Multiple MyelomaPhase 3(COBRA)NCT03729804
Carfilzomib, Lenalidomide, and Dexamethasone Versus Bortezomib, Lenalidomide and Dexamethasone (KRd vs. VRd) in Patients With Newly Diagnosed Multiple Myeloma (COBRA)
A Phase 3 study testing Carfilzomib, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by University of Chicago at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Carfilzomib, Lenalidomide and Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 1 siteUnited States
- Study dates
- 7 May 2019to 28 Dec 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
- 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).
- 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.
- 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.
- 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®.
- Subjects must comply with pregnancy prevention and counseling
- Voluntary written informed consent.
Who cannot join
- Patients meeting any of the following exclusion criteria are not eligible to enroll in this study.
- 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
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- 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
- Pregnant or lactating females
- Major surgery within 3 weeks prior to first dose.
- 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
- Prior or concurrent pulmonary embolism
- Known moderate or severe persistent asthma or known chronic obstructive pulmonary disease (COPD)
- Rate-corrected QT interval of electrocardiograph (QTc) greater than 470 msec on a 12-lead ECG during screening
- Uncontrolled diabetes
- Acute infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
- 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.
- 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
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University Of Chicago Medicine Comprehensive Cancer Center
Chicago, Illinois, 60637
About this study
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)
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
- Being tested
- Carfilzomib, Lenalidomide, Dexamethasone, Bortezomib
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarfilzomibDrug
Also called Kyprolis
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.
LenalidomideDrug
Also called CC-5013, Revlimid
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.
DexamethasoneDrug
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.
BortezomibDrug
Also called Velcade, PS-341
Bortezomib will be give by IV on days 1, 4, 8 and 11 of each cycle during cycles 1-8.
| Study group | Role | What they receive |
|---|---|---|
| KRD Arm | Experimental | Patients assigned to this group will receive a combination of carfilzomib, lenalidomide, and dexamethasone in 28 day cycles. Doses will vary Receives: 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 Receives: Drug: Lenalidomide; Drug: Dexamethasone; Drug: Bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with progression free survival with the group taking KRd versus VRd after randomization
Measured: 5 years
Secondary outcomes (4)
The rate of MRD-negative (minimal residual disease) at indicated time points of study after randomization
Measured: 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
Measured: 5 years
The combination of drugs (KRd vs VRd) safety and tolerability based on patients response
The safety and tolerability of lenalidomide and carfilzomib will be evaluated by means of drug related Adverse Events reports.
Measured: 5 years
Evaluate the correlation between treatment outcome using KRd or VRd and pre-treatment
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2018
- Study start7 May 2019
- Primary completion28 Dec 2026 (estimated)
- Study completion28 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 250 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andrzej Jakubowiak, MD, Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03729804
- Sponsor's protocol ID
- IRB18-1243
- Acronym
- (COBRA)
- Status last verified
- Mar 2026
- First submitted
- 12 Oct 2018
- Last updated
- 4 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03729804
- Acronym / sponsor ID
- (COBRA) / IRB18-1243
- Conditions
- Multiple Myeloma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 250 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Study start
- 7 May 2019 (actual)
- Primary completion
- 28 Dec 2026 (estimated)
- Study completion
- 28 Dec 2026 (estimated)
- First posted
- 5 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| KRD Arm | Experimental | Drug: Carfilzomib, Drug: Lenalidomide, Drug: DexamethasonePatients assigned to this group will receive a combination of carfilzomib, lenalidomide, and dexamethasone in 28 day cycles. Doses will vary |
| VRD Arm | Experimental | Drug: Lenalidomide, Drug: Dexamethasone, Drug: BortezomibPatients assigned to this group will receive a combination of Bortezomib, lenalidomide and dexamethasone in 21-day cycles. Doses will vary |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Newly diagnosed, previously untreated myeloma requiring systemic chemotherapy per International Myeloma Working Group criteria:
- 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:
Key exclusion criteria (27 listed)
- Patients meeting any of the following exclusion criteria are not eligible to enroll in this study.
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarfilzomibAlso: KyprolisCarfilzomib 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. | Drug | KRD Arm |
| LenalidomideAlso: CC-5013, RevlimidLenalidomide 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. | Drug | KRD Arm, VRD Arm |
| DexamethasoneDexamethasone 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. | Drug | KRD Arm, VRD Arm |
| BortezomibAlso: Velcade, PS-341Bortezomib will be give by IV on days 1, 4, 8 and 11 of each cycle during cycles 1-8. | Drug | VRD Arm |
Primary outcome
Number of Participants with progression free survival with the group taking KRd versus VRd after randomization
Time frame: 5 years
4 secondary outcomes
The rate of MRD-negative (minimal residual disease) at indicated time points of study after randomization
Time frame: 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
Time frame: 5 years
The combination of drugs (KRd vs VRd) safety and tolerability based on patients response
Time frame: 5 years
Evaluate the correlation between treatment outcome using KRd or VRd and pre-treatment
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrzej Jakubowiak, MD principal investigator
University of Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Carfilzomib, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by University of Chicago at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with progression free survival with the group taking KRd versus VRd after randomization (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2026.