Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma (MM)

NCT02899052 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: M15-5382019-004340-30
• Study Type: interventional
• Target: 120
• Locations: 5 countries
• Sites: 32

Brief Summary

A Phase 2, open-label, dose escalation study to evaluate the safety and efficacy of venetoclax in combination with carfilzomib-dexamethasone (Kd) in participants with relapsed or refractory MM and have received 1 to 3 prior lines of therapy. Part 4 of this study is currently enrolling.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Refractory myeloma; Relapsed myeloma; Relapsed or Refractory

Outcome Measures

Primary Outcomes (4)

• Number of Participants with Adverse Events

  An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

  First dose of study drug through at least 30 days after end of treatment (approximately 2 years)

• Very Good Partial Response (VGPR) or Better Response Rate of VenKd in Participants with Relapsed or Refractory Multiple Myeloma (RRMM) as well as Those with t(11;14)-positive RRMM

  VGPR or better response rate is defined as the percentage of participants with documented VGPR or better based on IMWG criteria.

  First dose of study drug through at least 30 days after end of treatment (approximately 2 years)

• Objective Response Rate (ORR) of VenKd in Participants with Relapsed or Refractory Multiple Myeloma (RRMM) as well as Those with t(11;14)-positive RRMM

  ORR is defined as the percentage of participants with a documented PR or better based on IMWG criteria.

  First dose of study drug through at least 30 days after end of treatment (approximately 2 years)

• Complete Response (CR) or Better Rate of VenKd in Participants with Relapsed or Refractory Multiple Myeloma (RRMM) as well as Those with t(11;14)-positive RRMM

  Complete response or better rate is defined as the percentage of participants with documented CR or better based on IMWG criteria.

  First dose of study drug through at least 30 days after end of treatment (approximately 2 years)

Secondary Outcomes (16)

• Very Good Partial Response (VGPR) or Better Response Rate in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression

  Up to approximately 17 months

• Progression-free survival (PFS) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression

  Up to approximately 17 months

• Minimal residual disease (MRD)

  Up to 2 years (Screening, Cycle 3 Day 1, and Confirmation of Stringent Complete Response [sCR]/Complete Response [CR])

• Duration of Overall Response (DOR) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression

  Up to approximately 17 months

• Time to progression (TTP) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression

  Up to approximately 17 months

Study Arms (1)

Venetoclax + Carfilzomib + Dexamethasone

EXPERIMENTAL

Part 1: Evaluate the safety and pharmacokinetic profiles while providing information to determine the appropriate doses of venetoclax and carfilzomib (VenKd) to be used in the VenKd combination in approximately 18 participants. The dose levels are Venetoclax 400 mg or 800 mg; Carfilzomib 20/27 mg/m2, 20/70 mg/m2, and/or 20/56 mg/m2; Dexamethasone 40 mg Part 2: Further evaluate the safety and efficacy profile of the VenKd combination selected after completion of Part 1 in approximately 22 additional participants. Participants may discontinue Kd but may continue receiving venetoclax once daily (QD) as monotherapy. Part 3: Further evaluation of the efficacy of the VenKd combination after completion of Part 1 and Part 2 in 7 additional participants. Part 4, An additional 65 participants t(11;14) positive will receive varying doses of the VenKd combination or carfilzomib and dexamethasone

