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

NCT03729804 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: IRB18-1243
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Number of Participants with progression free survival with the group taking KRd versus VRd after randomization

  5 years

Secondary Outcomes (4)

• The rate of MRD-negative (minimal residual disease) at indicated time points of study after randomization

  5 years

• 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

  5 years

• The combination of drugs (KRd vs VRd) safety and tolerability based on patients response

  5 years

• Evaluate the correlation between treatment outcome using KRd or VRd and pre-treatment

  5 years

Study Arms (2)

KRD Arm

EXPERIMENTAL

Patients assigned to this group will receive a combination of carfilzomib, lenalidomide, and dexamethasone in 28 day cycles. Doses will vary

Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone

VRD Arm

EXPERIMENTAL

Patients assigned to this group will receive a combination of Bortezomib, lenalidomide and dexamethasone in 21-day cycles. Doses will vary

Drug: Lenalidomide; Drug: Dexamethasone; Drug: Bortezomib

Interventions

Carfilzomib DRUG

Carfilzomib will be given by IV on Days 1, 2, 15 and 16 of each cycle during cycles 1-8. Carfilzomib will be given by IV on days 1, 2, 15 and 16 of each cycle during cycles 9-24.

Also known as: Kyprolis

KRD Arm

Lenalidomide DRUG

Lenalidomide will be taken by mouth once a day for days 1-21 of each cycle during cycles 1-8. Lenalidomide will be taken by mouth once a day for days 1-21 of each cycle for cycles 9-24.

Also known as: CC-5013, Revlimid

KRD Arm; VRD Arm

Dexamethasone DRUG

Dexamethasone will be taken by mouth on days 1, 8, 15 and 22 of each cycle during cycles 1-8. Dexamethasone will be taken by mouth on Days 1, 8, 15 and 22 of each cycle during cycles 9-24.

KRD Arm; VRD Arm

Bortezomib DRUG

Bortezomib will be give by IV on days 1, 4, 8 and 11 of each cycle during cycles 1-8.

Also known as: Velcade, PS-341

VRD Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Both transplant and non-transplant candidates are eligible. Transplant candidates must agree to defer transplant at time of consent.
• Diagnosis of symptomatic multiple myeloma as per current International Myeloma Working Group uniform criteria prior to initial treatment
• Monoclonal plasma cells in the BM 10% or presence of a biopsy-proven plasmacytoma
• 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
• 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.
• Males and females 18 years of age or older.
• Eastern Cooperative Oncology Group performance status of 0-1
• 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
• 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.
• Calculated creatinine clearance (by Cockroft-Gault) greater than or equal to 50 mL/min or serum creatinine below 2 g/dL

You may not qualify if:

• Frail non-transplant candidates, defined as in Palumbo et al, Blood 2015
• 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
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Amyloidosis
• Plasma cell leukemia
• Waldenström's macroglobulinemia or IgM myeloma
• 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)
• 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
• Potential subjects with evidence of progressive disease as per IMWG criteria
• Patients not able to tolerate daratumumab, carfilzomib, lenalidomide or dexamethasone
• Peripheral neuropathy greater than or equal to Grade 2 at screening
• Diarrhea greater than Grade 1 in the absence of antidiarrheals
• CNS involvement
• Patients who cannot undergo or unwilling to take thromoprophylaxis
• Uncontrolled or symptomatic angina, arrhythmia, hypertension, CHF, EF less than 40%, within 6 months prior to first dose

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University Of Chicago Medicine Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; Lenalidomide; Dexamethasone; Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines

Study Officials

• Andrzej Jakubowiak, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2018
• First Posted: November 5, 2018
• Study Start: May 7, 2019
• Primary Completion (Estimated): December 28, 2026
• Study Completion (Estimated): December 28, 2026
• Last Updated: March 4, 2026

Record last verified: 2026-03

Locations

US (1)