Clinical Trials /

Study of Early Relapsed, Lenalidomide-refractory Subjects Eligible for Carfilzomib Triplet

NCT04191616

Description:

A Study Evaluating Treatment of Multiple Myeloma with Carfilzomib in Combination with Pomalidomide and Dexamethasone

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Early Relapsed, Lenalidomide-refractory Subjects Eligible for Carfilzomib Triplet
  • Official Title: An Open-label, Phase 2 Study Treating Subjects With First or Second Relapse of Multiple Myeloma With Carfilzomib, Pomalidomide, and Dexamethasone (KPd)

Clinical Trial IDs

  • ORG STUDY ID: 20180117
  • SECONDARY ID: 2019-001169-34
  • NCT ID: NCT04191616

Conditions

  • Relapsed or Refractory Multiple Myeloma

Interventions

DrugSynonymsArms
CarfilzomibKyprolisCarfilzomib combined with pomalidomide and dexamethasone
DexamethasoneDecadron, Ozurdex, DexPak 6, 10, 13 Day, ReadySHarp, LoCort, MaxidexCarfilzomib combined with pomalidomide and dexamethasone
PomalidomidePomalystCarfilzomib combined with pomalidomide and dexamethasone

Purpose

A Study Evaluating Treatment of Multiple Myeloma with Carfilzomib in Combination with Pomalidomide and Dexamethasone

Detailed Description

      An Open-label, Phase 2 Study Treating Subjects with First or Second Relapse of Multiple
      Myeloma with Carfilzomib, Pomalidomide, and Dexamethasone (KPd)

      This trial is designed to estimate the efficacy of a carfilzomib-based triplet in first or
      second relapse of multiple myeloma for subjects refractory to lenalidomide and exposed to
      daratumumab The study is an open-label, phase 2 trial. Approximately 85 subjects will be
      enrolled in the study. Subjects may receive treatment until progression.

      Myeloma disease status will be monitored locally for response and progression per
      International Myeloma Working Group (IMWG) criteria (Kumar et al, 2016) every 28 ± 7 days
      from cycle 1 day 1 until confirmed progressive disease (PD), death, lost to follow-up, or
      withdrawal of full consent (whichever occurs first), regardless of cycle duration, dose
      delays or treatment discontinuation. Subjects with a suspected complete response (CR) or
      better will have a bone marrow for minimal residual disease (MRD) assessment at 12 and 24
      months (± 4 weeks) from start of treatment (unless a MRD assessment was performed within 4
      months before planned assessment).

      Subjects who end study drug(s) without confirmed PD are required to complete disease response
      assessments and report new anti-myeloma treatment every 28 ± 7 days until first subsequent
      anti-myeloma treatment, death, lost to follow-up, withdrawal of full consent, confirmed PD,
      or end of study, whichever occurs first. Subjects who discontinue treatment and either start
      new antimyeloma treatment or have PD will enter long-term follow-up every 12 weeks until
      death or end of study.

      Approximately 85 subjects will be enrolled in the study, with approximately one-third of
      subjects in first relapse and two-thirds in second relapse.

      This study will enroll adults ≥ 18 years of age with first or second relapse multiple
      myeloma.

      Eligible subjects will have relapsed multiple myeloma after receiving 1 or 2 prior lines of
      therapy.

      Subjects must be refractory to lenalidomide and completed at least 2 consecutive cycles of
      daratumumab.

      Subjects may not have received prior pomalidomide. Prior exposure to a proteasome inhibitor
      is allowed. Subjects previously exposed to carfilzomib must have responded with at least a
      partial response to carfilzomib, must not have discontinued carfilzomib due to toxicity, may
      not have relapsed while receiving or within 60 days of the last dose of carfilzomib, and must
      have at least a 6 month carfilzomib treatment-free interval since their last dose of
      carfilzomib.

      Subjects must have measurable disease per IMWG consensus criteria, Eastern Cooperative
      Oncology Group Performance Status (ECOG PS) of 0 to 2, and at least partial response (PR) to
      1 line of therapy.
    

Trial Arms

NameTypeDescriptionInterventions
Carfilzomib combined with pomalidomide and dexamethasoneExperimentalCarfilzomib, pomalidomide, and dexamethasone (KPd)
  • Carfilzomib
  • Dexamethasone
  • Pomalidomide

Eligibility Criteria

        Inclusion Criteria

          -  Subject has provided informed consent prior to initiation of any study specific
             activities or procedures.

