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Trial record 1 of 1 for:    CA180-399
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Study of Dasatinib vs Imatinib in Patients With Chronic Myeloid Leukemia (CML) Who Did Not Have Favorable Response to Imatinib (DASCERN)

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ClinicalTrials.gov Identifier: NCT01593254
Recruitment Status : Active, not recruiting
First Posted : May 8, 2012
Results First Posted : April 11, 2019
Last Update Posted : April 11, 2019
Sponsor:
Collaborators:
ICON Clinical Research
PPD
Molecular MD
MultiPharma
Q2 Solutions
Donald E. Morisky
MD Anderson Symptom Inventory (MDASI-CML)
OBiS, Inc
Steering Committee
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Chronic Phase Chronic Myeloid Leukemia
Interventions Drug: Imatinib
Drug: Dasatinib
Enrollment 262
Recruitment Details  
Pre-assignment Details 262 were enrolled. 260 were randomized. 2 were not randomized due to failure to meet inclusion/exclusion criteria
Arm/Group Title Arm 1: Imatinib (≥400 mg) Arm 2: Dasatinib (100 mg)
Hide Arm/Group Description Imatinib ≥400 mg tablets by mouth once daily (QD) or twice daily (BID) up to 60 months. Participants randomized to Imatinib that crossover to Dasatinib (n= 42); Participants randomized to Imatinib, no crossover (n = 44) Dasatinib 100 mg tablet by mouth QD up to 60 months
Period Title: Treatment Period
Started [1] 86 174
Crossed Over to Dasatinib 42 0
Completed [2] 72 143
Not Completed 14 31
Reason Not Completed
Treatment Failure             1             2
Pregnancy             0             1
Poor/Non-Compliance             2             1
Maximum clinical benefit             1             0
Subject withdrew consent             0             5
Subject Request to Discontinue             1             1
AE unrelated to Study Drug             0             1
Death             2             1
Study Drug Toxicity             3             9
Disease Progression             1             6
Did Not Achieve RCC             0             1
Patient Refused to Return             0             1
No Response             1             0
T315I MUTATION             0             1
Investigator Decision             2             1
[1]
Started = Started Treatment Period
[2]
Completed = Continuing in Treatment Period
Period Title: Follow-Up Period
Started [1] 14 28
Completed [2] 11 17
Not Completed 3 11
Reason Not Completed
Withdrawal by Subject             0             2
Non-Compliance             1             0
Death             2             2
Subject request to Discontinue             0             1
Pregnancy             0             1
Study Drug Toxicity             0             1
Patient refused to return             0             1
Fundus Hemorrhage             0             1
Disease Progression             0             1
Study Drug Side Effects             0             1
[1]
Started Follow-Up Period
[2]
Continuing in the Follow-Up Period
Arm/Group Title Arm 1: Imatinib (≥400 mg) Arm 2: Dasatinib (100 mg) Total
Hide Arm/Group Description Imatinib ≥400 mg tablets by mouth once daily (QD) or twice daily (BID) up to 60 months. Participants randomized to Imatinib that crossover to Dasatinib (n= 42); Participants randomized to Imatinib, no crossover (n = 44) Dasatinib 100 mg tablet by mouth QD up to 60 months Total of all reporting groups
Overall Number of Baseline Participants 86 174 260
Hide Baseline Analysis Population Description
All Randomized participants
Age, Continuous   [1] 
Median (Full Range)
Unit of measure:  Years
Number Analyzed 86 participants 174 participants 260 participants
39.5
(18 to 73)
35.0
(18 to 82)
37.0
(18 to 82)
[1]
Measure Analysis Population Description: All Randomized Participants
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 86 participants 174 participants 260 participants
Female
16
  18.6%
41
  23.6%
57
  21.9%
Male
70
  81.4%
133
  76.4%
203
  78.1%
[1]
Measure Analysis Population Description: All Randomized Participants
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 86 participants 174 participants 260 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
86
 100.0%
174
 100.0%
260
 100.0%
[1]
Measure Analysis Population Description: All Randomized Participants
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 86 participants 174 participants 260 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
63
  73.3%
127
  73.0%
190
  73.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
   3.5%
4
   2.3%
7
   2.7%
White
15
  17.4%
36
  20.7%
51
  19.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
5
   5.8%
7
   4.0%
12
   4.6%
[1]
Measure Analysis Population Description: All Randomized Participants
1.Primary Outcome
Title Percentage of Patients Achieving Major Molecular Response (MMR) After 12 Months of CML Treatment
Hide Description

Major Molecular Response, is defined as a 3-log reduction in BCR-ABL transcripts from the standardized baseline, which represents 100% on the international scale, so a 3-log reduction is fixed at 0.1% for MMR; N/A = not applicable. 95% CI is Clopper-Pearson(Exact) two-sided 95% confidence intervals.

