A Study of Venetoclax in Combination With Pomalidomide and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma

NCT ID: NCT03567616

Last Updated: 2021-06-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-18
• Study Completion Date: 2020-06-18

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Dose Escalation

Venetoclax (400 mg oral \[PO\], once daily \[QD\]) administered with pomalidomide (4 mg PO, QD) and dexamethasone (40 mg once weekly \[qw\]) in 28-day cycles until documented disease progression, documented unacceptable toxicity, withdrawal of consent, or the participant met other criteria for discontinuation per study protocol

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Tablet; oral

Pomalidomide

Intervention Type: DRUG

Capsule; oral

Dexamethasone

Intervention Type: DRUG

Administered orally; for participants over 75 years of age, dexamethasone could have been administered at a 20 mg dose \[qw\]

Part 2: Dose Expansion, t(11;14) positive

Participants positive for t(11;14) translocation were to receive the venetoclax dose determined to be safe in Part 1 as well as pomalidomide (4 mg oral \[PO\], once daily \[QD\]) and dexamethasone (40 mg once weekly \[qw\])

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Tablet; oral

Pomalidomide

Intervention Type: DRUG

Capsule; oral

Dexamethasone

Intervention Type: DRUG

Administered orally; for participants over 75 years of age, dexamethasone could have been administered at a 20 mg dose \[qw\]

Part 2: Dose Expansion, t(11;14) negative

Participants negative for t(11;14) translocation were to receive the venetoclax dose determined to be safe in Part 1 as well as pomalidomide (4 mg oral \[PO\], once daily \[QD\]) and dexamethasone (40 mg once weekly \[qw\])

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Tablet; oral

Pomalidomide

Intervention Type: DRUG

Capsule; oral

Dexamethasone

Intervention Type: DRUG

Administered orally; for participants over 75 years of age, dexamethasone could have been administered at a 20 mg dose \[qw\]

Interventions

Venetoclax

Tablet; oral

Intervention Type: DRUG

Pomalidomide

Capsule; oral

Intervention Type: DRUG

Dexamethasone

Administered orally; for participants over 75 years of age, dexamethasone could have been administered at a 20 mg dose \[qw\]

Intervention Type: DRUG

Other Intervention Names

ABT-199; GDC-0199; Venclexta; Pomalyst

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: collaborator

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

Locations

John B. Amos Cancer Center - C /ID# 202055

Columbus, Georgia, United States

University of Kansas Cancer Center /ID# 201292

Fairway, Kansas, United States

Washington University-School of Medicine /ID# 201287

St Louis, Missouri, United States

Duke University Hospital /ID# 200805

Durham, North Carolina, United States

Ohio State Cancer Center /ID# 202443

Columbus, Ohio, United States

Hospital Universitario Germans Trias i Pujol /ID# 200959

Badalona, Barcelona, Spain

Hospital Universitario Vall d'Hebron /ID# 200967

Barcelona, , Spain

Hospital Clinico Universitario de Salamanca /ID# 200958

Salamanca, , Spain

Leicester Royal Infirmary /ID# 202238

Leicester, England, United Kingdom

Norfolk and Norwich Univ Hosp /ID# 202240

Norwich, Norfolk, United Kingdom

Univ Hospitals Birmingham NHS Foundation trust /ID# 203188

Birmingham, , United Kingdom

Countries

United States; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 34551886 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.rxabbvie.com/

This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.

Other Identifiers

2017-004232-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M16-085

Identifier Type: -

Identifier Source: org_study_id