Clinical trial NCT00481091: A Study of ABT-263 in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia
Official title: A Phase 1/2a Study Evaluating the Safety, Pharmacokinetics, and Efficacy of ABT-263 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Chronic Lymphocytic Leukemia
Keywords: Chronic Lymphocytic Leukemia (CLL)
Navitoclax
ABT-263
Cancer
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Genentech, Inc.
First posted: 2007-06-01
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* Relapsed or refractory CLL and require treatment in opinion of investigator.
* Eastern Cooperative Oncology Group (ECOG) \<= 1.
* Adequate bone marrow independent of growth factor support, renal and hepatic function per defined laboratory criteria.

Exclusion Criteria:

* History or is clinically suspicious for cancer-related Central Nervous System disease.
* Receipt of allogenic or autologous stem cell transplant.
* Recent history (within 1 year of first dose) of underlying, predisposing condition of bleeding or currently exhibits signs of bleeding.
* Active peptic ulcer disease or other potentially hemorrhagic esophagitis/gastritis.
* Active immune thrombocytopenic purpura or history of being refractory to platelet transfusions (within 1 year of first dose).

Primary outcomes:
measure: Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to Adverse Events (AEs)
timeFrame: From first dose of study drug to 30 days post-last dose. Participants enrolled in the 14/21-day cycle received a mean of 21.7 treatment cycles; participants enrolled in the 21/21-day cycle received a mean of 19.4 treatment cycles.
measure: Phase 1: Number of Participants With DLTs in the Dose Escalation Phase
timeFrame: Cycle 1 (Up to 21 days) plus 7 days
measure: Phase 1: Maximum Tolerated Dose (MTD) in the Dose Escalation Phase
timeFrame: Cycle 1 (Up to 21 days) plus 7 days
measure: Phase 1: Recommended Phase 2 Dose (RPTD) Determined in the Dose Escalation Phase
timeFrame: Cycle 1 (Up to 21 days) plus 7 days
measure: Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Navitoclax
timeFrame: Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
measure: Phase 1: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
measure: Phase 1: Area Under the Plasma Concentration-Time Curve From Time 0 to Hour 8 (AUC8)
timeFrame: Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
measure: Phase 1: Area Under the Plasma Concentration-Time Curve From Time 0 to Hour 24 (AUC24)
timeFrame: Cycle 1 Day 1: pre-dose, 2, 4, 6, 8, and 24 hours post-dose; Cycle 1 Days 14: pre-dose, 2, 4, 6, 8
measure: Phase 1: Cmax/Dose
timeFrame: Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
measure: Phase 1: AUC8/Dose
timeFrame: Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
measure: Phase 1: AUC24/Dose
timeFrame: Cycle 1 Day 1: pre-dose, 2, 4, 6, 8, and 24 hours post-dose; Cycle 1 Days 14: pre-dose, 2, 4, 6, 8
measure: Phase 1: Terminal Phase Elimination Rate Constant (β) for Navitoclax
timeFrame: Cycle 1 Day 1: pre-dose, 2, 4, 6, 8 hours post-dose
measure: Phase 1: Terminal Phase Elimination Half-life (t1/2) of Navitoclax
timeFrame: Cycle 1 Day 1: pre-dose, 2, 4, 6, 8 hours post-dose
measure: Phase 2: Number of Participants With TEAEs, SAEs, and Discontinuations Due to AEs
timeFrame: From first dose of study drug to 30 days post-last dose. Participants enrolled in Phase 2 received a mean of 15.6 treatment cycles.
measure: Phase 2: Dose-Normalized Plasma Concentrations After Navitoclax Once Daily Dosing
timeFrame: Cycle 1 Day 1: 4-8 h postdose; Cycle 1 Day 15: predose; Cycle 3 Day 1: predose, 4-8 h postdose; Cycle 5 Day 1: predose, 4-8 h postdose; Cycle 7 Day 1: predose, 4-8 h postdose; Cycle 9 Day 1: predose, 4-8 h postdose
Secondary outcomes:
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Moores Cancer Center at UC San Diego /ID# 5566
state: California
city: Boston
country: United States
facility: Dana-Farber Cancer Institute /ID# 5547
state: Massachusetts
city: Omaha
country: United States
facility: University of Nebraska Medical Center /ID# 12261
state: Nebraska
city: New Hyde Park
country: United States
facility: North Shore University Hospital /ID# 12267
state: New York
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center /ID# 5575
state: Texas
city: Tacoma
country: United States
facility: Northwest Medical Specialties - Tacoma /ID# 26428
state: Washington
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Ctr /ID# 6583
state: Victoria
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital /ID# 5576
state: Victoria
city: Köln
country: Germany
facility: Universitaetsklinikum Koeln /ID# 5924
state: Nordrhein-Westfalen
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary /ID# 15081
state: England
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References:
citation: Roberts AW, Seymour JF, Brown JR, Wierda WG, Kipps TJ, Khaw SL, Carney DA, He SZ, Huang DC, Xiong H, Cui Y, Busman TA, McKeegan EM, Krivoshik AP, Enschede SH, Humerickhouse R. Substantial susceptibility of chronic lymphocytic leukemia to BCL2 inhibition: results of a phase I study of navitoclax in patients with relapsed or refractory disease. J Clin Oncol. 2012 Feb 10;30(5):488-96. doi: 10.1200/JCO.2011.34.7898. Epub 2011 Dec 19.