Randomized, Open Label Study of Dasatinib (100mg qd) vs. High-Dose Imatinib (600mg) in Patients With Chronic Phase CML Who Have Had Suboptimal Response After 3-18 Months of Therapy With Imatinib (400mg)
18 Years
N/A
Both
Chronic Myeloid Leukemia
Trial Information
Randomized, Open Label Study of Dasatinib (100mg qd) vs. High-Dose Imatinib (600mg) in Patients With Chronic Phase CML Who Have Had Suboptimal Response After 3-18 Months of Therapy With Imatinib (400mg)
Study Design: Prospective open-label, randomized two arms, multicenter study for the
patients with suboptimal response to standard Tx to evaluate efficacy & safety of dasatinib
(100mg qd) & imatinib (600mg daily) by CyR & MoR at 3, 6 & 12 months.
- Randomized 1:1
- Crossover to alternate be permitted after confirmed PD at 3M (AP, BC & loss of CHR or
MCyR) & absence of any response at 6M.
Duration of Study: Subjects will be treated for up to 12 months, unless disease progression
or unacceptable toxicity occurs, the subject withdraws, or the study is discontinued.
Duration of Study: Subjects will be treated for up to 12 months, unless disease progression
or unacceptable toxicity occurs, the subject withdraws, or the study is discontinued.
Number of Subjects: A total of 90 subjects will be randomized in 1:1 randomization ratio
Study Population: Subjects 18 years of age or older with CP Ph+ CML and who are imatinib
failures or ave achieved only a suboptimal response after 3 - 18 months (12 - 77 weeks) of
treatment with 400 mg/day of imatinib monotherapy.
Test Product, Dose and Mode of Administration, Duration of Treatment:
Subjects in the dasatinib arm will begin treatment with dasatinib at an oral dose of 100 mg
QD. One dose reduction to 70 mg due to toxicity will be allowed. One dose escalation to 140
mg is allowed under specified circumstances.
Reference Therapy, Dose and Mode of Administration, Duration of Treatment:
Subjects in the imatinib arm will begin treatment with imatinib at an oral dose of 600 mg QD
Doses of imatinib can be escalated to 800 mg for patients with inadequate response at 3
months and dose reduction of imatinib is not permitted for any cases of patients.
Criteria for Evaluation:
Efficacy:
- Primary Endpoint: CCyR rate at 6 months after randomization.
- Secondary Endpoints:
- MMR rates at 3, 6, and 12 months
- CCyR rates at 3, 6 and 12 months
- CHR rates at 3, 6and 12 months
- Time to-, and duration of-, MMR and CCyR
- Progression free survival (PFS)
Safety:
Adverse experiences associated with dasatinib or imatinib treatment will be reported for all
treated subjects. Adverse events will be assessed continuously and graded according to the
NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.
Inclusion Criteria:
1. Signed written informed consent, at least 18 years old
2. Adequate hepatic renal function
3. Dasatinib naïve patients
4. Patients with cytogenetically and/or molecularly confirmed Philadelphia chromosome or
BCR-ABL positive CP-CML who have been treated with standard dose of imatinib.
5. ECOG status: 0-2
6. And one of following criteria for imatinib suboptimal response 1)CP-CML patients who
have failed to achieve a CHR at 3 months or MCyR at 6 months of therapy with imatinib
400mg daily. 2)CP-CML patients who have failed to achieve a CCyR at 12 months with
imatinib 400mg daily 3)CP-CML patients who have failed to achieve a MMoR (less than 3
log reduction) at 18 months with imatinib 400mg daily 4)CP-CML patients who have lost
molecular response by an increase of BCR-ABL more than 10 times regardless treatment
duration.
Exclusion Criteria:
1. Concurrent malignancy
2. Patients who have received SCT
3. Allergy or hypersensitivity reaction to the study drugs
4. Female who are pregnant or breast feeding.
5. T315I mutation
6. History of significant bleeding disorder
7. Women of child bearing potential
8. Uncontrolled or significant CVS disease: IHD. CHF
9. Prior imatinib>400mg, imatinib>18 months
10. Intolerance to imatinib 400mg
Type of Study:
Expanded Access
Study Design:
N/A
Principal Investigator
Jooseop Chung, MD. PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Pusan National University Hospital, Korea
Authority:
Korea: Food and Drug Administration
Study ID:
CA180-257
NCT ID:
NCT00854841
Start Date:
Completion Date:
Related Keywords:
- Chronic Myeloid Leukemia
- CML
- suboptimal response
- dasatinib
- imatinib
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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