A Study of Combination Therapy With Venetoclax, Daratumumab and Dexamethasone (With and Without Bortezomib) in Subjects With Relapsed or Refractory Multiple Myeloma

Official Title

A Phase 1/2, Multicentre, Dose-Escalation and Expansion Study of Combination Therapy With Venetoclax, Daratumumab and Dexamethasone (With and Without Bortezomib) in Subjects With Relapsed or Refractory Multiple Myeloma

Summary:

This is a study of venetoclax, daratumumab, and dexamethasone with and without bortezomib combination therapy to evaluate safety, tolerability, and efficacy of these combinations in participants with relapsed or refractory multiple myeloma. The study will consist of 2 distinct parts: Part 1 includes participants with t(11;14) positive relapsed/refractory (R/R) multiple myeloma who will receive venetoclax in combination with daratumumab and dexamethasone (VenDd); Part 2 includes participants with R/R multiple myeloma who will receive venetoclax in combination with daratumumab, bortezomib, and dexamethasone (VenDVd). Each Part will be initiated with a dose-escalation phase in which increasing doses of venetoclax will be given with fixed doses of daratumumab and dexamethasone (Part 1a) or with fixed doses of daratumumab, bortezomib, and dexamethasone (Part 2a). Each dose escalation phase will be followed by a single-arm, open-label expansion phase.

Trial Description

Primary Outcome:

• Part 1: Objective Response Rate (ORR)
• Part 1: Number of Participants with Dose Limiting Toxicities (DLT)
• Part 2: Number of Participants with Dose Limiting Toxicities (DLT)
• Part 2: Complete Response (CR)
• Very Good Partial Response or Better Response Rate (VGPR)

• ORR (Part 2b VenDVd Expansion)
• Trough Concentration (Ctrough) of Daratumumab
• Cmax of Daratumumab
• Time to Progression (TTP)
• Duration of Response (DOR)
• Progression-Free Survival (PFS)
• Cmax of Venetoclax
• AUC0-24 of Venetoclax
• Tmax of Venetoclax
• Minimal Residual Disease (MRD)

View this trial on ClinicalTrials.gov