A Study of Dasatinib vs. High-Dose Imatinib (600 mg) in Patients With Chronic Phase Chronic Myeloid Leukemia (CML) Who Failed to Achieve Complete Cytogenetic Response After 3-18 Months of Imatinib Therapy

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00362466
• Collaborator: (none)
• Enrollment: 3
• Locations: 45
• Arms: 2
• Duration (Months): 14
• Patients Per Site: 0.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this clinical research study is to compare the rate of complete cytogenetic response of dasatinib to imatinib therapy at 6 months after randomization in chronic phase CML patients. The safety of this treatment will also be studied.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: Dasatinib; Drug: Imatinib	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Randomized Phase III Study of Dasatinib vs. High-Dose (600 mg) Imatinib Mesylate in the Treatment of Subjects With Chronic Phase Philadelphia Chromosome-Positive Chronic Myeloid Leukemia Who Are Imatinib Failures or Who Have Had a Suboptimal Response After 3-18 Months of Therapy With 400 mg Imatinib
• Study Start Date: Apr 1, 2007
• Actual Primary Completion Date: Jun 1, 2008
• Actual Study Completion Date: Jun 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: A 50-180 mg once daily (QD)	Drug: Dasatinib; Tablets, Oral, Once daily, 5-7 years; Other Names: Sprycel®
Active Comparator: B 200-800 mg QD	Drug: Imatinib; Tablets, Oral, Once daily, 5-7 years

Outcome Measures

Primary Outcome Measures

1. Complete Cytogenetic Response (CCyR) Rate at Month 6 [Month 6]

   Cytogenetic Response (CyR) is based on the prevalence of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a bone marrow sample. The criteria for CCyR is 0% Ph+ metaphases among cells in a bone marrow sample.

Secondary Outcome Measures

1. Major Molecular Response (MMR) Rates [Month 3, Month 6, Month 12, Month 24 and Month 36]

   MMR is defined as a 3-log reduction in BCR-ABL gene transcripts from a standardized baseline. Reductions in BCR-ABL transcripts on logarithmic scale are calculated based on the absolute values expressed as percent of ratio of BCR-ABL gene transcripts to the control gene. In this study,ABL was used as the control gene.

2. CCyR Rates [Month 3, Month 12, Month 24 and Month 36]

   CyR is based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample. The criteria for CCyR is 0% Ph+ metaphases among cells in a bone marrow sample.

3. Estimate Time to MMR and CCyR [throughout the study]

   Time to MMR is defined as the time from first treatment dose until measurement criteria are first met for MMR. Time to MMR is computed only for subjects who achieved a MMR. Time to CCyR is defined as the time from first treatment dose until measurement criteria are first met for CCyR. Time to CCyR is computed only for subjects who achieved a CCyR.

4. Progression Free Survival (PFS) [at 36 months]

   PFS=time from randomization until progression or death. Participants who died without progression=progression on date of death. Participants who neither progressed nor died were censored on date of last hematologic assessment. Participants who did not receive study treatment and neither progressed nor died were censored on date of randomization.

5. Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs [From 2 weeks prior to randomization through Month 36. At least every 4 weeks until all study-related toxicities resolve to baseline, stabilize, or are deemed irreversible.]

   An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a patient or clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.

6. Duration of CCyR and MMR [Throughout the study]

   Duration of CCyR computed for subjects with CCyR as best response; measured from time the criteria are first met for CCyR until date of progression or death. Duration of MMR computed for subjects with MMR as best response; measured from time the criteria are first met for MMR until date the MMR was first lost, disease progression or death.

7. Best MMR Rates [throughout study]

   MMR is defined as a 3-log reduction in BCR-ABL gene transcripts from a standardized baseline. Reductions in BCR-ABL transcripts on logarithmic scale are calculated based on the absolute values expressed as % of ratio of BCR-ABL gene transcripts to the control gene. In this study, ABL was used as the control gene.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men and women ≥18 years diagnosed with Chronic Phase Philadelphia chromosome positive (CP Ph+) CML who have failed to achieve CCyR after 3-18 months of therapy with imatinib 400 mg

• Treatment initiation with imatinib 400 mg within 6 months of initial CML diagnosis

• Able to tolerate chronic administration of imatinib at the highest dose (400-600 mg) the subject has received in the past

• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2

• Adequate hepatic and renal function

Exclusion Criteria:

• Eligible and willing to undergo immediate autologous/allogeneic stem cell transplant

