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, or MRD progression, subjects may re-initiate ABT-199.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
49
Moores Cancer Center at UC San Diego /ID# 70398
La Jolla, California, United States
Northwestern University Feinberg School of Medicine /ID# 71593
Chicago, Illinois, United States
North Shore University Hospital /ID# 71813
New Hyde Park, New York, United States
Duke Cancer Center /ID# 71393
Durham, North Carolina, United States
Peter MacCallum Cancer Ctr /ID# 70394
Melbourne, Victoria, Australia
The Royal Melbourne Hospital /ID# 70393
Parkville, Victoria, Australia
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.
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.
Time frame: Continuous dosing at designated dose level up to Month 6. At end of combination treatment, ABT-199 monotherapy may continue up to 8 years following the date of the last subject enrolled. If disease progression occurs, subjects may re-initiate ABT-199.
Determination of peak concentration (Cmax) of ABT-199 and/or Rituximab.
Blood samples for analysis of ABT-199 and rituximab will be collected at designated time points.
Time frame: PK samples collected up to Month 6 for ABT-199 and Rituximab
Assess the exploratory efficacy of the combination ABT-199 and rituximab.
Tumor response or clinical disease progression (Objective Response Rate)
Time frame: Tumor Assessments will be performed at: Screening, Day 1 on Months 1, 3, 7, and then every 3 months thereafter up to 8 years following the date of the last subject first dose.
Determination of trough concentration (Ctrough) of ABT-199 and/or Rituximab
Blood samples for analysis of ABT-199 and rituximab will be collected at designated time points.
Time frame: PK samples collected up to Month 6 for ABT-199 and Rituximab
Determination of area under the concentration versus time curve (AUC) of ABT-199 and/or Rituximab
Blood samples for analysis of ABT-199 and rituximab will be collected at designated time points.
Time frame: PK samples collected up to Month 6 for ABT-199 and Rituximab
Assess the exploratory efficacy of the combination ABT-199 and rituximab
Tumor response or clinical disease progression for (Overall Survival)
Time frame: Tumor Assessments will be performed at: Screening, Day 1 on Months 1, 3, 7, and then every 3 months thereafter up to 8 years following the date of the last subject first dose.
Assess the exploratory efficacy of the combination ABT-199 and rituximab
Tumor response or clinical disease progression for (Progression Free Survival)
Time frame: Tumor Assessments will be performed at: Screening, Day 1 on Months 1, 3, 7, and then every 3 months thereafter up to 8 years following the date of the last subject first dose.
Assess the exploratory efficacy of the combination ABT-199 and rituximab
Tumor response or clinical disease progression for (Time to Tumor Progression)
Time frame: Tumor Assessments will be performed at: Screening, Day 1 on Months 1, 3, 7, and then every 3 months thereafter up to 8 years following the date of the last subject first dose.
Assess the exploratory efficacy of the combination ABT-199 and rituximab
Tumor response or clinical disease progression for (Duration Of Response)
Time frame: Tumor Assessments will be performed at: Screening, Day 1 on Months 1, 3, 7, and then every 3 months thereafter up to 8 years following the date of the last subject first dose.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.