Clinical trial NCT03567616: A Study of Venetoclax in Combination With Pomalidomide and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma
Official title: A Phase 2, Open-Label, Multicenter, Dose-Escalation and Expansion Study of Venetoclax in Combination With Pomalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Cancer
Multiple Myeloma (MM)
Relapsed or Refractory (R/R)
Venetoclax
Pomalidomide
Dexamethasone
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Celgene
First posted: 2018-06-26
Enrollment: 8
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: This was an open-label, multicenter study designed to evaluate the safety and preliminary efficacy of venetoclax combined with pomalidomide and dexamethasone in participants with relapsed or refractory (R/R) multiple myeloma (MM) who received at least 1 prior line of therapy with documented evidence of progression during or after the participant's last treatment regimen. The study was designed to consist of 2 parts: Part 1 (dose escalation) and Part 2 (dose expansion). For Part 2 the participants were to be divided into 2 cohorts, participants positive for t(11;14) translocation and participants negative for t(11;14) translocation.

Detailed description: Following communication of the results of the primary progression-free survival (PFS) analysis from the Phase 3 BELLINI study (Study M14-031; NCT02755597), the company-sponsored MM studies were placed on partial clinical hold (PCH) in March 2019 by the United States (US) Food and Drug Administration and enrollment was halted. The sponsor did not pursue release of the PCH for this study; therefore, enrollment was not re-opened. In accordance with the terms of the PCH, participants who were deriving clinical benefit were allowed to continue to receive treatment. One participant was still active in Part 1 of the study when the sponsor decided not to pursue release of the PCH (in January 2020) and, therefore, continued to receive treatment and have regular assessments until disease progression. The study was discontinued when the last participant completed study treatment. No participants were enrolled in Part 2 of the study.

Eligibility criteria: Inclusion Criteria:

* Relapsed or refractory (R/R) multiple myeloma (MM) with documented evidence of progression during or after the participant's last treatment regimen
* Measurable disease as described in the protocol
* Received at least 1 prior line of therapy as described in the protocol
* Must meet prior antimyeloma treatment parameters, as described in the protocol, and includes:
* Received at least 2 consecutive cycles of lenalidomide or a lenalidomide-containing regimen
* Refractory to lenalidomide
* Exposed to a proteasome inhibitor (PI) alone or in combination with another agent
* Had a response of partial response (PR) or better to prior therapy based on the investigator's determination of response as defined by International Myeloma Working Group (IMWG) criteria
* Has t(11;14) status as described in the protocol and meets the following criteria:
* For Part 1: MM participants independent of cytogenetic profile
* For Part 2, Arm A: participant must be t(11;14) positive
* For Part 2, Arm B: participant must be t(11;14) negative
* An Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Adequate kidney, liver and hematologic laboratory values

Exclusion Criteria:

* Previous treatment with venetoclax or other BCL-2 inhibitors, or previous treatment with pomalidomide
* Known sensitivity to any IMiDs
* Allogenic or syngeneic stem cell transplant within 6 months before the first dose of study drug or active ongoing graft versus host disease
* Autologous stem cell transplant within 12 weeks before the first dose of study drug
* Known meningeal involvement of MM

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: From first dose of study drug until 30 days following last dose of study drug (up to 70 weeks)
measure: Overall Response Rate (ORR)
timeFrame: Approximately 15 months
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Approximately 20 months
measure: Duration of Response (DOR)
timeFrame: Approximately 15 months
measure: Time-to-progression (TTP)
timeFrame: Approximately 15 months
Other outcomes:
Locations:
city: Columbus
country: United States
facility: John B. Amos Cancer Center - C /ID# 202055
state: Georgia
city: Fairway
country: United States
facility: University of Kansas Cancer Center /ID# 201292
state: Kansas
city: Saint Louis
country: United States
facility: Washington University-School of Medicine /ID# 201287
state: Missouri
city: Durham
country: United States
facility: Duke University Hospital /ID# 200805
state: North Carolina
city: Columbus
country: United States
facility: Ohio State Cancer Center /ID# 202443
state: Ohio
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol /ID# 200959
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron /ID# 200967
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca /ID# 200958
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary /ID# 202238
state: England
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich Univ Hosp /ID# 202240
state: Norfolk
city: Birmingham
country: United Kingdom
facility: Univ Hospitals Birmingham NHS Foundation trust /ID# 203188
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: Gasparetto C, Bowles KM, Abdallah AO, Morris L, Mander G, Coppola S, Wang J, Ross JA, Bueno OF, Arriola E, Mateos MV. A Phase II Study of Venetoclax in Combination With Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2021 Nov;21(11):775-784. doi: 10.1016/j.clml.2021.07.029. Epub 2021 Aug 1.