Venetoclax and Dexamethasone in translocation (11;14) positive relapsed and refractory multiple myeloma (VICTORIA)

Prior treatment

• The use of live vaccines within 30 days before initiation of study treatment
• Autologous stem cell transplant within 12 weeks prior to initiation of study treatment
• Prior allogeneic stem cell transplantation with active graft-versus-host-disease

Other illness

• Any somatic or psychiatric condition that in the investigator’s opinion would impose excessive risk to the patient or would adversely affect the patient’s participation in this study
• Cardiovascular disability status of New York Heart Association Class greater than or equal to 3
• Severe ongoing infection that in the investigator’s opinion would impose excessive risk to the patient
• Known human immunodeficiency virus or active hepatitis B or C viral infection
• ≥ Grade 3 cardiac conduction system abnormalities unless patient has a pacemaker

Other

• Known intolerance to the study treatment
• Pregnant or breast-feeding females

• Male or female, age 18 years or older
• Female patients must agree to practice highly effective method of birth control until at least 30 days after the last dose of study treatment. Highly effective method of birth control is defined as the combination of both a hormonal and a barrier method of contraception
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent;
• Adequate organ function with the following laboratory results: o Absolute neutrophil count ≥ 1,000 cells/mm3 (1.0 x 109/L) o Platelet count ≥ 30,000 cells/ mm3 (30 x 109/L) (without transfusions required within 10 days prior to initiation of study treatment) o Hemoglobin ≥ 5 mmol/l; red blood cell transfusions and treatment with erythropoietin are permitted o Total Bilirubin ≤ 1.5 x upper limit of normal, except patients diagnosed with Gilbert’s syndrome that have been approved by the sponsor o Alanine transaminase ≤ 3.0 x upper limit of normal o Renal function: Estimated creatinine clearance by Cockcroft- Gault formula of ≥ 30 mL/min
• A prior diagnosis of multiple myeloma
• At least one prior line of therapy
• The presence of t(11;14) by fluorescent in situ hybridization
• Relapsed or refractory disease defined as o progressive disease  during treatment with the last line of therapy or  within 60 days after the last line of therapy or o minimal response or better not achieved after completion of at least two cycles of the last line of therapy
• Measurable disease defined as any of the following: o Serum monoclonal protein ≥ 10 g/L by serum protein electrophoresis o ≥ 200 mg of monoclonal protein in the urine on 24-hour electrophoresis o Serum free light chain ≥ 100 mg/L and abnormal serum kappa to lambda free light chain (FLC) ratio
• Life expectancy of ≥ 6 months
• ECOG performance status ≤ 2. (Patients with performance status > 2 based solely on bone pain secondary to multiple myeloma may be eligible following approval of the sponsor);
• A negative serum or urine pregnancy test if the subject is a female of childbearing potential, defined as any sexually mature female who: o has not undergone a hysterectomy or bilateral oophorectomy and o has not been naturally postmenopausal for at least 24 consecutive months  A sexually mature female who stopped having menstrual cycles due to cancer therapy cannot be considered naturally postmenopausal