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

NCT03567616 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: M16-0852017-004232-11
• Study Type: interventional
• Target: 8
• Locations: 3 countries
• Sites: 11

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.

Conditions

Multiple Myeloma

Keywords

Cancer; Multiple Myeloma (MM); Relapsed or Refractory (R/R); Venetoclax; Pomalidomide; Dexamethasone

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events

  An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either reasonable possibility or no reasonable possibility. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after the first dose of study drug. For more details on adverse events please see the Adverse Event section.

  From first dose of study drug until 30 days following last dose of study drug (up to 70 weeks)

• Overall Response Rate (ORR)

  ORR is defined as the percentage of participants experiencing a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) using the International Myeloma Working Group (IMWG) 2016 criteria for disease response and progression. CR= negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas, and \< 5% plasma cells in bone marrow; sCR= CR + normal serum free light chain (FLC) ratio and absence of clonal cells in bone marrow; VGPR= serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein level + urine M-protein level \< 100 mg per 24 hours; PR= ≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to \< 200 mg per 24 hours.

  Approximately 15 months

Secondary Outcomes (3)

• Progression-Free Survival (PFS)

  Approximately 20 months

• Duration of Response (DOR)

  Approximately 15 months

• Time-to-progression (TTP)

  Approximately 15 months

Study Arms (3)

Part 1: Dose Escalation

EXPERIMENTAL

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

Drug: Venetoclax; Drug: Pomalidomide; Drug: Dexamethasone

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

EXPERIMENTAL

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 \[qw\])

Drug: Venetoclax; Drug: Pomalidomide; Drug: Dexamethasone

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

EXPERIMENTAL

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 \[qw\])

Drug: Venetoclax; Drug: Pomalidomide; Drug: Dexamethasone

Interventions

Venetoclax DRUG

Tablet; oral

Also known as: ABT-199, GDC-0199, Venclexta

Part 1: Dose Escalation; Part 2: Dose Expansion, t(11;14) negative; Part 2: Dose Expansion, t(11;14) positive

Pomalidomide DRUG

Capsule; oral

Also known as: Pomalyst

Part 1: Dose Escalation; Part 2: Dose Expansion, t(11;14) negative; Part 2: Dose Expansion, t(11;14) positive

Dexamethasone DRUG

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

Part 1: Dose Escalation; Part 2: Dose Expansion, t(11;14) negative; Part 2: Dose Expansion, t(11;14) positive

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AbbVie: lead
• Celgene: collaborator

Study Sites (11)

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

Columbus, Georgia, 31904, United States

Location

University of Kansas Cancer Center /ID# 201292

Fairway, Kansas, 66205-2528, United States

Location

Washington University-School of Medicine /ID# 201287

St Louis, Missouri, 63110, United States

Location

Duke University Hospital /ID# 200805

Durham, North Carolina, 27710, United States

Location

Ohio State Cancer Center /ID# 202443

Columbus, Ohio, 43210, United States

Location

Hospital Universitario Germans Trias i Pujol /ID# 200959

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitario Vall d'Hebron /ID# 200967

Barcelona, 08035, Spain

Location

Hospital Clinico Universitario de Salamanca /ID# 200958

Salamanca, 37007, Spain

Location

Leicester Royal Infirmary /ID# 202238

Leicester, England, LE1 5WW, United Kingdom

Location

Norfolk and Norwich Univ Hosp /ID# 202240

Norwich, Norfolk, NR4 7UY, United Kingdom

Location

Univ Hospitals Birmingham NHS Foundation trust /ID# 203188

Birmingham, B15 2TG, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34551886 DERIVED

Related Links

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

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms; Recurrence

Interventions

venetoclax; pomalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• AbbVie Inc.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: June 12, 2018
• First Posted: June 26, 2018
• Study Start: October 18, 2018
• Primary Completion: June 18, 2020
• Study Completion: June 18, 2020
• Last Updated: June 30, 2021
• Results First Posted: June 30, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.

Locations

US (5); ES (3); GB (3)