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A Study Comparing Once-weekly vs Twice-weekly Carfilzomib in Combination With Lenalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

NCT03859427

Description:

Compare efficacy of 56 mg/m2 carfilzomib administered once-weekly in combination with lenalidomide and dexamethasone (KRd 56 mg/m2) to 27 mg/m2 carfilzomib administered twice-weekly in combination with lenalidomide and dexamethasone (KRd 27 mg/m2) in subjects with relapsed or refractory multiple myeloma (RRMM) with 1 to 3 prior lines of therapy.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study Comparing Once-weekly vs Twice-weekly Carfilzomib in Combination With Lenalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
  • Official Title: A Randomized, Open-label, Phase 3 Study Comparing Once-weekly vs Twice-weekly Carfilzomib in Combination With Lenalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (A.R.R.O.W.2)

Clinical Trial IDs

  • ORG STUDY ID: 20180015
  • NCT ID: NCT03859427

Conditions

  • Relapsed or Refractory Multiple Myeloma

Interventions

DrugSynonymsArms
CarfilzomibCarfilzomib once-weekly
CarfilzomibCarfilzomib twice-weekly
LenalidomideCarfilzomib once-weekly
DexamethasoneCarfilzomib once-weekly

Purpose

Compare efficacy of 56 mg/m2 carfilzomib administered once-weekly in combination with lenalidomide and dexamethasone (KRd 56 mg/m2) to 27 mg/m2 carfilzomib administered twice-weekly in combination with lenalidomide and dexamethasone (KRd 27 mg/m2) in subjects with relapsed or refractory multiple myeloma (RRMM) with 1 to 3 prior lines of therapy.

Trial Arms

NameTypeDescriptionInterventions
Carfilzomib once-weeklyActive ComparatorCarfilzomib, lenalidomide, dexamethasone (KRd) regimen using once-weekly carfilzomib 56 mg/m2
  • Carfilzomib
  • Lenalidomide
  • Dexamethasone
Carfilzomib twice-weeklyActive ComparatorCarfilzomib, lenalidomide, dexamethasone (KRd) regimen using twice-weekly carfilzomib 27 mg/m2
  • Carfilzomib
  • Lenalidomide
  • Dexamethasone

Eligibility Criteria

        Inclusion Criteria:

        Documented relapse or progressive multiple myeloma on or after any treatment (subjects
        refractory to the most recent line of therapy are eligible, unless last treatment contained
        PI or lenalidomide and dexamethasone).

        Subjects must have at least PR to at least 1 line of prior therapy.

        Subjects must have received at least 1 but not more than 3 prior lines of therapy for
        multiple myeloma (induction therapy followed by stem cell transplant and consolidation
        maintenance therapy will be considered as 1 line of therapy).

        Prior therapy with a PI or the combination of lenalidomide and dexamethasone are allowed,
        if, the patient had at least a PR to the most recent therapy with a PI or lenalidomide and
        dexamethasone, neither PI or lenalidomide and dexamethasone in combination were ceased due
        to toxicity, the patient has not received a PI and has not received lenalidomide and
        dexamethasone in combination in the 6 months prior to first study treatment. (Patients are
        permitted to have received single agent lenalidomide as maintenance therapy during the 6
        months prior to first treatment)

        Previous treatment with a lenalidomide and dexamethasone containing regimen is allowed, as
        long as the subject did not progress during the first 3 months after initiating
        lenalidomide and dexamethasone containing therapy.

        Measurable disease with at least 1 of the following assessed within 21 days prior to
        randomization:

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

          -  Inmunoglobulin A (IgA), Inmunoglobulin D (IgD), Inmunoglobulin E (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

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

        Other inclusion criteria may apply

        Exclusion Criteria:

        Waldenström macroglobulinemia.

        Multiple myeloma of Inmunoglobulin M (IgM) subtype.

        Plasma cell leukemia (> 2.0 × 10^9 /L circulating plasma cells by standard differential).

        Uncontrolled hypertension, defined as an average systolic blood pressure ≥ 160 mmHg or
        diastolic ≥ 100 mmHg despite optimal treatment (blood pressure to be measured following
        European Society of Hypertension/European Society of Cardiology 2013 guidelines).

        Active congestive heart failure (New York Heart Association Class III to IV), symptomatic
        ischemia, uncontrolled arrhythmias, screening ECG with corrected QT interval (QTc) of > 470
        msec, pericardial disease, or myocardial infarction within 4 months prior to randomization.

        Calculated or measured creatinine clearance < 1.0 mL/s (calculation must be based on the
        Cockcroft and Gault formula) within 21 days prior to randomization.

        Other exclusion criteria may apply
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:Through study completion, an average of 14 months
Safety Issue:
Description:ORR defined as the proportion of best overall response of stringent complete response [sCR], complete response [CR], very good partial response [VGPR] and partial response [PR] per International Myeloma Working Group Uniform Response Criteria [IMWG-URC]

Secondary Outcome Measures

Measure:1-year Progression free survival
Time Frame:1 year
Safety Issue:
Description:
Measure:Convenience
Time Frame:Through study completion, an average of 14 months
Safety Issue:
Description:As measured by the Patient-reported convenience with carfilzomib dosing schedule question
Measure:Subject incidence of treatment-emergent adverse events
Time Frame:Through study completion, an average of 14 months
Safety Issue:
Description:
Measure:Additional efficacy parameter - Time to Response
Time Frame:Through study completion, an average of 14 months
Safety Issue:
Description:As measured by Time to Response (TTR)
Measure:Additional efficacy parameter - Duration of Response
Time Frame:Through study completion, an average of 14 months
Safety Issue:
Description:Duration of Response (DOR)
Measure:Additional efficacy parameter - Time to Progression
Time Frame:Through study completion, an average of 14 months
Safety Issue:
Description:Time to Progression (TTP)
Measure:1-year Overall Survival
Time Frame:1 year
Safety Issue:
Description:
Measure:MRD[-]CR rate
Time Frame:Through study completion, an average of 14 months
Safety Issue:
Description:Defined as achievement of CR or better by Independent Review Committee (IRC) per IMWG-URC and achievement of Minimal Residual Disease (MRD) negativity as assessed by next-generation sequencing method at a 10^ -5 threshold
Measure:MRD[-] rate at 12 months
Time Frame:12 months
Safety Issue:
Description:Defined as achievement of Minimal Residual Disease (MRD) negativity at 12 months (+/- 2 weeks) from randomisation as assessed by next-generation sequencing method at a 10^ -5 threshold
Measure:Physical functioning and role functioning
Time Frame:Through study completion, an average of 14 months
Safety Issue:
Description:As measured by the Physical Functioning and Role Functioning scales of the European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30), a 30-item generic instrument for use in cancer subjects across tumor types
Measure:Treatment satisfaction as measured by the Satisfaction with Therapy (SWT) subscale of the Cancer Therapy Satisfaction Questionnaire (CTSQ)
Time Frame:4 months
Safety Issue:
Description:Cancer Therapy Satisfaction Questionnaire (CTSQ) - measures treatment satisfaction in individuals with cancer

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Amgen

Trial Keywords

  • Bone Marrow Cancer

Last Updated

December 18, 2019