A Phase 1b Study Evaluating the Safety and Tolerability of ABT-199 in Combination With Rituximab in Subjects With Relapsed Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma
This is a Phase 1b, open-label, multicenter study evaluating the safety and tolerability of ABT-199 in combination with rituximab in up to 50 subjects with Relapsed Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma. The primary objectives of this study are to assess the safety profile, to determine the maximum tolerated dose and establish the Recommended Phase Two Dose of ABT-199 when administered in combination with rituximab. The dose escalation portion of the study will include approximately 30 subjects. Once the recommended phase two dose and schedule have been determined, up to 20 additional subjects will be enrolled in an expanded safety portion of the study. Subjects who meet criteria for CR, CRi, or MRD-negative PR during the study may discontinue ABT 199. If disease progression occurs, as defined by iwCLL NCI/WG criteria for tumor response, subjects may re-initiate ABT-199.
Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1b Study Evaluating the Safety and Tolerability of ABT-199 in Combination With Rituximab in Subjects With Relapsed Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma|
- Assess the safety profile, to determine the maximum tolerated dose and Recommended Phase Two Dose of ABT-199 when administered in combination with rituximab (R) in subjects with relapsed chronic lymphocytic leukemia and small lymphocytic lymphoma. [ Time Frame: Continuous dosing at designated dose level up to Month 6. At end of combination treatment, ABT-199 monotherapy may continue up to 4 years following the date of the last subject enrolled. If disease progression occurs, subjects may re-initiate ABT-199. ] [ Designated as safety issue: Yes ]Protocol-defined events, which are attributed as having a reasonable possibility of being related to the administration of ABT-199 and/or rituximab, or can not be attributed by the investigator to a clearly identifiable cause such as tumor progression, concurrent illness, underlying disease or concomitant medication, will be considered a dose limiting toxicity.
- Assess the exploratory efficacy of the combination ABT-199 and rituximab. [ Time Frame: Tumor Assessments will be performed at: Screening, Day 1 on Months 1, 3, 7, and then every 3 months thereafter. In addition, tumor assessment will be performed at least 2 months after Cr or CRi. ] [ Designated as safety issue: No ]Tumor response or clinical disease progression
- Determination of peak concentration (Cmax), trough concentration (Ctrough) and/or area under the concentration versus time curve (AUC) of ABT-199 and/or Rituximab. [ Time Frame: PK samples collected up to Month 6 for ABT-199 and Rituximab. Re-initiated subjects have PK samples collected on Day 1 of Weeks 1 and 3, Day 1 of Months 1 and 4. ] [ Designated as safety issue: No ]Blood samples for analysis of ABT-199 and rituximab will be collected at designated time points.
- Assess the exploratory pharmacodynamics and pharmacogenetics of the combination of ABT-199 and rituximab. [ Time Frame: MRD Assessments will be performed at following timepoints: At least 2 months after CR/CRi criteria for tumor response first met, every 12 weeks thereafter until MRD negativity is achieved, and as needed. ] [ Designated as safety issue: Yes ]Minimal residual disease (MRD) will be assessed in the peripheral blood and bone marrow (BM) either by flow cytometry or real-time PCR.
|Study Start Date:||August 2012|
|Estimated Study Completion Date:||May 2018|
|Estimated Primary Completion Date:||May 2018 (Final data collection date for primary outcome measure)|
Experimental: Arm 1
Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)
ABT-199 is taken continuously once daily. This is a dose escalation study, therefore the dose of ABT-199 will change throughout the study.
Other Name: venetoclaxDrug: Rituximab
Rituximab will be given by intravenous infusion on day 1 of Months 1, 2, 3, 4, 5, and 6.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01682616
|United States, California|
|Site Reference ID/Investigator# 70398|
|La Jolla, California, United States, 92093|
|United States, Illinois|
|Site Reference ID/Investigator# 71593|
|Chicago, Illinois, United States, 60611|
|United States, New York|
|Site Reference ID/Investigator# 71813|
|New Hyde Park, New York, United States, 11042|
|United States, North Carolina|
|Site Reference ID/Investigator# 71393|
|Durham, North Carolina, United States, 27710|
|Site Reference ID/Investigator# 70394|
|East Melbourne, Australia, 3002|
|Site Reference ID/Investigator# 70393|
|Parkville, Australia, 3050|
|Study Director:||Su Y Kim, MD||AbbVie|