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

NCT00918450 | Withdrawn Phase 2

• 1 other identifier: M10-738
• Study Type: interventional
• Target: 150
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

B-cell Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• 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

Study Arms (1)

1

EXPERIMENTAL

Drug: ABT-263

Interventions

ABT-263 DRUG

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

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>= 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Abbott: lead
• Genentech, Inc.: collaborator

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

navitoclax

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 22, 2009
• First Posted: June 11, 2009
• Study Start: March 1, 2010
• Primary Completion: December 1, 2012
• Last Updated: February 26, 2010

Record last verified: 2010-02