Study Assessing the Safety and Efficacy of ABT-263 in Subjects With B-cell Chronic Lymphocytic Leukemia (CLL) Who Have Failed at Least One Prior Fludarabine-containing Regimen

Study Overview
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Brief Summary
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This is a Phase 2b, open-label, multicenter, global study assessing the safety and efficacy of ABT-263 in subjects with B-cell CLL who have failed at least one prior fludarabine-containing regimen.

Official Title
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A Phase 2b Monotherapy Study of ABT-263 in Subjects With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia

Conditions
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B-cell Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: ABT-263


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: >= 18 yrs of age, have B-cell CLL, failed at least 1 prior fludarabine-containing regimen. Refractory to 1 fludarabine-containing regimen is defined as failure to achieve at least PR to the last fludarabine-containing regimen received, or disease progression while receiving the last fludarabine-containing regimen, or disease progression in responders (i.e., achieved a PR or CR) within 6 mos of the last cycle of the last fludarabine-containing regimen received (e.g., fludarabine monotherapy, FR, or FC) or in responders (i.e., achieved a PR or CR ) within 24 mos of the last cycle of FCR. Intolerant to fludarabine is defined as discontinuation of therapy within 2 cycles due to side effects/toxicity from the last fludarabine-containing regimen. ECOG score of <=1. Adequate coagulation, renal, & hepatic function at Screening as follows: Serum creatinine <= 2.0 mg/dL or calculated creatinine clearance >= 50 mL/min; AST & ALT <= 3.0 x ULN; Bilirubin <= 1.5 x ULN. Gilbert's Syndrome may have a Bilirubin > 1.5 x ULN; aPTT, PT, not to exceed 1.2 x ULN. Adequate bone marrow (BM) independent of any growth factor support (with the exception of subjects with BM heavily infiltrated with underlying disease [80% or more] who may use growth factor support to achieve adequate BM) at Screening as follows: ANC >= 1000/µL; Platelets >= 75,000/mm3 (entry platelet count must be independent of transfusion within 14 days of Screening); Hemoglobin >= 9.0 g/dL. History of autologous BM transplant must be > 6 mos post transplant (prior to the 1st dose of study drug) & have adequate BM independent of any growth factor support (with the exception of subjects with BM that is heavily infiltrated with underlying disease [80% or more] who may use growth factor support to achieve adequate BM) at Screening as follows: ANC >= 1500/µL; Platelets >= 125,000/mm3; Hemoglobin >= 10.0 g/dL. Female subjects must be surgically sterile, postmenopausal (at least 1 year), or have negative results on a pregnancy test. All female subjects not surgically sterile or postmenopausal (at least 1 year) & non-vasectomized male subjects must practice birth control. Exclusion Criteria: History/clinically suspicious for cancer-related CNS disease. Undergone allogeneic stem cell transplant. Undergone autologous stem cell transplant w/i 6 mos prior to 1st dose. History/predisposing condition of bleeding or currently exhibits signs of bleeding. Recent history of non-chemotherapy induced thrombocytopenic associated bleeding w/i 6 mos prior to 1st dose. Active peptic ulcer disease or other hemorrhagic esophagitis/gastritis. Active immune thrombocytopenic purpura or history of being refractory to platelet transfusions w/i 1 yr prior to 1st dose. Currently receiving/requires anticoagulation therapy or any drugs or herbal supplements that affect platelet function, with the exception of low-dose anticoagulation medications used to maintain the patency of a central IV catheter. Significant history of cardiovascular disease, renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, or hepatic disease. Positive for HIV, Hepatitis B, or Hepatitis C. Previous or current malignancies w/i the last 3 yrs: except adequately treated in situ carcinoma of the cervix uteri; basal or squamous cell carcinoma; in situ carcinoma of the bladder; or previous malignancy confined and surgically resected with curative intent. Has Prolymphocytic leukemia or Richter's transformation to an aggressive B-cell malignancy. Exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to uncontrolled systemic infection or diagnosis of fever and neutropenia w/i 1 week prior to study drug. Prior exposure to ABT-263. Received antibody therapy w/i 30 days prior to 1st dose. Received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal, or any investigational therapy w/i 14 days prior to the 1st dose, or has not recovered to <Gr2 clinically significant AE(s) /toxicity(s) of the previous therapy. Received steroid therapy for anti-neoplastic intent, w/i 7 days prior to the 1st dose with the exception of inhaled steroids for asthma, topical steroids, or replacement/stress corticosteroids. Received aspirin w/i 7 days prior to the 1st dose. Consumed grapefruit or grapefruit products w/i 3 days prior to 1st dose. Females pregnant or breast-feeding.

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: 1<br> | Drug: ABT-263<br>* Continuous dosing until disease progression using one of the following formulations: 25 mg/mL oral solution OR 50 mg/mL oral solution OR 2.0 grams/bottle powder for oral solution of 25 mg/mL when mixed OR 2.0 grams/bottle powder for oral solution of 50 mg/mL when mixed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the safety of ABT-263 by evaluating study drug exposure, adverse events, serious adverse events, all deaths, as well as changes in laboratory determinations and vital sign parameters. |  | monthly (at a minimum) | 
| Assess the objective response rate (partial response [PR] and confirmed complete response [CR]) of B-cell CLL subjects treated with ABT-263. |  | Every 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the effects of ABT-263 on duration of overall response, PFS and overall survival in subjects with B-cell CLL. |  | Every 3 months | 
| Assess the effects of ABT-263 on time to response, 12-month survival rate, time to disease progression (TTP), and disease control rate in subjects with B-cell CLL . |  | Every 3 months | 
| Investigate the effects of ABT-263 on quality of life (FACT-Leu and EQ-5D), ECOG performance status, and biomarkers in subject with B-cell CLL. |  | Every 3 months |