Study of ABT-263 When Administered in Combination With Either Fludarabine/Cyclophosphamide/Rituximab or Bendamustine/Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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This is a Phase 1 study evaluating the safety of ABT-263 administered in combination with either FCR or BR in subjects with relapsed or refractory chronic lymphocytic leukemia.

Official Title
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A Phase 1 Study Evaluating the Safety of ABT-263 in Combination With Either Fludarabine/Cyclophosphamide/Rituximab (FCR) or Bendamustine/Rituximab (BR) in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia

Conditions
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Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: ABT-263
* Drug: FCR
* Drug: BR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have relapsed or refractory Chronic Lymphocytic Leukemia (CLL), received no more than 5 prior myelosuppressive/chemotherapy regimens and must be a candidate for treatment with either Fludarabine/Cyclophosphamide/Rituximab (FCR) or Bendamustine/Rituximab (BR); Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of </=1; Must have adequate bone marrow independent of growth factor support (with the exception of subjects with bone marrow heavily infiltrated with underlying disease [80% or more] who may use growth factor support to achieve Absolute Neutrophil Count (ANC) eligibility criteria), per local laboratory reference range at Screening as follows: ANC >/=1000/mcL, Platelets>/= 100,000/mm3 (entry platelet count must be independent of transfusion within 14 days of Screening),Hemoglobin >/= 9.0 g/dL. Exclusion Criteria: Subject has history or is clinically suspicious for cancer-related Central Nervous System disease; Has history of severe allergic or anaphylactic reactions to human, humanized, chimeric or murine monoclonal antibodies; Has undergone an allogeneic stem cell transplant; Exhibits evidence of other uncontrolled condition(s) including, but not limited to: uncontrolled systemic infection, diagnosis of fever and neutropenia within 1 week prior to study drug administration; Has underlying, predisposing condition of bleeding or currently exhibits signs of bleeding; Has a recent history of non-chemotherapy induced thrombocytopenic associated bleeding; Currently receiving or requires anticoagulation therapy; Has active immune thrombocytopenic purpura (ITP) or a history of being refractory to platelet transfusions (within 1 year prior to 1st dose of study drug); Has active peptic ulcer disease or other hemorrhagic esophagitis/gastritis.

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>FCR+ABT-263 | Drug: ABT-263<br>* ABT-263 is taken orally once daily for 3 days out of each 28 day cycle. This is a dose escalation study, therefore the dose of ABT-263 will change throughout the study.<br>Drug: FCR<br>* Rituximab will be given by intravenous infusion for 1 day out of each 28 day cycle; Fludarabine will be given by intravenous infusion for 3 days out of each 28 day cycle; and Cyclophosphamide will be given by intravenous infusion for 3 days out of each 28 day cycle<br>* Other names: fludarabine, cyclophosphamide, rituximab;|
| Active Comparator: B<br>BR+ABT-263 | Drug: ABT-263<br>* ABT-263 is taken orally once daily for 3 days out of each 28 day cycle. This is a dose escalation study, therefore the dose of ABT-263 will change throughout the study.<br>Drug: BR<br>* Rituximab will be given by intravenous infusion for 2 days out of each 28 day cycle and Bendamustine will be given by intravenous infusion for 2 days out of each 28 day cycle<br>* Other names: bendamustine, rituximab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the safety profile, characterize pharmacokinetics, and determine the MTD and recommended Phase 2 dose (RPTD) of ABT-263 when administered in combination with either FCR or BR in subjects with relapsed or refractory CLL. |  | Safety assessments = 1 wk, Pharmacokinetic (PK) Sampling = 1 wk for 1st 2 cycles, then, every other cycle starting Cycle 3 to Cycle 9, Determination of MTD & RPTD = Every 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate preliminary data regarding progression-free survival (PFS), tumor response rate and overall survival (OS) when ABT-263 is administered in combination with either FCR or BR. | Tumor assessments | Every 2 months |