Clinical Trials /

Trial of Carfilzomib, Lenalidomide, Dexamethasone Versus Lenalidomide Alone After Stem-cell Transplant for Multiple Myeloma

NCT02659293

Description:

This is a Phase 3 randomized trial of carfilzomib, lenalidomide, dexamethasone versus lenalidomide alone after stem-cell transplant for multiple myeloma, eligible to subjects who completed autologous stem cell transplant for symptomatic myeloma who are considered for lenalidomide maintenance.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Trial of Carfilzomib, Lenalidomide, Dexamethasone Versus Lenalidomide Alone After Stem-cell Transplant for Multiple Myeloma
  • Official Title: Phase 3 Randomized Trial of Carfilzomib, Lenalidomide, Dexamethasone Versus Lenalidomide Alone After Stem-cell Transplant for Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: IRB15-1286
  • NCT ID: NCT02659293

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
LenalidomideRevlimidExperimental Combination Regimen
CarfilzomibKyprolisExperimental Combination Regimen
DexamethasoneExperimental Combination Regimen
Lenalidomide (Control)RevlimidLenalidomide (Control)

Purpose

This is a Phase 3 randomized trial of carfilzomib, lenalidomide, dexamethasone versus lenalidomide alone after stem-cell transplant for multiple myeloma, eligible to subjects who completed autologous stem cell transplant for symptomatic myeloma who are considered for lenalidomide maintenance.

Detailed Description

      Primary Objective:

        -  To compare progression free survival between Kyprolis (Carfilzomib), Revlimid
           (lenalidomide), Dexamethasone (KRd) arm and lenalidomide arm

      Secondary Objectives

        -  To determine the rate of minimal residual negative disease (MRD) at 6 and 12 months
           after randomization

        -  To compare the efficacy (rate of partial response, very good partial response, complete
           response, and stringent complete response) of KRd vs. Lenalidomide alone after
           randomization
    

Trial Arms

NameTypeDescriptionInterventions
Lenalidomide (Control)Active ComparatorTreatment with lenalidomide only
  • Lenalidomide (Control)
Experimental Combination RegimenExperimentalExperimental arm using a combination of Carfilzomib, Lenalidomide and Dexamethasone
  • Lenalidomide
  • Carfilzomib
  • Dexamethasone

Eligibility Criteria

        Inclusion Criteria:

          1. Patients who completed single autologous stem cell transplant after completion of at
             most 2 induction regimens (excluding dexamethasone alone) and are in at least stable
             disease in the first 100 days after stem cell transplantation.

          2. Patients must be within 12 months of initiation of induction therapy and must have had
             not more than 2 prior induction regimens.

          3. Bone marrow specimen will be required at study entry; available DNA sample will be
             used for calibration step for MRD evaluation by gene sequencing.

          4. Males and females ≥ 18 years of age

          5. ECOG performance status of 0-1

          6. Adequate hepatic function, with bilirubin ≤ 1.5 x ULN and aspirate aminotransferase
             (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN

          7. ANC ≥ 1.0 x 109/L, hemoglobin ≥ 8 g/dL, platelet count ≥ 75 x 109/L.

          8. Calculated creatinine clearance (by Cockcroft-Gault) ≥ 50 ml/min or serum creatinine
             below 2 mg/dL

          9. Females of childbearing potential (FCBP) must have 2 negative pregnancy tests
             (sensitivity of at least 50 mIU/mL) prior to initiating lenalidomide. The first
             pregnancy test must be performed within 10-14 days before and the second pregnancy
             test must be performed within 24 hours before lenalidomide is prescribed for Cycle 1
             (prescriptions must be filled within 7 days).

         10. FCBP must agree to use 2 reliable forms of contraception simultaneously or to practice
             complete abstinence from heterosexual intercourse during the following time periods
             related to this study: 1) for at least 28 days before starting lenalidomide; 2) while
             participating in the study; and 3) for at least 28 days after discontinuation from the
             study.

             UCM IRB CRd vs. R Version 1.0 Page 11

         11. Male subjects must agree to use a latex condom during sexual contact with females of
             childbearing potential while participating in the study and for at least 28 days
             following discontinuation from the study even if he has undergone a successful
             vasectomy.

         12. All study participants in the US must be consented to and registered into the
             mandatory Revlimid REMS® program and be willing and able to comply with the
             requirements of Revlimid REMS®.

         13. Voluntary written informed consent

        Exclusion Criteria:

          1. Patients who have had more than 12 months of prior therapy. Patients outside of this
             window may be considered for inclusion on a case-by-case basis.

          2. Patients who progressed after initial therapy.

               1. Subjects whose therapy changed due to suboptimal response, intolerance, etc.,
                  remain eligible, provided they do not meet criteria for progression.

               2. No more than two regimens for induction will be allowed excluding dexamethasone
                  alone.

          3. Evidence of progressive disease as per International Myeloma Working Group (IMWG)
             criteria

          4. Patients who have already started or received post-transplant maintenance or
             consolidation regimen

          5. Patients not able to tolerate lenalidomide or carfilzomib or dexamethasone

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

          7. Plasma cell leukemia

          8. Waldenström's macroglobulinemia or IgM myeloma

          9. Peripheral neuropathy ≥ Grade 2 at screening

         10. Diarrhea > Grade 1 in the absence of antidiarrheals

         11. CNS involvement

         12. Pregnant or lactating females

         13. Radiotherapy within 14 days before randomization. Seven days may be considered if to
             single area.

         14. Major surgery within 3 weeks prior to first dose

         15. Myocardial infarction within 6 months prior to enrollment, NYHA Class III or IV heart
             failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or
             electrocardiographic evidence of acute ischemia or active conduction system
             abnormalities

         16. Prior or concurrent deep vein thrombosis or pulmonary embolism

         17. Rate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12-lead ECG
             during screening

         18. Uncontrolled hypertension or diabetes

         19. Acute infection requiring systemic antibiotics, antivirals, or antifungals within two
             weeks prior to first dose

         20. Known seropositive for or active viral infection with human immunodeficiency virus
             (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are
             seropositive because of hepatitis B virus vaccine are eligible.

         21. Non-hematologic malignancy or non-myeloma hematologic malignancy within the past 3
             years except a) adequately treated basal cell, squamous cell skin cancer, thyroid
             cancer, carcinoma in situ of the cervix, or prostate cancer < Gleason Grade 6 with
             stable prostate specific antigen levels or cancer considered cured by surgical
             resection alone

         22. Any clinically significant medical disease or condition that, in the Treating
             Investigator's opinion, may interfere with protocol adherence or a subject's ability
             to give informed consent
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival rates in participants receiving drug combination
Time Frame:4 years
Safety Issue:
Description:Measurement of time to disease worsening as measured by International Myeloma Working Group (IMWG) response criteria.

Secondary Outcome Measures

Measure:Rate of minimal residual negative disease (MRD) in participants receiving drug combination
Time Frame:3 years
Safety Issue:
Description:Calculation of number of participants with MRD-negative disease.
Measure:Response rate in participants receiving drug combination
Time Frame:3 years
Safety Issue:
Description:Number of participants with disease response (e.g. improvement) as measured by International Myeloma Working Group (IMWG) response criteria.
Measure:Treatment-related side effects
Time Frame:From date of screening until end of treatment
Safety Issue:
Description:Number of participants with grade 2 or greater treatment-related side effects as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.0

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Chicago

Trial Keywords

  • Multiple myeloma
  • stem-cell transplant
  • Symptomatic myeloma
  • lenalidomide
  • carfilzomib
  • dexamethasone

Last Updated

October 7, 2019