Carfilzomib, Lenalidomide, and Dexamethasone for Smoldering Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title: Carfilzomib, Lenalidomide, and Dexamethasone in High-Risk Smoldering Multiple Myeloma: a Clinical and Correlative Pilot Study

Status Active, not recruiting

Clinical Trial Summary

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.

Clinical Trial Description

Background:

Smoldering multiple myeloma (SMM) is a precursor condition to multiple myeloma (MM) defined by the clinical parameters of M-protein >= 3.0 g/dL or bone marrow plasma cells >= 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, International Myeloma Working Group (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 cyclophosphamide, lenalidomide, and dexamethasone (CRd) in patients with high-risk SMM, focusing on the

Minimal residual disease (MRD(-) Complete Response (CR) rate

Eligibility:

SMM according to the International Myeloma Working Group definition; i.e.:

Serum M-protein >=3 g/dl and/or bone marrow plasma cells >=10 % and < 60%

Absence of anemia: Hemoglobin >10 g/dl

Absence of renal failure: serum creatinine < 2.0 mg/dL.

Absence of hypercalcemia: Calcium (Ca) < 10.5 mg/dl or 2.65 mmol/L

Absence of lytic bone lesion

Involved/un-involved light chain ratio must be < 100

Measurable disease

High-risk SMM per Mayo Clinic, Spanish Programa de Estudio y Tratamiento de las Hemopatías Malignas (PETHEMA), or the Rajkumar, Landgren, Mateos criteria

Age >=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 serum protein electrophoresis (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 fluorodeoxyglucose (FDG)-positron emission tomography (PET)-computed tomography (CT)

This single arm pilot study will plan on initially enrolling 12 evaluable patients to detect a very good partial response (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. ;

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Smoldering Multiple Myeloma

• NCT number: NCT01572480
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 29, 2012
• Completion date: June 1, 2028