Venetoclax and Tocilizumab for the Treatment of Patients with Relapsed or Refractory t(11;14) Multiple Myeloma

Inclusion Criteria

• Subject must be >= 18 years of age
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of =< 2
• Diagnosis of multiple myeloma that requires treatment and has been previously treated with: * Has received at least 2 prior lines of therapy * Has had documented disease progression on or within 60 days after completion of the last therapy * Has received at least 2 consecutive cycles of lenalidomide and be relapsed/refractory to lenalidomide, as defined per protocol * Has received at least 2 consecutive cycles of a proteasome inhibitor (PI)
• Have MM positive for t(11;14) translocation as determined by an analytically validated fluorescence in-situ hybridization (FISH) assay per the central laboratory testing
• Subject must have had measurable disease at screening, defined as any of the following: * Serum monoclonal protein >= 1.0 g/dL (>= 10 g/L) by protein electrophoresis, or * >= 200 mg of monoclonal protein in the urine on 24-hour electrophoresis, or * Serum immunoglobulin free light chain (FLC) >= 10 mg/dL provided serum FLC ratio is abnormal
• Subjects with a history of autologous transplantation must have adequate peripheral blood counts as defined below, have recovered from any transplant related toxicity(s) and be > 100 days post-autologous transplant (prior to first dose of study drug)
• Absolute neutrophil count (ANC) >= 1000/uL (Subject may not use granulocyte colony-stimulating factor [G-CSF] within 1 week to achieve ANC eligibility criteria)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 1.5 x upper limit of normal range (ULN)
• Calculated creatinine clearance >= 30 mL/min using a modified Cockcroft- Gault calculation or a 24-hour urine collection for creatinine clearance
• Platelet count >= 75,000 cells/mm^3 and independent of transfusion for 2 weeks
• Hemoglobin >= 8.0 g/dL (Subjects may not receive blood transfusion within 1 week to achieve hemoglobin eligibility criteria)
• Total bilirubin =< 1.5 x ULN; Subjects with Gilbert's syndrome may have bilirubin > 1.5 x ULN
• If female, subject must be: * Postmenopausal defined as: ** Age > 55 years with no menses for 24 or more months without an alternative medical cause ** Age =< 55 years with no menses for 24 or more months without an alternative medical cause ** AND an follicle stimulating hormone (FSH) level > 40 IU/L OR * Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy) OR * A woman of childbearing potential (WOCP) practicing at least one protocol specified method of birth control starting at cycle 1 day 1 (or earlier) through at least 30 days after last dose of study drug
• Females of childbearing potential (must have negative results for pregnancy test performed: * At screening, on a serum or urine sample obtained within 28 days prior to the first study drug administration, * Prior to dosing, on a urine sample obtained on the first day of study drug dosing, if it has been > 7 days since obtaining the serum pregnancy test results * Females of non-childbearing potential (either postmenopausal or permanently surgically sterile as defined above) at screening do not require pregnancy testing
• Must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures

Exclusion Criteria

• Subject exhibits evidence of other clinically significant uncontrolled condition(s), including, but not limited to: * Acute infection within 14 days prior to first dose of study drug requiring antibiotic, antifungal, or antiviral therapy * Diagnosis of fever and neutropenia within 1 week prior to first dose of study drug
• Subject has a cardiovascular disability status of New York Heart Association class >= 3
• Subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular or hepatic disease within the last 6 months that, in the opinion of the investigator, would adversely affect his/her participation in the study
• Subject has a history of other active malignancies other than multiple myeloma within the past 3 years prior to study entry, with the following exceptions: * Adequately treated in situ carcinoma of the cervix uteri, * Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, * Localized prostate cancer Gleason grade 6 or lower AND with stable prostate specific antigen (PSA) levels off treatment * Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent
• Known human immunodeficiency viral (HIV) infection
• Active hepatitis B or C infection based on screening blood testing
• Subject is receiving other ongoing anti-myeloma therapy
• Subject has received any of the following within 7 days prior to the first dose of study drug: * Strong or moderate CYP3A inhibitors, or * Strong or moderate CYP3A inducers
• Subject has received any of the following within 14 days prior to the first dose of study drug or has not recovered to less than a grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy: any anti-myeloma therapy including chemotherapy, radiotherapy, or investigational therapy, including targeted small molecule agents
• Subject has received prior treatment with a BCL-2 family inhibitor
• Subject is pregnant, parturient, or breastfeeding; deprived of freedom by judicial or administrative decision; hospitalized and unable to provide consent, or otherwise unable to provide consent
• Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or star fruit within 3 days prior to the first dose of study drug
• Subject has received immunization with live vaccine within 60 days of dosing
• Recent corticosteroid therapy at a cumulative dose equivalent to > 140 mg of prednisone or a single dose equivalent to >= 40 mg of dexamethasone within 2 weeks prior to the first dose of study drug
• Subject’s decision to not divulge the race