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

Sponsor

AbbVie (prior sponsor, Abbott) (Industry)

Overall Status

Completed

CT.gov ID

NCT00868413

Collaborator

Genentech, Inc. (Industry)

Enrollment

Locations

Arms

Duration (Months)

5.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia	Drug: ABT-263 Drug: FCR Drug: BR	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

32 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Nov 1, 2009

Actual Primary Completion Date :

May 1, 2013

Actual Study Completion Date :

May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: A FCR+ABT-263	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. Drug: 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 Other Names: fludarabine, cyclophosphamide, rituximab
Active Comparator: B BR+ABT-263	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. Drug: 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 Other Names: bendamustine, rituximab

Arm

Intervention/Treatment

Active Comparator: A

FCR+ABT-263

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.

Drug: 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

Other Names:

fludarabine, cyclophosphamide, rituximab

Active Comparator: B

BR+ABT-263

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.

Drug: 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

Other Names:

bendamustine, rituximab

Outcome Measures

Primary Outcome Measures

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

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. [Every 2 months]
Tumor assessments

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site Reference ID/Investigator# 17841	La Jolla	California	United States	92093
2	Site Reference ID/Investigator# 25899	Stanford	California	United States	94305-5821
3	Site Reference ID/Investigator# 21622	Baltimore	Maryland	United States	21231-1000
4	Site Reference ID/Investigator# 21621	Columbus	Ohio	United States	43210
5	Site Reference ID/Investigator# 39613	Philadelphia	Pennsylvania	United States	19111
6	Site Reference ID/Investigator# 17943	Houston	Texas	United States	77030-4009