropenia  1  8/219 (3.65%)  14/222 (6.31%)  12/180 (6.67%)  4/59 (6.78%)  0/70 (0.00%) 
Rigors/Chills  1  29/219 (13.24%)  31/222 (13.96%)  22/180 (12.22%)  6/59 (10.17%)  14/70 (20.00%) 
Sweating  1  8/219 (3.65%)  15/222 (6.76%)  4/180 (2.22%)  1/59 (1.69%)  3/70 (4.29%) 
Weight Loss  1  15/219 (6.85%)  9/222 (4.05%)  10/180 (5.56%)  4/59 (6.78%)  3/70 (4.29%) 
Investigations           
Alkaline Phosphatase Increased  1  101/219 (46.12%)  95/222 (42.79%)  57/180 (31.67%)  17/59 (28.81%)  15/70 (21.43%) 
Bilirubin Increased  1  117/219 (53.42%)  113/222 (50.90%)  61/180 (33.89%)  12/59 (20.34%)  14/70 (20.00%) 
Hypoalbuminemia  1  13/219 (5.94%)  11/222 (4.95%)  6/180 (3.33%)  4/59 (6.78%)  3/70 (4.29%) 
AST, SGOT Increased  1  97/219 (44.29%)  84/222 (37.84%)  42/180 (23.33%)  19/59 (32.20%)  7/70 (10.00%) 
ALT, SGPT Increased  1  75/219 (34.25%)  92/222 (41.44%)  47/180 (26.11%)  20/59 (33.90%)  12/70 (17.14%) 
Hyperglycemia  1  18/219 (8.22%)  11/222 (4.95%)  11/180 (6.11%)  6/59 (10.17%)  4/70 (5.71%) 
Hypermagnesemia  1  35/219 (15.98%)  22/222 (9.91%)  14/180 (7.78%)  4/59 (6.78%)  3/70 (4.29%) 
Hypocalcemia  1  23/219 (10.50%)  17/222 (7.66%)  9/180 (5.00%)  5/59 (8.47%)  3/70 (4.29%) 
Hypomagnesemia  1  92/219 (42.01%)  82/222 (36.94%)  56/180 (31.11%)  28/59 (47.46%)  22/70 (31.43%) 
Hyponatremia  1  20/219 (9.13%)  16/222 (7.21%)  6/180 (3.33%)  3/59 (5.08%)  1/70 (1.43%) 
Creatinine Increased  1  78/219 (35.62%)  59/222 (26.58%)  23/180 (12.78%)  10/59 (16.95%)  7/70 (10.00%) 
Musculoskeletal and connective tissue disorders           
Pain, Joint (Arthralgia)  1  9/219 (4.11%)  1/222 (0.45%)  7/180 (3.89%)  0/59 (0.00%)  6/70 (8.57%) 
Pain, Bone  1  7/219 (3.20%)  3/222 (1.35%)  8/180 (4.44%)  0/59 (0.00%)  4/70 (5.71%) 
Pain, Muscle (Myalgia)  1  10/219 (4.57%)  9/222 (4.05%)  11/180 (6.11%)  2/59 (3.39%)  6/70 (8.57%) 
Nervous system disorders           
Ataxia  1  11/219 (5.02%)  4/222 (1.80%)  6/180 (3.33%)  2/59 (3.39%)  0/70 (0.00%) 
Confusion  1  17/219 (7.76%)  8/222 (3.60%)  1/180 (0.56%)  1/59 (1.69%)  1/70 (1.43%) 
Dizziness/Lightheadedness  1  19/219 (8.68%)  8/222 (3.60%)  12/180 (6.67%)  1/59 (1.69%)  4/70 (5.71%) 
Tremor  1  29/219 (13.24%)  12/222 (5.41%)  3/180 (1.67%)  5/59 (8.47%)  3/70 (4.29%) 
Pain, Headache  1  22/219 (10.05%)  30/222 (13.51%)  14/180 (7.78%)  3/59 (5.08%)  8/70 (11.43%) 
Respiratory, thoracic and mediastinal disorders           
Cough  1  16/219 (7.31%)  19/222 (8.56%)  6/180 (3.33%)  2/59 (3.39%)  5/70 (7.14%) 
Dyspnea  1  18/219 (8.22%)  13/222 (5.86%)  7/180 (3.89%)  2/59 (3.39%)  6/70 (8.57%) 
Skin and subcutaneous tissue disorders           
Alopecia  1  63/219 (28.77%)  70/222 (31.53%)  74/180 (41.11%)  25/59 (42.37%)  26/70 (37.14%) 
Flushing  1  4/219 (1.83%)  2/222 (0.90%)  5/180 (2.78%)  5/59 (8.47%)  1/70 (1.43%) 
Pruritis/Itching  1  12/219 (5.48%)  11/222 (4.95%)  5/180 (2.78%)  1/59 (1.69%)  1/70 (1.43%) 
Rash/Desquamation  1  48/219 (21.92%)  43/222 (19.37%)  31/180 (17.22%)  12/59 (20.34%)  9/70 (12.86%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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: Study Statistician
Organization: ECOG Statistical Office
Phone: 617-632-3012
Publications of Results:
Cripe LD, Li X, Litzow M, et al.: A randomized, placebo-controlled, double blind trial of the MDR modulator, zosuquidar, during conventional induction and post-remission therapy for Pts > 60 years of age with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS): ECOG 3999. [Abstract] Blood 108 (11): A-423, 2006.
Layout table for additonal information
Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00046930     History of Changes
Obsolete Identifiers: NCT00046046
Other Study ID Numbers: CDR0000257122
E3999 ( Other Identifier: Eastern Cooperative Oncology Group )
U10CA021115 ( U.S. NIH Grant/Contract )
First Submitted: October 3, 2002
First Posted: January 27, 2003
Results First Submitted: August 17, 2010
Results First Posted: September 6, 2010
Last Update Posted: June 26, 2015