Research study to comparison the effectivenes of combination of drugs called lenalidomide, carfilzomib, dexamethasone with combination of drugs called lenalidomide, bortezomib, dexamethasone, given to patients with newly diagnosed multiple myeloma

Trial details

Who runs it

Polish Myeloma Consortium

Trial code

EU 2024-518473-34-00

Record updated

2026. október 16.

Original description

To compare the MRD-negative complete response status at 12 months after randomization and PFSRead full original descriptionShow less

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)

To compare the MRD-negative complete response status at 12 months after randomization and PFS

Inclusion: Newly diagnosed, previously untreated myeloma requiring systemic chemotherapy per IMWG 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 ≤ 160 mg dexamethasone; • patients must not have received any prior treatment with bortezomib or lenalidomide; ANC ≥ 1.0 x 109/L, hemoglobin ≥ 8 g/dL, platelet count ≥ 75 x 109/L; Calculated creatinine clearance (by Cockroft-Gault) ≥ 50 mL/min or serum creatinine below 2 g/dL; Female of child bearing 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); 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. In addition, FCBP receiving bortezomib must use effective contraceptive measures and avoid becoming pregnant while receiving bortezomib and for 8 months following completion of bortezomib treatment; 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. In addition, male subjects receiving bortezomib must use effective contraceptive measures and be advised not to father a child while receiving bortezomib and for 5 months following completion of bortezomib treatment; All study participants in the US and EU countries (excluding Poland) 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; Both transplant and non-transplant candidates are eligible. Transplant candidates must agree at time of consent to defer transplant to the end of study treatment. If patient proceeds to transplant, they will come off study; Diagnosis of symptomatic multiple myeloma as per current IMWG 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 ≥ 1 g/dL • Urine M-protein ≥ 200 mg/24 hours • Involved serum free light chains ≥ 10 mg/dL provided that free light chain ratio is abnormal • 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-treatment BM will be used for calibration step for MRD evaluation by gene sequencing; Males and females ≥ 18 years of age; ECOG performance status of 0-2; Adequate hepatic function, with bilirubin ≤ 1.5 x ULN and aspirate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 xULN.

Exclusion: Uncontrolled or symptomatic angina, arrhythmia, hypertension, CHF, EF< 40%, within 6 months prior to first dose; 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; Pulmonary embolism within 6 months prior to first dose; Acute infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose; 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; Patients not able to tolerate bortezomib, carfilzomib, lenalidomide or dexamethasone; Known moderate or severe persistent asthma or known chronic obstructive pulmonary disease (COPD); Uncontrolled diabetes; 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 or are asymptomatic chronic carriers of HBV 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 < 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; POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes); Non-secretory or hyposecretory multiple myeloma, prior to initial treatment defined as <1.0 g/dL M-protein in serum, <200 mg/24 hr urine M-protein and and FLC <10mg/dL as per IMWG measured by Freelite; Rate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12-lead ECG during screening; Frail, non-transplant candidates, per modified IMWG frailty score (age not counted as a scoring factor); Peripheral neuropathy ≥ Grade 2 at screening; Diarrhea > Grade 1 in the absence of antidiarrheals; CNS involvement; Patients who cannot undergo or unwilling to take thromboprophylaxis; Pregnant or lactating females; Amyloidosis; Plasma cell leukemia; Waldenström’s macroglobulinemia or IgM myeloma.

EU CTIS 2024-518473-34-00