P-value is based on Cochran-Mantel-Haenszel (CMH) test stratified by Sokal score(high, intermediate, low, and unknown) and time between 3 month molecular analysis and randomization (<=4 weeks vs >4 weeks). Month 12 is calculated fro

Time Frame At 12 months after Day 1 initiation of 1st line treatment with imatinib or imatinib at any dose, after less than optimal response to first-line imatinib.
Hide Outcome Measure Data
Hide Analysis Population Description
All Randomized Participants
Arm/Group Title Arm 1: Imatinib (≥400 mg) Arm 2: Dasatinib (100 mg)
Hide Arm/Group Description:
Imatinib ≥400 mg tablets by mouth once daily (QD) or twice daily (BID) up to 60 months. Participants randomized to Imatinib that crossover to Dasatinib (n= 42); Participants randomized to Imatinib, no crossover (n = 44)
Dasatinib 100 mg tablet by mouth QD up to 60 months
Overall Number of Participants Analyzed 86 174
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Patients
12.8
(6.6 to 21.7)
28.7
(22.1 to 36.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm 1: Imatinib (≥400 mg), Arm 2: Dasatinib (100 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
2.Secondary Outcome
Title Median Time to Major Molecular Response (MMR)
Hide Description Time to MMR is how fast patients achieve optimal response. It is the time between randomization date and first date that MMR criteria are satisfied.
Time Frame Up to 10 years
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Time to Molecular Response (MR)^4.5
Hide Description Time to MR^4.5 is how fast patients achieve a deeper response. It is the time between randomization date and first date that MR^4.5 criteria are satisfied.
Time Frame Up to 10 years
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS is how long patients are likely to live without progression of their disease. It is the time from randomization date to progression date or death date, whichever occurs first.
Time Frame Up to 10 years
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS is how long patients are likely to remain alive. It is the time from randomization date to death date.