Drug: Carfilzomib; Drug: Venetoclax; Drug: Dexamethasone

Interventions

Carfilzomib DRUG

Carfilzomib lyophilized administered intravenously as a 10 to 30 minute infusion in Cycles 1 and beyond within 30 minutes to 4 hours after dexamethasone dosing. Dose level 1 (K1) Cycle 1: 20 mg/m2 on Days 1 and 2, 27 mg/m2 on Days 8, 9, 15, and 16; Cycles 2 - 12: 27 mg/m2 on Days 1, 2, 8, 9, 15, and 16; Cycles 13 - 18: 27 mg/m2 on Days 1, 2, 15, and 16; Cycles 19 and beyond, for participants that have not previously transitioned to monotherapy: 27 mg/m2 on Days 1, 2, 15, and 16. Dose Level K2: Cycle 1: 20 mg/m2 on Day 1; 70 mg/m2 on Days 8 and 15 Cycles 2 - onward: 70 mg/m2 on Days 1, 8, and 15. Dose Level K3: Cycle 1: 20 mg/m2 on Days 1 and 2; 56 mg/m2 on Days 8, 9, 15, and 16. Cycles 2 - onward: 56 mg/m2 on Days 1, 2, 8, 9, 15, and 16.

Also known as: Kyprolis

Venetoclax + Carfilzomib + Dexamethasone

Venetoclax DRUG

Venetoclax tablet administered orally once daily during Cycles 1 - onward. Venetoclax dose level 1 (Ven1) 400 mg once daily, Ven2 800 mg once daily.

Also known as: Venclexta, ABT-199

Venetoclax + Carfilzomib + Dexamethasone

Dexamethasone DRUG

Dexamethasone tablet administered orally during Cycles 1 - onward. Dexamethasone dose level 1 (Dex1) 40 mg once weekly, Dex2 40 mg once weekly, Dex3 20 mg twice weekly.

Venetoclax + Carfilzomib + Dexamethasone

Eligibility Criteria

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

You may qualify if:

• Eastern Collaborative Oncology Group (ECOG) performance score of less than or equal to 2.
• Documented relapsed or progressive Multiple Myeloma (MM) on or after any regimen or is refractory to the most recent line of therapy.
• Positive for translocation t(11;14) as determined by an analytically validated Fluorescent In Situ Hybridization (FISH) assay per central laboratory testing.
• Received prior treatment with at least 1 prior line of therapy for MM.
• Measurable disease on Screening per International Myeloma Working Group (IMWG) criteria.
• Meets absolute neutrophil count, platelet count, hemoglobin, liver and kidney function laboratory values within 2 weeks prior to first dose of study drug.

You may not qualify if:

• Has a pre-existing condition that is contraindicated including.
• Non-secretory or oligo-secretory MM
• Active plasma cell leukemia.
• Waldenström's macroglobulinemia.
• Primary amyloidosis.
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
• Active hepatitis B or C infection based on screening blood testing.
• Known active Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
• Significant cardiovascular disease.
• Major surgery within 4 weeks prior to first dose.
• Acute infections requiring antibiotic, antifungal or antiviral therapy within14 days prior to first dose.
• Peripheral neuropathy ≥ Grade 3 or ≥ Grade 2 with pain within 2 weeks prior to first dose.
• Uncontrolled diabetes or uncontrolled hypertension within 14 days prior to first dose.
• Any other medical condition that, in the opinion of the Investigator, would adversely affect the participant's participation in the study.

Sponsors & Collaborators

• AbbVie: lead
• Genentech, Inc; Onyx Therapeutics, Inc.: collaborator

Study Sites (32)

