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