Clinical Trials /

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

NCT02899052

Description:

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (MM)
  • Official Title: A Phase 2, Open-Label, Multi-Center Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: M15-538
  • NCT ID: NCT02899052

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
CarfilzomibKyprolisVenetoclax + Carfilzomib + Dexamethasone
VenetoclaxABT-199Venetoclax + Carfilzomib + Dexamethasone
DexamethasoneVenetoclax + Carfilzomib + Dexamethasone

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.

Trial Arms

NameTypeDescriptionInterventions
Venetoclax + Carfilzomib + DexamethasoneExperimentalPart 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.
  • Carfilzomib
  • Venetoclax
  • Dexamethasone

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse events
Time Frame:First dose of study drug through at least 30 days after end of treatment (approximately 2 years)
Safety Issue:
Description:ORR is defined as the percentage of participants with a documented PR or better based on IMWG criteria,

Secondary Outcome Measures

Measure:Very Good Partial Response (VGPR) or better response rate in participants with relapsed or refractory MM and in a subset of participants with high BCL-2 expression
Time Frame:Up to approximately 17 months
Safety Issue:
Description:VGPR or better response rate is defined as the proportion of participants with documented VGPR or better based on IMWG criteria.
Measure:Progression-free survival (PFS) in participants with relapsed or refractory MM and in a subset of participants with high BCL-2 expression
Time Frame:Up to approximately 17 months
Safety Issue:
Description:PFS is defined as the number of days from the date of the first dose of study drug to the date of the first documented progressive disease (PD) or death due to any cause, whichever occurs first.
Measure:Minimal residual disease (MRD)
Time Frame:Up to 2 years (Screening, Cycle 3 Day 1, and Confirmation of Stringent Complete Response [sCR]/Complete Response [CR])
Safety Issue:
Description:MRD in the bone marrow by next generation sequencing.
Measure:Area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) post-dose of venetoclax
Time Frame:Approximately 24 hours post-dose on Cycle 1 Days 1 and 15
Safety Issue:
Description:
Measure:Clearance (CL) of carfilzomib
Time Frame:Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Safety Issue:
Description:
Measure:Duration of overall response (DOR) in participants with relapsed or refractory MM and in a subset of participants with high BCL-2 expression
Time Frame:Up to approximately 17 months
Safety Issue:
Description:DOR is defined as the number of days from the participant's date of first documented response (PR or better) to the date of first documented PD or death due to MM, whichever occurs first.
Measure:Terminal phase elimination rate constant (β) of carfilzomib
Time Frame:Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Safety Issue:
Description:
Measure:AUC from 0 to infinity (AUC∞)of carfilzomib
Time Frame:Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Safety Issue:
Description:
Measure:Time to progression (TTP) in participants with relapsed or refractory MM and in a subset of participants with high BCL-2 expression
Time Frame:Up to approximately 17 months
Safety Issue:
Description:TTP is defined as the number of days from the date of the first dose of study drug to the date of first documented PD or death due to MM, whichever occurs first.
Measure:AUC from time 0 to the time of the last measurable concentration (AUCt) of carfilzomib
Time Frame:Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Safety Issue:
Description:
Measure:Objective response rate (ORR) in participants with relapsed or refractory MM and in a subset of participants with high B-cell lymphocyte-2 (BCL-2) expression
Time Frame:Up to approximately 17 months
Safety Issue:
Description:ORR is defined as the proportion of participants with documented partial response (PR) or better based on International Myeloma Working Group (IMWG) criteria.
Measure:Cmax of carfilzomib
Time Frame:Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Safety Issue:
Description:
Measure:Terminal elimination half-life (t1/2) of carfilzomib
Time Frame:Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Safety Issue:
Description:
Measure:Time to maximum plasma concentration (peak time, Tmax) of venetoclax
Time Frame:Approximately 24 hours post-dose on Cycle 1 Days 1 and 15
Safety Issue:
Description:
Measure:Maximum plasma concentration (Cmax) of venetoclax
Time Frame:Approximately 24 hours post-dose on Cycle 1 Days 1 and 15
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AbbVie

Trial Keywords

  • Multiple Myeloma
  • Refractory myeloma
  • Relapsed myeloma
  • Relapsed or Refractory

Last Updated

September 24, 2019