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.
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)
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.
- 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
- Monotypic plasma cell S-phase >= 1%
- 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
- Prior treatment with any other agent that may affect M-protein =< 30 days prior to
- 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
- Any of the following:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate
- 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