University of Alabama at Birmingham - Main /ID# 151405

Birmingham, Alabama, 35233, United States

Location

University of Arkansas for Medical Sciences /ID# 151399

Little Rock, Arkansas, 72205, United States

Location

Memorial Healthcare System /ID# 224862

Hollywood, Florida, 33021-3513, United States

Location

Winship Cancer Institute of Emory University /ID# 161710

Atlanta, Georgia, 30322, United States

Location

The University of Chicago Medical Center /ID# 151395

Chicago, Illinois, 60637-1443, United States

Location

Indiana Blood & Marrow Transpl /ID# 218862

Indianapolis, Indiana, 46237, United States

Location

Duplicate_University of Kentucky Chandler Medical Center /ID# 151407

Lexington, Kentucky, 40536, United States

Location

Central Maine Medical Center /ID# 218856

Lewiston, Maine, 04240, United States

Location

Duplicate_University of Maryland School of Medicine /ID# 159721

Baltimore, Maryland, 21201-1544, United States

Location

Oncology Hematology Associates (OHA) - Springfield /ID# 218855

Springfield, Missouri, 65807-5287, United States

Location

Washington University-School of Medicine /ID# 222651

St Louis, Missouri, 63110, United States

Location

Duke Cancer Center /ID# 162062

Durham, North Carolina, 27710-3000, United States

Location

University of Pennsylvania /ID# 151768

Philadelphia, Pennsylvania, 19104-5502, United States

Location

University of Texas Southwestern Medical Center /ID# 218336

Dallas, Texas, 75390-7208, United States

Location

Baylor Scott & White Medical Center- Temple /ID# 218252

Temple, Texas, 76508-0001, United States

Location

University of Utah /ID# 151397

Salt Lake City, Utah, 84112-5500, United States

Location

Duplicate_VA Puget Sound Healthcare Syst /ID# 155369

Seattle, Washington, 98108, United States

Location

Aurora Health Care, Aurora Cancer Center /ID# 209612

Wauwatosa, Wisconsin, 53226-3436, United States

Location

Border Medical Oncology Research Unit Albury Wodonga Regiona /ID# 222200

East Albury, New South Wales, 2640, Australia

Location

Calvary Mater Newcastle /ID# 218739

Waratah, New South Wales, 2298, Australia

Location

Flinders Medical Centre /ID# 221345

Bedford Park, South Australia, 5042, Australia

Location

Royal Hobart Hospital /ID# 217546

Hobart, Tasmania, 7000, Australia

Location

Debreceni Egyetem-Klinikai Kozpont /ID# 217624

Debrecen, Hajdú-Bihar, 4032, Hungary

Location

Semmelweis Egyetem /ID# 217626

Budapest, 1085, Hungary

Location

Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet /ID# 217625

Budapest, 1097, Hungary

Location

Szegedi Tudományegyetem /ID# 219172

Szeged, 6720, Hungary

Location

Auxilio Mutuo Cancer Center /ID# 157853

San Juan, 00918, Puerto Rico

Location

VA Caribbean Healthcare System /ID# 157854

San Juan, 00921-3201, Puerto Rico

Location

Hospital Universitario Germans Trias i Pujol /ID# 218006

Badalona, Barcelona, 08916, Spain

Location

Hospital Clinic de Barcelona /ID# 218007

Barcelona, 08036, Spain

Location

Hospital General Universitario Gregorio Maranon /ID# 218005

Madrid, 28007, Spain

Location

Hospital Universitario Ramon y Cajal /ID# 220925

Madrid, 28034, Spain

Location

Related Publications (2)

• Badawi MA, Engelhardt B, Dobkowska E, Deng R, Kaufman JL, Menon R, Salem AH. Exposure-response relationships of venetoclax in combination with carfilzomib and dexamethasone in relapsed/refractory t(11;14) multiple myeloma patients. Invest New Drugs. 2024 Dec;42(6):635-643. doi: 10.1007/s10637-024-01471-x. Epub 2024 Oct 10.

  PMID: 39388024 DERIVED

• Costa LJ, Davies FE, Monohan GP, Kovacsovics T, Burwick N, Jakubowiak A, Kaufman JL, Hong WJ, Dail M, Salem AH, Yang X, Masud AA, Munasinghe W, Ross JA, Bueno OF, Kumar SK, Stadtmauer EA. Phase 2 study of venetoclax plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma. Blood Adv. 2021 Oct 12;5(19):3748-3759. doi: 10.1182/bloodadvances.2020004146.

  PMID: 34470049 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell; Recurrence

Interventions

carfilzomib; venetoclax; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; 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

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: September 1, 2016
• First Posted: September 14, 2016
• Study Start: January 19, 2017
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: August 5, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• Access Criteria: To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/

Locations

HU (4); AU (4); PR (2); US (18); ES (4)