A Study of ABT-263 in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia
Study Details
Study Description
Brief Summary
The Phase 1 portion of the study will evaluate the pharmacokinetic profile and safety of ABT-263 under two different dosing schedules with the objective of defining the dose limiting toxicity and maximum tolerated dose. The Phase 2a portion of the study will evaluate ABT-263 at the defined recommended Phase 2 dose to obtain additional safety information and a preliminary assessment of efficacy. The Extension Study portion will allow active subjects to continue to receive ABT-263 for up to 11 years after the last subject transitions with less frequent study evaluations.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Phase 1: Dose Escalation Portion Participants will receive escalating doses of ABT-263 to determine the recommended phase 2 dose (RPTD). Eligible participants can continue to receive ABT-263 for 11 years in the extension portion. |
Drug: ABT-263
Tablet; Oral
Other Names:
|
Experimental: Phase 2a: Dose Expansion Portion Participants will receive ABT-263 at the RPTD determined in Phase 1 portion. Eligible participants can continue to receive ABT-263 for 11 years in the extension portion. |
Drug: ABT-263
Tablet; Oral
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants with Adverse Events [Up to approximately 13 years]
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related.
- Number of Participants with Dose Limiting Toxicity (DLT) in the Dose Escalation Phase (Phase 1) [Cycle 1 (Up to 21 days)]
DLTs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0.
- Maximum Tolerated Dose (MTD) in the Dose Escalation Phase (Phase 1) [Cycle 1 (Up to 21 days)]
The MTD will be determined by using available clinical data during dose escalation in phase 1.
- Recommended Phase 2 Dose (RPTD) Determined in the Dose Escalation Phase (Phase 1) [Cycle 1 (Up to 21 days)]
The RPTD will be determined based on observed dose-limiting toxicities (DLTs) and/or determination of the maximum tolerated dose (MTD) in phase 1.
- Maximum Observed Plasma Concentration (Cmax) of Navitoclax (Phase 1) [Up to Day 14]
Cmax of navitoclax.
- Time to Maximum Observed Plasma Concentration (Tmax) of Navitoclax (Phase 1) [Up to Day 14]
Tmax of navitoclax.
- Terminal phase elimination rate constant (β) for Navitoclax (Phase 1) [Day 1]
Terminal phase elimination rate constant (β) for navitoclax.
- Terminal phase elimination half-life (t1/2) of Navitoclax (Phase 1) [Day 1]
Terminal phase elimination half-life (t1/2) of navitoclax.
- Area Under the Plasma Concentration-time Curve over time from 0 to 24 hours (AUC0-24) of Navitoclax (Phase 1) [Day 1]
AUC0-24 of navitoclax.
- Area Under the Plasma Concentration-time Curve over time from 0 to 8 hours (AUC0-8) of Navitoclax (Phase 1) [Day 14]
AUC0-8 of navitoclax.
- Progression-free Survival (PFS) (Extension Portion) [Up to approximately 13 years]
PFS defined as the time from the date the participant started study drug to the date the participant experiences an event of disease progression.
- Overall Survival (OS) (Extension Portion) [Up to approximately 13 years]
OS defined as the time from the date the participant started study drug to the date the participant's death.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Relapsed or refractory Chronic Lymphocytic Leukemia and require treatment in opinion of investigator.
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Eastern Cooperative Oncology Group (ECOG) <= 1.
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Adequate bone marrow independent of growth factor support, renal and hepatic function per defined laboratory criteria.
Exclusion Criteria:
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History or is clinically suspicious for cancer-related Central Nervous System disease.
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Receipt of allogenic or autologous stem cell transplant.
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Recent history (within 1 year of first dose) of underlying, predisposing condition of bleeding or currently exhibits signs of bleeding.
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Active peptic ulcer disease or other potentially hemorrhagic esophagitis/gastritis.
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Active immune thrombocytopenic purpura or history of being refractory to platelet transfusions (within 1 year of first dose).
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Moores Cancer Center at UC San Diego /ID# 5566 | La Jolla | California | United States | 92093 |
2 | Dana-Farber Cancer Institute /ID# 5547 | Boston | Massachusetts | United States | 02215 |
3 | University of Nebraska Medical Center /ID# 12261 | Omaha | Nebraska | United States | 68198 |
4 | North Shore University Hospital /ID# 12267 | New Hyde Park | New York | United States | 11040 |
5 | University of Texas MD Anderson Cancer Center /ID# 5575 | Houston | Texas | United States | 77030 |
6 | Northwest Medical Specialties - Tacoma /ID# 26428 | Tacoma | Washington | United States | 98405 |
7 | Peter MacCallum Cancer Ctr /ID# 6583 | Melbourne | Victoria | Australia | 3000 |
8 | The Royal Melbourne Hospital /ID# 5576 | Parkville | Victoria | Australia | 3050 |
9 | Universitaetsklinikum Koeln /ID# 5924 | Köln | Nordrhein-Westfalen | Germany | 50937 |
10 | Leicester Royal Infirmary /ID# 15081 | Leicester | England | United Kingdom | LE1 5WW |
Sponsors and Collaborators
- AbbVie
- Genentech, Inc.
Investigators
- Study Director: ABBVIE INC., AbbVie
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- M06-873
- 2007-002143-25