Study of Dasatinib and Bendamustine in Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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The purpose of this study is to determine the recommended dose for the combination of dasatinib and bendamustine in chronic lymphocytic leukemia (CLL).

Official Title
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Phase 1 Trial of Dasatinib and Bendamustine in Chronic Lymphocytic Leukemia

Conditions
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Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: Dasatinib
* Drug: Combination of Bendamustine + Dasatinib
* Drug: Dasatinib
* Drug: Combination of Bendamustine + Dasatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Cohort #1): Diagnosis of B-CLL by NCI criteria Require chemotherapy and have fully recovered from previous administered chemotherapy Subjects must have progressed, failed to achieve a meaningful response, or relapsed/intolerant to prior therapy. Failing at least one purine analogue regimen Subjects have received three or fewer prior treatment regimens ECOG status of 0 - 2 Inclusion Criteria (Cohort #2): If dose level + 3 is reached, the criteria is the same as outlined for Cohort #1, however the subjects should not have a history of prior chemotherapy (treatment naive) Exclusion Criteria: Unwilling or unable to use an acceptable method to avoid pregnancy Uncontrolled or significant cardiovascular disease, including prolonged QTc interval History of significant bleeding disorder, unrelated to CLL Prior concurrent malignancy Drugs that generally accepted to have the risk of causing Torsades de Pointes Autoimmune hemolytic anemia requiring therapy or transfusion support Autoimmune thrombocytopenia requiring steroid therapy or transfusion support Richter's Syndrome Transformation to prolymphocytic leukemia

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort #1<br> | Drug: Dasatinib<br>* One Week Initial Treatment for Cohort #1: Dasatinib - Tablets/Oral Solution, at assigned dose level, once daily (QD)<br>* Other names: Sprycel;Drug: Combination of Bendamustine + Dasatinib<br>* Dasatinib, Tablets/Oral Solution, Oral, 50 mg, then at 80 mg, at 80 mg, and at 100 mg, once daily (QD), at assigned ascending dose, for 28 day cycles for a maximum of six cycles Bendamustine, injection, IV injection, 50 mg/m²/Day 1 and Day 2, then at 50 mg/m², at 70 mg/m², at 70 mg/m², at assigned ascending dose, once daily 30 minute IV infusion Day 1 and Day 2 for a maximum of six cycles<br>* Other names: Treanda;|
| Experimental: Cohort #2<br> | Drug: Dasatinib<br>* One Week Initial Treatment for Cohort #2: Dasatinib - Tablets/Oral Solution, at 100 mg, once daily (QD)<br>* Other names: Sprycel;Drug: Combination of Bendamustine + Dasatinib<br>* Dasatinib, Tablets/Oral Solution, Oral, at 100 mg, once daily (QD), for 28 day cycles for maximum of six cycles Bendamustine, injection, IV injection, 100 mg/m²/Day 1 and Day 2, once daily 30 minute IV infusion Day 1 and Day 2 for maximum of six cycles<br>* Other names: Sprycel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the maximum tolerated dose (MTD) as assessed by measuring dose limiting toxicities (DLT) at each dosing level |  | From initial dose to the end of three cycles of treatment at each dosing level. Each cycle is 28 days, so approximately 91 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All response evaluable subjects Cohorts #1 and #2 are assessed for overall response rate(s): complete remission (CR); CR with incomplete marrow recovery (CRi); partial remission (PR); for progressive disease (PD) or stable disease (SD) |  | From initial dose to the end of six cycles of treatment. Each cycle is 28 days, so approximately 175 days | 
| The effects of treatment on various biological correlates will also be assayed |  | From initial dose to the end of six cycles of treatment. Each cycle is 28 days, so approximately 175 days |