Last updated on April 2020

Carfilzomib Lenalidomide and Dexamethasone for Smoldering Multiple Myeloma


Brief description of study

Background
  • Multiple myeloma is a blood cancer that affects the plasma cells. These cells help produce antibodies and fight infection. Smoldering multiple myeloma (SMM) is a related condition that may develop into multiple myeloma. The current standard of care for SMM is close follow-up without treatment until multiple myeloma develops. However, researchers are studying possible treatments for SMM itself. One possible treatment involves a combination of cancer treatment drugs.
  • Lenalidomide is a drug that may help reduce or prevent the growth of cancer cells. Dexamethasone is a steroid that is often given with other anti-cancer drugs. These two drugs are an approved treatment for multiple myeloma that has not responded to at least one other treatment. Carfilzomib is an experimental drug that has been effective in treating multiple myeloma. Researchers want to combine these three drugs to see if they are a safe and effective treatment for SMM.
    Objectives
  • To see if carfilzomib, lenalidomide, and dexamethasone are a safe and effective treatment for smoldering multiple myeloma.
    Eligibility
  • Individuals at least 18 years of age who have SMM that is likely to progress to multiple myeloma.
    Design
  • Participants will be screened with a physical exam and medical history. They will also have blood and urine tests, and baseline bone marrow scans. Bone marrow samples will also be collected.
  • Participants will have eight 28-day cycles of treatment with the three study drugs. The drugs will be given as tablets or as infusions. Treatment will be monitored with frequent blood tests and study visits.
  • After the first four cycles, participants who are eligible for a stem cell transplant will have their stem cells collected and stored for future use.
  • At the end of eight cycles, participants whose disease has not progressed will have up to 12 more cycles of treatment with lenalidomide tablets alone.

Detailed Study 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 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. Beginning with Amendment L, accrual will 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, the accrual ceiling will be set at 63.

Clinical Study Identifier: NCT01572480

Find a site near you

Start Over