Clinical trial NCT02943473 (phase 2, status: terminated)
Conditions: high risk smoldering multiple myeloma
ICD codes: G35, M15.3, M67.49, M89.09, M89.59, M94.29, Q78.6
Drugs: ibrutinib
SMILES: NC1=NC=NC2=C1C(=NN2[C@@H]1CCCN(C1)C(=O)C=C)C1=CC=C(OC2=CC=CC=C2)C=C1
Reason stopped: 
    poor accrual and risk/benefit ratio.
  
Eligibility criteria:

        Inclusion Criteria Disease Related

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

               1. Bone marrow plasma cells between 10% and 60%

               2. Serum M-protein ≥ 3 g/dL [except IgA ≥ 2 g/dL] or urine M-protein > 500 mg per 24
                  hours

               3. Serum free light chain ratio < 0.126 or > 8; an involved to uninvolved ratio of ≥
                  100 is permitted

               4. 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

          2. Diagnosed with SMM within the last 4 years

        Laboratory

          1. 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).

          2. 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)

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

             Demographic

          4. Men and women ≥ 18 years of age

          5. Eastern Cooperative Oncology Group (ECOG) performance status of < 2

        Exclusion Criteria Disease-Related

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

               1. Hypercalcemia: Serum calcium > 1 mg/dL above the upper limit of normal or > 11
                  mg/dL

               2. Renal insufficiency: Serum creatinine > 2 mg/dL or creatinine clearance < 30 mL
                  per min

               3. Anemia: Hemoglobin value > 2 g/dL below the upper limit of normal or a hemoglobin
                  value < 10 g/dL

               4. Bone lesions: One or more lytic lesions on skeletal radiography, CT, MRI, PET-CT,
                  or PET-MRI

          2. Bone marrow plasma cells < 10% or > 60%

          3. Has received prior anti-myeloma therapy of any type

          4. Has received prior bisphosphonate therapy

          5. 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

          6. Osteoporosis, defined as having a T-score on DEXA of ≤ -2.5

        Concurrent Conditions

          1. 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

          2. 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.

          3. Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug

          4. Recent infection requiring systemic treatment that was completed ≤ 14 days before the
             first dose of study drug

          5. Known bleeding disorders (eg, von Willebrand's disease) or hemophilia

          6. History of stroke or intracranial hemorrhage within 6 months prior to enrollment

          7. 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.

          8. Any uncontrolled active systemic infection

          9. Major surgery within 4 weeks of first dose of study drug

         10. 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