• Previous diagnosis of accelerated/blast crisis CML

• Subjects with clonal evolution in Ph+ cells observed in ≥2 metaphases

• Previous documentation of T315I mutation

• Uncontrolled or significant cardiovascular disease

• Serious uncontrolled medical disorder/active infection

• History of significant bleeding disorder unrelated to CML

• Intolerance to imatinib ≥400 mg

• Concurrent malignancies other than CML

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dr. Marshall Schreeder	Huntsville	Alabama	United States	35805
2	Local Institution	Little Rock	Arkansas	United States	72205
3	Local Institution	Alhambra	California	United States	91801
4	Local Institution	Anaheim	California	United States	92801
5	Local Institution	Beverly Hills	California	United States	90211
6	Local Institution	Fullerton	California	United States	92835
7	Local Institution	La Jolla	California	United States	92093
8	Local Institution	La Verne	California	United States	91750
9	Local Institution	Long Beach	California	United States	90813
10	Local Institution	Los Angeles	California	United States	90033
11	Local Institution	Los Angeles	California	United States	90048
12	Local Institution	Los Angeles	California	United States	90095
13	Local Institution	Northridge	California	United States	91325
14	Local Institution	Oxnard	California	United States	93030
15	Local Institution	Redondo Beach	California	United States	90277
16	Local Institution	San Francisco	California	United States	94143
17	Local Institution	Santa Maria	California	United States	93454
18	Local Institution	Stanford	California	United States	94305
19	Local Institution	Aurora	Colorado	United States	80045
20	Local Institution	Jacksonville	Florida	United States	32207
21	Local Institution	Jacksonville	Florida	United States	32209
22	M.D. Anderson Cancer Center Orlando	Orlando	Florida	United States	32806
23	Local Institution	Pembroke Pines	Florida	United States	33028
24	Local Institution	Chicago	Illinois	United States	60637
25	Local Institution	Indianapolis	Indiana	United States	46202
26	Local Institution	Kansas City	Kansas	United States	66160
27	Local Institution	Hazard	Kentucky	United States	41701
28	Local Institution	Ann Arbor	Michigan	United States	48109
29	Local Institution	Rochester	Minnesota	United States	55905
30	Local Institution	St. Louis	Missouri	United States	63110
31	Local Institution	Omaha	Nebraska	United States	68114
32	Local Institution	Las Vegas	Nevada	United States	89135
33	Local Institution	Hackensack	New Jersey	United States	07601
34	Local Institution	Buffalo	New York	United States	14263
35	New York Presbyterian Hospital	New York	New York	United States	10021
36	New York Medical College	Valhalla	New York	United States	10595
37	Local Institution	Durham	North Carolina	United States	27710
38	Local Institution	Cleveland	Ohio	United States	44195
39	Local Institution	Oklahoma City	Oklahoma	United States	73112
40	Local Institution	Tulsa	Oklahoma	United States	74136
41	Local Institution	Baltimore	Pennsylvania	United States	21229
42	Local Institution	Pittsburgh	Pennsylvania	United States	15232
43	Santee Hematology/Oncology	Sumter	South Carolina	United States	29150
44	Local Institution	Dallas	Texas	United States	75390
45	Local Institution	Houston	Texas	United States	77030

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00362466
• Other Study ID Numbers: CA180-044
• First Posted: Aug 10, 2006
• Last Update Posted: Nov 20, 2009
• Last Verified: Nov 1, 2009

• Keywords provided by , ,: Leukemia (chronic myeloid leukemia - chronic phase)
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Imatinib Mesylate; Dasatinib

Study Results

Participant Flow

Recruitment Details	A total of 156 subjects were to be enrolled; however, the attempts were unsuccessful and the study was closed after 3 subjects were enrolled. A fourth subject underwent screening, but was not randomized since the subject did not meet the inclusion criteria.

Arm/Group Title	Dasatinib	Imatinib
Arm/Group Description	100 mg once daily (QD)	600 mg QD
Period Title: Overall Study
STARTED	2	1
COMPLETED	2	1
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Dasatinib	Imatinib	Total
Arm/Group Description	100 mg QD	600 mg QD	Total of all reporting groups
Overall Participants	2	1	3
Age (Number) [Number]
30- to 39-years-old	1 50%	0 0%	1 33.3%
40- to 49-years-old	1 50%	0 0%	1 33.3%
50- to 59-years-old	0 0%	1 100%	1 33.3%
Sex: Female, Male (Count of Participants)
Female	0 0%	1 100%	1 33.3%
Male	2 100%	0 0%	2 66.7%
Race/Ethnicity, Customized (participants) [Number]
White	2 100%	1 100%	3 100%

Outcome Measures

1. Primary Outcome

Title	Complete Cytogenetic Response (CCyR) Rate at Month 6
Description	Cytogenetic Response (CyR) is based on the prevalence of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a bone marrow sample. The criteria for CCyR is 0% Ph+ metaphases among cells in a bone marrow sample.
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

This analysis was not done. This study was terminated due to insufficient enrollment.

