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 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
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.
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.