Multiple Myeloma
Conditions
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.
Interventions
DRUGCarfilzomib
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.
DRUGLenalidomide
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.
DRUGDexamethasone
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.
DRUGBortezomib
Bortezomib will be give by IV on days 1, 4, 8 and 11 of each cycle during cycles 1-8.
Sponsors
University of Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants with progression free survival with the group taking KRd versus VRd after randomization | 5 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | The safety and tolerability of lenalidomide and carfilzomib will be evaluated by means of drug related Adverse Events reports. |
| Evaluate the correlation between treatment outcome using KRd or VRd and pre-treatment | 5 years | — |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAndrzej Jakubowiak, MD
University of Chicago
Outcome results
None listed