Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 parenteral therapy
  • 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
Phase 2
Study Type
Interventional
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
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 /ID# 151405
Birmingham, Alabama 35233

University of Arkansas for Medical Sciences /ID# 151399
Little Rock, Arkansas 72205

Emory University Hospital /ID# 161710
Atlanta, Georgia 30322

University of Kentucky Chandler Medical Center /ID# 151407
Lexington, Kentucky 40536

University of Pennsylvania /ID# 151768
Philadelphia, Pennsylvania 19104-5502

University of Utah /ID# 151397
Salt Lake City, Utah 84112-5500

VA Puget Sound Healthcare Syst /ID# 155369
Seattle, Washington 98108

Auxilio Mutuo Cancer Center /ID# 157853
San Juan, Puerto Rico 00918

More Details

NCT ID
NCT02899052
Status
Recruiting
Sponsor
AbbVie

Study Contact

ABBVIE CALL CENTER
847.283.8955
abbvieclinicaltrials@abbvie.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.