A Safety and Pharmacokinetics (PK) Study of Venetoclax in Participants With Non-Hodgkin's Lymphoma

Official Title

A Phase Ib/II, Open-Label Study Evaluating the Safety and Pharmacokinetics of GDC-0199 (ABT-199) in Combination With Rituximab (R) or Obinutuzumab (G) Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Patients With B-Cell Non-Hodgkin's Lymphoma (NHL) and DLBCL

Summary:

This is a multicentre, open-label, dose-finding study of venetoclax administered orally in combination with rituximab (R) or obinutuzumab (G) and standard doses of cyclophosphamide, doxorubicin, vincristine and oral prednisone (CHOP) in participants with Non-Hodgkin's Lymphoma (NHL). The study will consist of 2 stages: a dose-finding Phase Ib stage and a Phase II expansion stage. In the Phase I portion of the study, participants will be randomized to one of 2 treatment arms venetoclax in combination with R-CHOP (Arm A) and venetoclax in combination with G-CHOP (Arm B) and will explore the doses of venetoclax in combination with R-CHOP and G-CHOP. The maximum tolerated dose (MTD) of venetoclax in combination with R-CHOP and G-CHOP will be determined during the dose-finding stage. For the Phase II portion of the study, the venetoclax dose for venetoclax + R-CHOP is on a non-continuous dosing schedule as determined by the Phase Ib portion of the study based on safety and tolerability observed in participants treated in the dose escalation portion of the study.

Trial Description

Primary Outcome:

  • Safety: Percentage of Participants With Dose-Limiting Toxicities
  • Safety: MTD of Venetoclax
  • Percentage of Participants With Complete Response (CR) Defined by Positron Emission Tomography-Computed Tomography (PET-CT) Scan Using the Modified Lugano Classification
  • Percentage of Participants With CR Defined by PET-CT Scan in Double Positive Diffuse Large B-Cell Lymphoma (DP-DLBCL) Participants
Secondary Outcome:
  • Venetoclax Plasma PK: Area Under the Plasma Concentration-Time Curve (AUC)
  • Venetoclax Plasma PK: Time to Maximum Observed Plasma Concentration (Tmax)
  • Venetoclax Plasma PK: Maximum Observed Plasma Concentration (Cmax)
  • Venetoclax Plasma PK: Minimum Plasma Concentration (Cmin) within the Dosing Interval
  • Prednisone Plasma PK: AUC
  • Prednisone Plasma PK: Tmax
  • Prednisone Plasma PK: Cmax
  • Prednisone Plasma PK: Cmin within the Dosing Interval
  • Rituximab PK: Cmax
  • Rituximab PK: Cmin within the Dosing Interval
  • Obinutuzumab PK: Cmax
  • Obinutuzumab PK: Cmin within the Dosing Interval
  • Cyclophosphamide PK: Cmax
  • Cyclophosphamide PK: Cmin within the Dosing Interval
  • Doxorubicin PK: Cmax
  • Doxorubicin PK: Cmin within the Dosing Interval
  • Vincristine PK: Cmax
  • Vincristine PK: Cmin within the Dosing Interval
  • Percentage of Participants With Objective Response Defined as Partial or Complete Response Using the Modified Lugano Classification
  • Duration of Response Using the Modified Lugano Classification
  • Progression-Free Survival Using the Modified Lugano Classification
  • Percentage of Participants who are Alive and Without Disease Progression at Month 12
  • Overall Survival (OS)
  • Percentage of Participants With CR Defined by Computed Tomography (CT) Scan Using the Modified Lugano Classification
  • Safety: Percentage of Participants With Adverse Events
  • Safety: Percentage of Participants Maintaining Relative Dose Intensity of CHOP Chemotherapy
  • Venetoclax Metabolite Plasma PK: AUC
  • Venetoclax Metabolite Plasma PK: Tmax
  • Venetoclax Metabolite Plasma PK: Cmax
  • Venetoclax Metabolite Plasma PK: Cmin
  • Relative Dose Intensity of CHOP Chemotherapy

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

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