Carfilzomib, Lenalidomide, and Dexamethasone for Smoldering Multiple Myeloma

Summary

Participation Requirements

Description

BACKGROUND: SMM is a precursor condition to MM defined by the clinical parameters of M-protein greater than or equal to 3.0 g/dL or bone marrow plasma cells greater than or equal to 10% and absence of end organ disease. Risk of progression of high risk SMM at 5 years is 72-75% with median time to pr...

BACKGROUND: SMM is a precursor condition to MM defined by the clinical parameters of M-protein greater than or equal to 3.0 g/dL or bone marrow plasma cells greater than or equal to 10% and absence of end organ disease. Risk of progression of high risk SMM at 5 years is 72-75% with median time to progression <2 years. The current standard of care for SMM is close follow-up without treatment until symptomatic MM develops. However, IMWG states "Preventive clinical trials need to be considered for patients with high risk smoldering myeloma". - Carfilzomib is a new proteasome inhibitor with potent anti-MM effects OBJECTIVES: - To assess the response rate of CRd in patients with high-risk SMM, focusing on the MRD(-) CR rate ELIGIBILITY: SMM according to the International Myeloma Working Group definition i.e.: Serum M-protein greater than or equal to 3 g/dl and/or bone marrow plasma cells greater than or equal to 10 % and less than 60%, Absence of anemia: Hemoglobin >10 g/dl Absence of renal failure: serum creatinine < 2.0 mg/dL. Absence of hypercalcemia: Ca <10.5 mg/dl or 2.65 mmol/L Absence of lytic bone lesion Involved/un-involved light chain ratio must be less than 100 Measurable disease as defined in the protocol 'High-risk SMM' per Mayo Clinic, Spanish PETHEMA, or the Rajkumar, Landgren Mateos criteria Age greater than or equal to 18 years Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Adequate laboratory parameters as defined in the protocol DESIGN: - Single arm pilot trial of combination therapy (carfilzomib, lenalidomide, and dexamethasone) for high risk smoldering multiple myeloma Patients will receive 8 cycles of induction combination therapy of CRd Each cycle consists of 28-days After 4 cycles of therapy, transplant eligible patients may choose to undergo stem cell collection After 8 cycles of CRd, patients will receive lenalidomide extended dosing (phase I) for 12 cycles. After 12 cycles, patients will have the option to continue extended dosing (phase II) for one additional year. Patients will have routine blood work with SPEP and free light chains monthly during the induction phase. Laboratory evaluations may be spread out to every 3 months during the maintenance and follow-up phases. Pre-treatment, post-treatment and follow-up bone marrow biopsies will be obtained for confirmation of diagnosis, response and correlative studies Patients will also undergo evaluation for minimal residual disease at regular interval time points, using multi-parametric flow cytometry and FDG PET-CT This single arm pilot study will plan on initially enrolling 12 evaluable patients to detect a VGPR from baseline. A replicate cohort of 16 evaluable patients will then be enrolled in order to more precisely define the response rate to the CRd regimen in this population. Accrual will then be extended to a total of 50 evaluable patients in order to estimate the MRD(-) CR rate with reasonable precision. To allow for a number of inevaluable patients, and screen failures the accrual ceiling will be set at 63.

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