Arm/Group Title	Dasatinib	Imatinib
Arm/Group Description	100 mg QD	600 mg QD
Measure Participants	0	0

2. Secondary Outcome

Title	Major Molecular Response (MMR) Rates
Description	MMR is defined as a 3-log reduction in BCR-ABL gene transcripts from a standardized baseline. Reductions in BCR-ABL transcripts on logarithmic scale are calculated based on the absolute values expressed as percent of ratio of BCR-ABL gene transcripts to the control gene. In this study,ABL was used as the control gene.
Time Frame	Month 3, Month 6, Month 12, Month 24 and Month 36

Outcome Measure Data

Analysis Population Description

This analysis was not done. This study was terminated due to insufficient enrollment.

Arm/Group Title	Dasatinib	Imatinib
Arm/Group Description	100 mg QD	600 mg QD
Measure Participants	0	0

3. Secondary Outcome

Title	CCyR Rates
Description	CyR is based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample. The criteria for CCyR is 0% Ph+ metaphases among cells in a bone marrow sample.
Time Frame	Month 3, Month 12, Month 24 and Month 36

Outcome Measure Data

Analysis Population Description

This analysis was not done. This study was terminated due to insufficient enrollment.

Arm/Group Title	Dasatinib	Imatinib
Arm/Group Description	100 mg QD	600 mg QD
Measure Participants	0	0

4. Secondary Outcome

Title	Estimate Time to MMR and CCyR
Description	Time to MMR is defined as the time from first treatment dose until measurement criteria are first met for MMR. Time to MMR is computed only for subjects who achieved a MMR. Time to CCyR is defined as the time from first treatment dose until measurement criteria are first met for CCyR. Time to CCyR is computed only for subjects who achieved a CCyR.
Time Frame	throughout the study

Outcome Measure Data

Analysis Population Description

This analysis was not done. This study was terminated due to insufficient enrollment.

Arm/Group Title	Dasatinib	Imatinib
Arm/Group Description	100 mg QD	600 mg QD
Measure Participants	0	0

5. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS=time from randomization until progression or death. Participants who died without progression=progression on date of death. Participants who neither progressed nor died were censored on date of last hematologic assessment. Participants who did not receive study treatment and neither progressed nor died were censored on date of randomization.
Time Frame	at 36 months

Outcome Measure Data

Analysis Population Description

This analysis was not done. This study was terminated due to insufficient enrollment.

Arm/Group Title	Dasatinib	Imatinib
Arm/Group Description	100 mg QD	600 mg QD
Measure Participants	0	0

6. Secondary Outcome

Title	Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs
Description	An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a patient or clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Time Frame	From 2 weeks prior to randomization through Month 36. At least every 4 weeks until all study-related toxicities resolve to baseline, stabilize, or are deemed irreversible.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Dasatinib	Imatinib
Arm/Group Description	100 mg QD	600 mg QD
Measure Participants	2	1
AEs	3	1
SAEs	0	0
AEs leading to Discontinuation	0	0
Deaths	0	0

7. Secondary Outcome

Title	Duration of CCyR and MMR
Description	Duration of CCyR computed for subjects with CCyR as best response; measured from time the criteria are first met for CCyR until date of progression or death. Duration of MMR computed for subjects with MMR as best response; measured from time the criteria are first met for MMR until date the MMR was first lost, disease progression or death.
Time Frame	Throughout the study

Outcome Measure Data

Analysis Population Description

This analysis was not done. This study was terminated due to insufficient enrollment.

Arm/Group Title	Dasatinib	Imatinib
Arm/Group Description	100 mg QD	600 mg QD
Measure Participants	0	0

8. Secondary Outcome

Title	Best MMR Rates
Description	MMR is defined as a 3-log reduction in BCR-ABL gene transcripts from a standardized baseline. Reductions in BCR-ABL transcripts on logarithmic scale are calculated based on the absolute values expressed as % of ratio of BCR-ABL gene transcripts to the control gene. In this study, ABL was used as the control gene.
Time Frame	throughout study

Outcome Measure Data

Analysis Population Description

This analysis was not done. This study was terminated due to insufficient enrollment.

Arm/Group Title	Dasatinib	Imatinib
Arm/Group Description	100 mg QD	600 mg QD
Measure Participants	0	0

Adverse Events

Arm/Group Title	Dasatinib		Imatinib
Arm/Group Description	100 mg once daily (QD)		600 mg QD
All Cause Mortality
	Dasatinib		Imatinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dasatinib		Imatinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Dasatinib		Imatinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		1/1 (100%)
Blood and lymphatic system disorders
Neutropenia	1/2 (50%)		0/1 (0%)
Investigations
Hypokalemia	0/2 (0%)		1/1 (100%)
Nervous system disorders
Headache	1/2 (50%)		0/1 (0%)
Skin and subcutaneous tissue disorders
Rash	1/2 (50%)		0/1 (0%)

Limitations/Caveats

Study was terminated early due to insufficient enrollment.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.