          -  Male or female subjects age ≥ 18 years

          -  First or second relapse of multiple myeloma by International Myeloma Working Group
             (IMWG) criteria (subjects refractory to the most recent line of therapy, excluding
             carfilzomib, are eligible)

          -  Prior treatment with lenalidomide

          -  Prior treatment includes completion of at least 2 consecutive cycles of daratumumab

          -  Measurable disease with at least 1 of the following assessed within 28 days prior to
             enrollment:

               -  IgG multiple myeloma: serum monoclonal protein (M-protein) level ≥ 1.0 g/dL

               -  IgA, IgD, IgE multiple myeloma: serum M-protein level ≥ 0.5 g/dL

               -  urine M-protein ≥ 200 mg per 24 hours

               -  in subjects without measurable serum or urine M-protein, serum-free light chain
                  (SFLC) ≥ 100 mg/L (involved light chain) and an abnormal serum kappa lambda ratio

          -  Must have at least a partial response (PR) to at least 1 line of prior therapy

          -  Prior therapy with PI is allowed. Subjects receiving prior carfilzomib therapy must
             have achieved at least a PR, was not removed due to toxicity, did not relapse within
             60 days from discontinuation of carfilzomib, and must have at least a 6 month
             carfilzomib treatment-free interval from their last dose of carfilzomib

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2

        Exclusion Criteria

          -  Primary refractory multiple myeloma

          -  Waldenström macroglobulinemia

          -  Multiple myeloma of IgM subtype

          -  POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and
             skin changes)

          -  Plasma cell leukemia ( greater than 2.0 × 109/L circulating plasma cells by
             differential). If automated differential shows ≥ 20% of other cells, obtain manual
             differential to identify other cells.

          -  Primary amyloidosis (patients with multiple myeloma with asymptomatic deposition of
             amyloid plaques found on biopsy would be eligible if all other criteria are met)

          -  Previous diagnosis of amyloidosis associated with myeloma

          -  Myelodysplastic syndrome

          -  Toxicity requiring discontinuation of lenalidomide therapy

          -  Prior treatment with pomalidomide
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with best minimal residual disease negative complete response (MRD[-]CR)
Time Frame:12 Months
Safety Issue:
Description:Best MRD[-]CR response at a sensitive of 10^-5 using next generation sequencing (NGS)-based method in the bone marrow.

Secondary Outcome Measures

Measure:Subject incidence of treatment-emergent adverse event
Time Frame:Up to 60 Months
Safety Issue:
Description:Describe the safety and tolerability of carfilzomib combined dexamethasone and pomalidomide.
Measure:Number of participants with negative minimal residual disease negative complete response (MRD[-]CR)
Time Frame:Up to 60 months
Safety Issue:
Description:MRD[-]CR at a sensitivity of 10^-5 using next generation sequencing (NGS)-based method in the bone marrow.
Measure:Number of participants with sustained MRD[-]CR
Time Frame:26 months
Safety Issue:
Description:Sustained MRD[-]CR response at a sensitivity of 10^-5 using NGS-based method in the bone marrow defined as subjects that maintain MRD[-]CR 12 months or more after achieving MRD[-]CR status, disregarding when the first MRD[-]CR was reached.
Measure:Number of participants with sustained MRD[-]CR
Time Frame:24 months
Safety Issue:
Description:Sustained MRD[-]CR response at a sensitivity of 10^-5 using NGS-based method in the bone marrow at 24 months ± 4 weeks from start of treatment and calculated only within the subjects who reached MRD[-]CR in the time window for primary endpoint assessment.
Measure:Overall response rate (ORR)
Time Frame:60 months
Safety Issue:
Description:Estimate overall response defined as the best overall confirmed response of partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR) by Independent Review Committee (IRC) per International Myeloma Working Group Uniform Response Criteria (IMWG-URC).
Measure:Overall response rate at 12 month landmark
Time Frame:12 months
Safety Issue:
Description:Estimate a landmark overall response by 12 months, defined as the best overall confirmed response of partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR) by 12 months from start of treatment.
Measure:Duration of response
Time Frame:From start of treatment until disease progression or death from any cause (approximately 5 years)
Safety Issue:
Description:Estimate duration of response, defined as time from first date of partial response (PR) or better to date of disease progression or death due to any cause.
Measure:Time to response
Time Frame:From start of treatment until disease progression or death from any cause (approximately 5 years)
Safety Issue:
Description:Estimate time to response, defined as time from start of treatment to first date of partial response (PR) or better.
Measure:Progression-free survival (PFS)
Time Frame:From start of treatment until disease progression or death from any cause (approximately 5 years)
Safety Issue:
Description:Estimate Progression-free survival (PFS) defined as time from start of treatment until progression or death from any cause.
Measure:Overall survival (OS)
Time Frame:From start of treatment until disease progression or death from any cause (approximately 5 years)
Safety Issue:
Description:Estomate Overall Survival (OS), defined as time from start of treatment until death from any cause.
Measure:Best overall confirmed response of complete response (CR) or better
Time Frame:Up to 60 months
Safety Issue:
Description:Estimate complete response (CR) rate of carfilzomib, pomalidomide and dexamethasone (KPd) cohort.

Details

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

Trial Keywords

  • Multiple Myeloma
  • RRMM
  • Open-label
  • First Relapse Multiple Myeloma
  • Second Relapse Multiple Myeloma
  • Refractory to Lenalidomide
  • Triplicate Treatment Regimen
  • dexamethasone
  • Carfilzomib
  • Pomalidomide

Last Updated

August 26, 2020