Time Frame Up to 10 years
Outcome Measure Data Not Reported
Time Frame From first dose date up to 30 days after last dose of study therapy. Assessed from Sept. 2012 to Nov. 2017 (approximately 62 months)
Adverse Event Reporting Description 3 patients allocated to dasatinib decided to withdraw their consent prior to start taking the study drug and were never exposed. This is why the safety population is 171 in dasatinib arm even though 174 were randomized to Dasatinib
 
Arm/Group Title Randomized to Dasatinib Rand to Imatinib(Crossover to Dasatinib) Randomized to Imatinib (No Crossover)
Hide Arm/Group Description Dasatinib 100 mg tablet by mouth QD up to 60 months Imatinib ≥400 mg tablets by mouth once daily (QD) or twice daily (BID) up to 60 months Imatinib ≥400 mg tablets by mouth once daily (QD) or twice daily (BID) up to 60 months
All-Cause Mortality
Randomized to Dasatinib Rand to Imatinib(Crossover to Dasatinib) Randomized to Imatinib (No Crossover)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/171 (2.92%)   3/42 (7.14%)   1/44 (2.27%) 
Show Serious Adverse Events Hide Serious Adverse Events
Randomized to Dasatinib Rand to Imatinib(Crossover to Dasatinib) Randomized to Imatinib (No Crossover)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   28/171 (16.37%)   7/42 (16.67%)   5/44 (11.36%) 
Blood and lymphatic system disorders       
Anaemia  1  1/171 (0.58%)  1/42 (2.38%)  0/44 (0.00%) 
Lymphadenitis  1  1/171 (0.58%)  0/42 (0.00%)  0/44 (0.00%) 
Neutropenia  1  0/171 (0.00%)  1/42 (2.38%)  0/44 (0.00%) 
Pancytopenia  1  0/171 (0.00%)  1/42 (2.38%)  0/44 (0.00%) 
Thrombocytopenia  1  2/171 (1.17%)  1/42 (2.38%)  0/44 (0.00%) 
Cardiac disorders       
Coronary artery disease  1  0/171 (0.00%)  1/42 (2.38%)  0/44 (0.00%) 
Eye disorders       
Diabetic retinopathy  1  0/171 (0.00%)  0/42 (0.00%)  1/44 (2.27%) 
Periorbital oedema  1  0/171 (0.00%)  1/42 (2.38%)  0/44 (0.00%) 
Visual impairment  1  0/171 (0.00%)  0/42 (0.00%)  1/44 (2.27%) 
Vitreous haemorrhage  1  1/171 (0.58%)  0/42 (0.00%)  0/44 (0.00%) 
Gastrointestinal disorders       
Diarrhoea  1  1/171 (0.58%)  0/42 (0.00%)  1/44 (2.27%) 
Gingival cyst  1  1/171 (0.58%)  0/42 (0.00%)  0/44 (0.00%) 
Haemorrhoids  1  2/171 (1.17%)  0/42 (0.00%)  0/44 (0.00%) 
Salivary gland cyst  1  1/171 (0.58%)  0/42 (0.00%)  0/44 (0.00%) 
General disorders       
Adverse event  1  1/171 (0.58%)  0/42 (0.00%)  0/44 (0.00%) 
Chest pain  1  1/171 (0.58%)  0/42 (0.00%)  0/44 (0.00%) 
Hepatobiliary disorders       
Cholecystitis  1  1/171 (0.58%)  0/42 (0.00%)  0/44 (0.00%) 
Infections and infestations       
Anal abscess  1  1/171 (0.58%)  1/42 (2.38%)  0/44 (0.00%) 
Appendicitis  1  2/171 (1.17%)  0/42 (0.00%)  0/44 (0.00%) 
Dengue fever  1  1/171 (0.58%)  0/42 (0.00%)  0/44 (0.00%) 
Erysipelas  1  1/171 (0.58%)  0/42 (0.00%)  0/44 (0.00%) 
Folliculitis  1  0/171 (0.00%)  1/42 (2.38%)  0/44 (0.00%) 
Lung infection  1  3/171 (1.75%)  1/42 (2.38%)  0/44 (0.00%) 
Lymphangitis  1  1/171 (0.58%)  0/42 (0.00%)  0/44 (0.00%) 
