Clinical Trials /

Carfilzomib, Lenalidomide, and Dexamethasone Versus Bortezomib, Lenalidomide and Dexamethasone (KRd vs. VRd) in Patients With Newly Diagnosed Multiple Myeloma (COBRA)

NCT03729804

Description:

This is a randomized multicenter study that will compare two treatment regimens (Kyprolis, Revlimid, dexamethasone -KRD vs. Velcade, Revlimid, dexamethasone -VRD) for patients with newly diagnosed multiple myeloma.

Related Conditions:
  • Multiple Myeloma
  • Plasmacytoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Carfilzomib, Lenalidomide, and Dexamethasone Versus Bortezomib, Lenalidomide and Dexamethasone (KRd vs. VRd) in Patients With Newly Diagnosed Multiple Myeloma (COBRA)
  • Official Title: A Randomized, Open-label Phase 3 Study of Carfilzomib, Lenalidomide, and Dexamethasone Versus Bortezomib, Lenalidomide and Dexamethasone (KRd vs. VRd) in Patients With Newly Diagnosed Multiple Myeloma (COBRA)

Clinical Trial IDs

  • ORG STUDY ID: IRB18-1243
  • NCT ID: NCT03729804

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
CarfilzomibKyprolisKRD Arm
LenalidomideCC-5013, RevlimidKRD Arm
DexamethasoneKRD Arm
BortezomibVelcade, PS-341VRD Arm

Purpose

This is a randomized multicenter study that will compare two treatment regimens (Kyprolis, Revlimid, dexamethasone -KRD vs. Velcade, Revlimid, dexamethasone -VRD) for patients with newly diagnosed multiple myeloma.

Trial Arms

NameTypeDescriptionInterventions
KRD ArmExperimentalPatients assigned to this group will receive a combination of carfilzomib, lenalidomide, and dexamethasone in 28 day cycles. Doses will vary
  • Carfilzomib
  • Lenalidomide
  • Dexamethasone
VRD ArmExperimentalPatients assigned to this group will receive a combination of Bortezomib, lenalidomide and dexamethasone in 21-day cycles. Doses will vary
  • Lenalidomide
  • Dexamethasone
  • Bortezomib

Eligibility Criteria

        Inclusion Criteria:

          1. Newly diagnosed, previously untreated myeloma requiring systemic chemotherapy per
             International Myeloma Working Group criteria:

             • Patients must have received no prior chemotherapy for this disease; patients must
             have received no prior radiotherapy to a large area of the pelvis (more than half of
             the pelvis); prior steroid treatment is allowed provided treatment was not more than 2
             weeks in duration and less than or equal to 160 mg dexamethasone; patients must not
             have received any prior treatment with bortezomib or lenalidomide

          2. Both transplant and non-transplant candidates are eligible. Transplant candidates must
             agree to defer transplant at time of consent.

          3. Diagnosis of symptomatic multiple myeloma as per current International Myeloma Working
             Group uniform criteria prior to initial treatment

          4. Monoclonal plasma cells in the BM 10% or presence of a biopsy-proven plasmacytoma

          5. Measurable disease, prior to initial treatment as indicated by one or more of the
             following:

               -  Serum M-protein greater than or equal to 1 g/dL

               -  Urine M-protein greater than or equal to 200 mg/24 hours

               -  If serum protein electrophoresis is felt to be unreliable for routine M-protein
                  measurement, then quantitative immunoglobulin levels are acceptable

          6. Bone marrow specimen will be required at study entry; available DNA sample from
             pre-induction BM will be used for calibration step for Minimal Residual Disease
             evaluation by gene sequencing.

          7. Males and females 18 years of age or older.

          8. Eastern Cooperative Oncology Group performance status of 0-1

          9. Adequate hepatic function, with bilirubin less than or equal to 1.5 x ULN and aspirate
             aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x
             ULN

         10. ANC greater than or equal to 1.0 x 109/L, hemoglobin greater than or equal to 8 g/dL,
             platelet count greater than or equal to 75 x 109/L.

         11. Calculated creatinine clearance (by Cockroft-Gault) greater than or equal to 50 mL/min
             or serum creatinine below 2 g/dL

         12. 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).

         13. 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 30 days after discontinuation from the
             study.

         14. 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 90 days
             following discontinuation from the study even if he has undergone a successful
             vasectomy.

         15. 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®.

         16. Subjects must comply with pregnancy prevention and counseling

         17. Voluntary written informed consent.

        Exclusion Criteria:

        Patients meeting any of the following exclusion criteria are not eligible to enroll in this
        study.

          1. Frail non-transplant candidates, defined as in Palumbo et al, Blood 2015

          2. Non-secretory or hyposecretory multiple myeloma, prior to initial treatment defined as
             less than 1.0 g/dL M-protein in serum, less than 200 mg/24 hr urine M-protein

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

          4. Amyloidosis

          5. Plasma cell leukemia

          6. Waldenström's macroglobulinemia or IgM myeloma

          7. Radiotherapy to multiple sites or immunotherapy within 4 weeks before start of
             protocol treatment (localized radiotherapy to a single site at least 1 week before
             start is permissible)

          8. Participation in an investigational therapeutic study within 3 weeks or within 5 drug
             half-lives (t1/2) prior to first dose, whichever time is greater

          9. Potential subjects with evidence of progressive disease as per IMWG criteria

         10. Patients not able to tolerate daratumumab, carfilzomib, lenalidomide or dexamethasone

         11. Peripheral neuropathy greater than or equal to Grade 2 at screening

         12. Diarrhea greater than Grade 1 in the absence of antidiarrheals

         13. CNS involvement

         14. Patients who cannot undergo or unwilling to take thromoprophylaxis

         15. Uncontrolled or symptomatic angina, arrhythmia, hypertension, CHF, EF less than 40%,
             within 6 months prior to first dose

         16. Pregnant or lactating females

         17. Major surgery within 3 weeks prior to first dose.

         18. 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

         19. Prior or concurrent pulmonary embolism

         20. Known moderate or severe persistent asthma or known chronic obstructive pulmonary
             disease (COPD)

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

         22. Uncontrolled diabetes

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

         24. 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.

         25. 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 less than Gleason Grade 6
             with stable prostate specific antigen levels or cancer considered cured by surgical
             resection alone

         26. Any clinically significant medical disease or condition that, in the 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:Number of Participants with progression free survival with the group taking KRd versus VRd after randomization
Time Frame:5 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:The rate of MRD-negative (minimal residual disease) at indicated time points of study after randomization
Time Frame:5 years
Safety Issue:
Description:
Measure:The combination of drugs (KRd vs VRd) with the best response using minimal residual disease analysis across entire treatment in high risk and low risk patients
Time Frame:5 years
Safety Issue:
Description:
Measure:The combination of drugs (KRd vs VRd) safety and tolerability based on patients response
Time Frame:5 years
Safety Issue:
Description:The safety and tolerability of lenalidomide and carfilzomib will be evaluated by means of drug related Adverse Events reports.
Measure:Evaluate the correlation between treatment outcome using KRd or VRd and pre-treatment
Time Frame:5 years
Safety Issue:
Description:

Details

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

Last Updated

June 21, 2019