The Randomized Study of Dasatinib and High-Dose Imatinib (600mg) in Suboptimal Responder

Study Purpose

Research Hypothesis: Treatment with dasatinib 100 mg QD is superior to imatinib 600 mg QD in terms of complete cytogenetic response (CCyR) in chronic phase (CP) Philadelphia chromosome-positive (Ph+) Chronic Myeloid Leukemia (CML) subjects who are imatinib failures or who have achieved only a suboptimal response after 3-18 months (12-77 weeks) of therapy with imatinib 400 mg. Primary Objective: The primary objective of this study is to compare the rate of CCyR of dasatinib (100mg QD) to high-dose imatinib (600 mg QD) therapy at 6 months after randomization in CP Ph+ CML subjects who are imatinib failures or who have achieved only a suboptimal response after 3

- 18 months of imatinib monotherapy at 400 mg/day.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	Unknown
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Expanded Access
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT00854841
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Pusan National University Hospital
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Jooseop Chung, MD. PhD
Principal Investigator Affiliation	Pusan National University Hospital, Korea
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Available
Countries
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Chronic Myeloid Leukemia

Additional Details

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.

Contact Information

This trial has no sites locations listed at this time. If you are interested in learning more, you can contact the trial's primary contact:

Jooseop Chung, MD. PhD

[email protected]

82-51-240-7242

For additional contact information, you can also visit the trial on clinicaltrials.gov.

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