Pneumonia  1  1/171 (0.58%)  2/42 (4.76%)  0/44 (0.00%) 
Pulmonary sepsis  1  0/171 (0.00%)  1/42 (2.38%)  0/44 (0.00%) 
Tracheobronchitis  1  0/171 (0.00%)  1/42 (2.38%)  0/44 (0.00%) 
Upper respiratory tract infection  1  0/171 (0.00%)  1/42 (2.38%)  0/44 (0.00%) 
Injury, poisoning and procedural complications       
Limb injury  1  1/171 (0.58%)  0/42 (0.00%)  0/44 (0.00%) 
Paternal exposure during pregnancy  1  1/171 (0.58%)  0/42 (0.00%)  0/44 (0.00%) 
Spinal fracture  1  1/171 (0.58%)  0/42 (0.00%)  0/44 (0.00%) 
Investigations       
Platelet count decreased  1  0/171 (0.00%)  1/42 (2.38%)  0/44 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  1/171 (0.58%)  0/42 (0.00%)  0/44 (0.00%) 
Musculoskeletal chest pain  1  0/171 (0.00%)  1/42 (2.38%)  0/44 (0.00%) 
Myalgia  1  0/171 (0.00%)  0/42 (0.00%)  1/44 (2.27%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Central nervous system leukaemia  1  1/171 (0.58%)  0/42 (0.00%)  0/44 (0.00%) 
Chronic myeloid leukaemia  1  0/171 (0.00%)  0/42 (0.00%)  1/44 (2.27%) 
Chronic myeloid leukaemia transformation  1  1/171 (0.58%)  0/42 (0.00%)  0/44 (0.00%) 
Nervous system disorders       
Headache  1  1/171 (0.58%)  0/42 (0.00%)  0/44 (0.00%) 
Ischaemic stroke  1  0/171 (0.00%)  1/42 (2.38%)  0/44 (0.00%) 
Renal and urinary disorders       
Acute kidney injury  1  1/171 (0.58%)  0/42 (0.00%)  0/44 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Pleural effusion  1  2/171 (1.17%)  3/42 (7.14%)  0/44 (0.00%) 
Respiratory failure  1  0/171 (0.00%)  1/42 (2.38%)  0/44 (0.00%) 
Skin and subcutaneous tissue disorders       
Rash  1  0/171 (0.00%)  0/42 (0.00%)  1/44 (2.27%) 
Surgical and medical procedures       
Hysterectomy  1  1/171 (0.58%)  0/42 (0.00%)  0/44 (0.00%) 
Vascular disorders       
Hypertension  1  1/171 (0.58%)  0/42 (0.00%)  0/44 (0.00%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Randomized to Dasatinib Rand to Imatinib(Crossover to Dasatinib) Randomized to Imatinib (No Crossover)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   151/171 (88.30%)   36/42 (85.71%)   38/44 (86.36%) 
Blood and lymphatic system disorders       
Anaemia  1  44/171 (25.73%)  13/42 (30.95%)  10/44 (22.73%) 
Leukopenia  1  11/171 (6.43%)  5/42 (11.90%)  5/44 (11.36%) 
Neutropenia  1  37/171 (21.64%)  17/42 (40.48%)  7/44 (15.91%) 
Thrombocytopenia  1  39/171 (22.81%)  11/42 (26.19%)  4/44 (9.09%) 
Eye disorders       
Eyelid oedema  1  2/171 (1.17%)  5/42 (11.90%)  3/44 (6.82%) 
Gastrointestinal disorders       
Abdominal pain  1  9/171 (5.26%)  1/42 (2.38%)  2/44 (4.55%) 
Abdominal pain upper  1  13/171 (7.60%)  3/42 (7.14%)  2/44 (4.55%) 
Diarrhoea  1  28/171 (16.37%)  6/42 (14.29%)  7/44 (15.91%) 
Nausea  1  15/171 (8.77%)  2/42 (4.76%)  5/44 (11.36%) 
Vomiting  1  7/171 (4.09%)  2/42 (4.76%)  3/44 (6.82%) 
General disorders       
Asthenia  1  10/171 (5.85%)  1/42 (2.38%)  1/44 (2.27%) 
Fatigue  1  7/171 (4.09%)  1/42 (2.38%)  4/44 (9.09%) 
Pyrexia  1  15/171 (8.77%)  7/42 (16.67%)  3/44 (6.82%) 
Infections and infestations       
Influenza  1  9/171 (5.26%)  0/42 (0.00%)  1/44 (2.27%) 
