Lenalidomide and Dexamethasone With or Without Anakinra in Treating Patients With Early Stage Multiple Myeloma

Phase I/II Double Blind Randomized Trial of Lenalidomide/Dexamethasone/Anakinra vs. Lenalidomide/Dexamethasone/Placebo in Patients With Early Stage Multiple Myeloma and High Plasma Cell Growth Rate

This partially randomized phase I/II trial studies the side effects and best dose of anakinra when given together with lenalidomide and dexamethasone in treating patients with early stage multiple myeloma. Biological therapies, such as lenalidomide and anakinra, may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether lenalidomide and dexamethasone are more effective with or without anakinra in treating patients with multiple myeloma.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD)/maximum allowable dose (MAD) of anakinra that can be combined with lenalidomide and dexamethasone. (Phase I) II. To compare the time to progression of the standard treatment arm (lenalidomide/dexamethasone) to the experimental arm (lenalidomide/dexamethasone + anakinra). (Phase II)

SECONDARY OBJECTIVES:

I. To compare the response rate of the standard treatment arm (lenalidomide/dexamethasone) to the experimental arm (lenalidomide/dexamethasone + anakinra).

II. To compare the toxicity of the standard treatment arm (lenalidomide/dexamethasone) to the experimental arm (lenalidomide/dexamethasone + anakinra).

III. To compare the overall survival of the standard treatment arm (lenalidomide/dexamethasone) to the experimental arm (lenalidomide/dexamethasone + anakinra).

OUTLINE: This is a phase I, dose-escalation study of anakinra followed by a phase II study.

PHASE I: Patients receive lenalidomide orally (PO) on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Patients also receive anakinra subcutaneously (SC) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive lenalidomide PO on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Patients also receive anakinra SC on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive lenalidomide and dexamethasone as in Arm A. Patients also receive placebo SC on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Inclusion Criteria:

• Absolute neutrophil count (ANC) >= 1700/mm^3

• Platelet count >= 100,000/mm^3

• Hemoglobin >= 8.0 g/dL

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x upper limit of normal (ULN)

• Creatinine clearance >= 30 mL/min (as determined by Cockroft-Gault equation)

• Diagnosis of multiple myeloma according to International Myeloma Working Group criteria and one of the following:

  • Smoldering multiple myeloma (SMM)
  • Indolent multiple myeloma (IMM)
  • Newly diagnosed multiple myeloma (MM)
  • Note: patients with lytic disease and anemia are eligible

• High risk disease defined by all of the following:

  • >= 10% bone marrow plasma cells AND
  • Abnormal serum free light chain (FLC) ratio (< 0.26 or > 1.65) by serum FLC assay AND
  • Monotypic plasma cell S-phase >= 0.3%

• Measurable level of M-protein > 1 g/dL on serum protein electrophoresis or > 200 mg of M-protein on a 24 hour urine protein electrophoresis

• Negative tuberculosis (TB) testing (Quantiferon - TB blood test or skin test) =< 7 days prior to registration

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

• Provide signed informed consent

• Negative (serum or urine) pregnancy test done =< 7 days prior to registration, for women of childbearing potential only; NOTE: a second pregnancy test must be performed within 24 hours prior to the start of lenalidomide; the subject may not receive lenalidomide until the study doctor has verified that the results of these pregnancy tests are negative

• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)

• Willing and able to comply with the requirements of the Revlimid Risk Evaluation and Mitigation Strategy (REMS) program

• Females of childbearing potential must be willing to adhere to the scheduled pregnancy testing as required by the Revlimid REMS program

Exclusion Criteria:

• Prior treatment with any other agent that may affect M-protein =< 30 days prior to registration

• Acute/chronic infections, open wounds, or any active infection requiring intravenous antibiotic therapy =< 12 weeks prior to registration

• Other active malignancy (=< 3 years) prior to registration; exceptions: basal cell skin cancer or carcinoma-in-situ of the cervix or low-risk prostate cancer after curative therapy

• Any of the following:

  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception

• New York Heart Association (NYHA) class 3 or 4 congestive heart failure (CHF) symptoms

• Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational; NOTE: bisphosphonates are allowed while on protocol treatment