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.



Eligible Ages
Over 18 Years
Eligible Genders
Accepts Healthy Volunteers

Inclusion Criteria

  • 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. - Received prior treatment with at least 1, but no more than 3, prior lines 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. - For Part 3, Cohort 7, participants must meet the above criteria and also be positive for translocation t(11;14) as determined by an analytically validated Fluorescent In Situ Hybridization (FISH) assay per central laboratory testing.

Exclusion Criteria

  • 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 - 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 subject's participation in the study. - History of other active malignancies, including myelodysplastic syndrome (MDS), within the past 3 years prior to study entry Other protocol defined inclusion/exclusion criteria could apply

Study Design

Phase 2
Study Type
Intervention Model
Single Group Assignment
Primary Purpose
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Venetoclax + Carfilzomib + Dexamethasone
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 9-18 subjects. 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 - 31 additional subjects. 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 60 additional subjects.
  • Drug: Carfilzomib
    Carfilzomib lyophilized administered intravenously as a 10 to 30 minute infusion in Cycles 1 - 18 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. Dose Level K2: Cycle 1: 20 mg/m2 on Day 1; 70 mg/m2 on Days 8 and 15 Cycles 2 - 18: 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 - 18: 56 mg/m2 on Days 1, 2, 8, 9, 15, and 16.
    Other names:
    • Kyprolis
  • Drug: Venetoclax
    Venetoclax tablet administered orally once daily during Cycles 1-18. Venetoclax dose level 1 (Ven1) 400 mg once daily, Ven2 800 mg once daily.
    Other names:
    • ABT-199
  • Drug: Dexamethasone
    Dexamethasone tablet administered orally during Cycles 1 - 18. Dexamethasone dose level 1 (Dex1) 40 mg once weekly, Dex2 40 mg once weekly, Dex3 20 mg twice weekly.

Recruiting Locations

University of Alabama at Birmingham - Main /ID# 151405
Birmingham, Alabama 35233

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