Study on the Effect of Ibrutinib on High Risk Smoldering Multiple Myeloma Patients

Inclusion Criteria Disease Related

High risk SMM, defined as follows by Mayo Clinic criteria:

Bone marrow plasma cells between 10% and 60%
Serum M-protein ≥ 3 g/dL [except IgA ≥ 2 g/dL] or urine M-protein > 500 mg per 24 hours
Serum free light chain ratio < 0.126 or > 8; an involved to uninvolved ratio of ≥ 100 is permitted
Measurable disease, defined as: M-protein ≥ 1 g/dL OR Bence-Jones protein (BJP) > 200 mg/24 hr OR involved free light chain > 100 mg/dL
Diagnosed with SMM within the last 4 years

Laboratory

Adequate hematologic function independent of transfusion and growth factor support for at least 7 days prior to screening, with the exception of pegylated G-CSF (pegfilgrastim) and darbopoetin which require at least 14 days prior to screening defined as:

Absolute neutrophil count > 750 cells/mm3 (1.0 x 109/L).
Platelet count > 75,000 cells/mm3 (75 x 109/L).

Adequate hepatic and renal function defined as:

Serum aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x upper limit of normal (ULN).
Estimated creatinine clearance ≥ 30 ml/min (Cockcroft-Gault)
Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin, in which case the total bilirubin should be < 3 x ULN)

PT/INR < 1.5 x ULN and PTT (aPTT) < 1.5 x ULN

Demographic

Men and women ≥ 18 years of age
Eastern Cooperative Oncology Group (ECOG) performance status of < 2

Exclusion Criteria Disease-Related

No end organ damage attributable to a plasma cell disorder, defined as having ANY of the following:

Hypercalcemia: Serum calcium > 1 mg/dL above the upper limit of normal or > 11 mg/dL
Renal insufficiency: Serum creatinine > 2 mg/dL or creatinine clearance < 30 mL per min
Anemia: Hemoglobin value > 2 g/dL below the upper limit of normal or a hemoglobin value < 10 g/dL
Bone lesions: One or more lytic lesions on skeletal radiography, CT, MRI, PET-CT, or PET-MRI
Bone marrow plasma cells < 10% or > 60%
Has received prior anti-myeloma therapy of any type
Has received prior bisphosphonate therapy
Has received an investigational drug, investigational vaccine, or has used an investigational medical device within 4 weeks or 4 half-lives, whichever is longer, before Cycle 1, Day 1 of study therapy
Osteoporosis, defined as having a T-score on DEXA of ≤ -2.5

Concurrent Conditions

History of other malignancies, except:

Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician
Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
Adequately treated carcinoma in situ without evidence of disease
Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc). Any use of corticosteroids EITHER for > 14 days OR at dosages > 20 mg/day of prednisone or equivalent is prohibited.
Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug
Recent infection requiring systemic treatment that was completed ≤ 14 days before the first dose of study drug
Known bleeding disorders (eg, von Willebrand's disease) or hemophilia
History of stroke or intracranial hemorrhage within 6 months prior to enrollment
Known HIV, HCV or HBV infection. Subjects who are positive for hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.
Any uncontrolled active systemic infection
Major surgery within 4 weeks of first dose of study drug
Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigators' opinion, could compromise the subject's safety or put the study outcomes at undue risk