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

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00868413
• Other study ID #: M10-458
• Status: Completed
• Phase: Phase 1
• First received: March 20, 2009
• Last updated: June 5, 2013
• Start date: November 2009
• Est. completion date: May 2013

Study information

• Verified date: May 2013
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• ABT-263
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.
• FCR
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
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

Locations

Country	Name	City	State
United States	Site Reference ID/Investigator# 21622	Baltimore	Maryland
United States	Site Reference ID/Investigator# 21621	Columbus	Ohio
United States	Site Reference ID/Investigator# 17943	Houston	Texas
United States	Site Reference ID/Investigator# 17841	La Jolla	California
United States	Site Reference ID/Investigator# 39613	Philadelphia	Pennsylvania
United States	Site Reference ID/Investigator# 25899	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
AbbVie (prior sponsor, Abbott)	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	No