Study of Ibrutinib in Combination With Revlimid/Dexamethasone in Relapsed/Refractory Multiple Myeloma

Inclusion Criteria

• Men and women ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Appendix I).
• Symptomatic multiple myeloma (MM) (as defined by revised IMWG criteria) with measurable disease, defined here as having at least one of the following:
• Serum monoclonal protein ≥ 0.5 g/dL
• ≥200 mg of monoclonal protein in the urine on 24 hour electrophoresis
• Serum immunoglobulin free light chain (FLC): involved FLC ≥ 10 mg/dL (≥ 100 mg/L) AND abnormal serum immunoglobulin kappa to lambda free light chain ratio.
• At least 1 prior therapy with demonstrated disease progression following the most recent line of treatment.
• Progression of disease within 60 days of completion of last therapeutic regimen or the failure to achieve minimal response while on last treatment (according to IMWG).
• Patients should not have progressed on lenalidomide at a dose of more than 10mg
• No prior treatment with ibrutinib or any other protein kinase inhibitory drug or drug targeting the b-cell receptor (BCR) signal transduction pathway.
• Patients with prior daratumumab and allogeneic stem cell transplant are included.
• PT/INR 30 ml/min based on either the estimated Glomerular Filtration Rate (Crockcoft Gault) or measured GFR from 24-hour urine sample. Study participants with GFR 30-50 ml/min will be treated according to manufacturer's instruction with lenalidomide 10mg rather than 25 mg.
• Ability to understand and willingness to sign a written informed consent form (ICF).
• Ability to adhere with the study visit schedule and other protocol procedures.
• A negative pregnancy test will be required for all women of child bearing potential within 7 days prior to registration. Breast feeding is not permitted.
• Fertility requirements
• Female patients with child bearing potential must have a negative pregnancy test at least 7 days before starting treatment drugs.
• Male subject must use an effective barrier method of contraception during the study and for 3 months following the last dose if sexually active with a female of childbearing potential.
• Female patients must be either post-menopausal, free from menses ≥ 2yrs, surgically sterilized, willing to use two adequate barrier methods of contraception to prevent pregnancy, or agree to abstain from sexual activity starting from screening and for 90 days after lenalidomide treatment
• Female patients of childbearing potential must agree to comply with the fertility and pregnancy test requirements dictated by the Rev-Assist program.
• Willingness to provide blood and tissue samples for correlative research purposes

Exclusion Criteria

• Prior history of: Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome, osteosclerotic myeloma, Crow-Fukase syndrome, primary amyloidosis or plasma cell leukemia.
• Radiotherapy within 21 days of registration. However, if the radiation portal was localized to single lesion or fracture site and covered by ≤ 5% of the bone marrow reserve (by investigator estimate), the subject may be enrolled irrespective of the end date of radiotherapy.
• Prior chemotherapy:
• Alkylators (e.g. melphalan, cyclophosphamide) ≤ 21 days prior to registration and/or monoclonal antibody ≤ 6 weeks prior to first administration of study treatment.
• Anthracyclines ≤ 21 days prior to registration.
• High dose corticosteroids, immune modulatory drugs (thalidomide or lenalidomide), or proteasome inhibitors (bortezomib or carfilzomib) ≤ 14 days prior to registration.
• No concomitant high dose corticosteroids (concurrent use of corticosteroids). EXCEPTION: Patients may be on chronic steroids (maximum dose 10 mg/day prednisone equivalent) if they are being given for disorders other than myeloma, i.e., adrenal insufficiency, rheumatoid arthritis, etc.
• Currently active, clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias or Class 3 or 4 congestive heart fail