Nasopharyngitis  1  12/171 (7.02%)  6/42 (14.29%)  3/44 (6.82%) 
Upper respiratory tract infection  1  22/171 (12.87%)  10/42 (23.81%)  6/44 (13.64%) 
Investigations       
Alanine aminotransferase increased  1  12/171 (7.02%)  4/42 (9.52%)  4/44 (9.09%) 
Aspartate aminotransferase increased  1  13/171 (7.60%)  4/42 (9.52%)  4/44 (9.09%) 
Blood bilirubin increased  1  11/171 (6.43%)  2/42 (4.76%)  1/44 (2.27%) 
Blood cholesterol increased  1  10/171 (5.85%)  1/42 (2.38%)  0/44 (0.00%) 
Blood creatine phosphokinase increased  1  13/171 (7.60%)  4/42 (9.52%)  4/44 (9.09%) 
Blood lactate dehydrogenase increased  1  13/171 (7.60%)  1/42 (2.38%)  0/44 (0.00%) 
Gamma-glutamyltransferase increased  1  10/171 (5.85%)  1/42 (2.38%)  1/44 (2.27%) 
Haemoglobin decreased  1  11/171 (6.43%)  4/42 (9.52%)  2/44 (4.55%) 
High density lipoprotein decreased  1  9/171 (5.26%)  1/42 (2.38%)  1/44 (2.27%) 
Neutrophil count decreased  1  21/171 (12.28%)  10/42 (23.81%)  7/44 (15.91%) 
Platelet count decreased  1  35/171 (20.47%)  11/42 (26.19%)  10/44 (22.73%) 
Red blood cell count decreased  1  5/171 (2.92%)  3/42 (7.14%)  2/44 (4.55%) 
White blood cell count decreased  1  21/171 (12.28%)  9/42 (21.43%)  6/44 (13.64%) 
Metabolism and nutrition disorders       
Hypertriglyceridaemia  1  10/171 (5.85%)  1/42 (2.38%)  2/44 (4.55%) 
Hyperuricaemia  1  6/171 (3.51%)  0/42 (0.00%)  4/44 (9.09%) 
Hypocalcaemia  1  6/171 (3.51%)  4/42 (9.52%)  4/44 (9.09%) 
Hypophosphataemia  1  21/171 (12.28%)  5/42 (11.90%)  8/44 (18.18%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  6/171 (3.51%)  5/42 (11.90%)  1/44 (2.27%) 
Back pain  1  5/171 (2.92%)  0/42 (0.00%)  3/44 (6.82%) 
Muscle spasms  1  2/171 (1.17%)  3/42 (7.14%)  7/44 (15.91%) 
Myalgia  1  10/171 (5.85%)  1/42 (2.38%)  0/44 (0.00%) 
Pain in extremity  1  8/171 (4.68%)  2/42 (4.76%)  5/44 (11.36%) 
Nervous system disorders       
Dizziness  1  9/171 (5.26%)  4/42 (9.52%)  2/44 (4.55%) 
Headache  1  36/171 (21.05%)  5/42 (11.90%)  3/44 (6.82%) 
Psychiatric disorders       
Anxiety  1  2/171 (1.17%)  1/42 (2.38%)  3/44 (6.82%) 
Depression  1  0/171 (0.00%)  0/42 (0.00%)  3/44 (6.82%) 
Insomnia  1  4/171 (2.34%)  3/42 (7.14%)  4/44 (9.09%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  15/171 (8.77%)  2/42 (4.76%)  1/44 (2.27%) 
Dyspnoea  1  9/171 (5.26%)  5/42 (11.90%)  2/44 (4.55%) 
Pleural effusion  1  10/171 (5.85%)  1/42 (2.38%)  0/44 (0.00%) 
Skin and subcutaneous tissue disorders       
Rash  1  17/171 (9.94%)  4/42 (9.52%)  6/44 (13.64%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
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.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
Phone: Please Email:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01593254     History of Changes
Other Study ID Numbers: CA180-399
2011-006181-41 ( EudraCT Number )
First Submitted: May 4, 2012
First Posted: May 8, 2012
Results First Submitted: November 8, 2018
Results First Posted: April 11, 2019
Last Update Posted: April 11, 2019