Ixazomib and Dexamethasone Versus Ixazomib, Dexamethasone and Lenalidomide, Randomized With NFKB2 Rearrangement

Inclusion Criteria

• •Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
• •Females of childbearing potential (FCBP)\* must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli-International Units (mIU)/mL within 10-14 days prior to and again within 24 hours of starting lenalidomide and ixazomib and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide through 90 days after the last dose of study drug; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy from the time of signing the informed consent form through 90 days after the last dose of study drug; in the event that the male patients choose to agree to practice true abstinence, this must follow the timelines detailed above; all patients assigned to the lenalidomide treatment group must be registered in and must comply with all requirements of the Revlimid Risk Evaluation and Mitigation Strategy (REMS) program
• •* \*A female of childbearing potential is a sexually mature woman who:
• •* 1\) has not undergone a hysterectomy or bilateral oophorectomy; or
• •* 2\) has not been naturally postmenopausal for at least 24 consecutive months
• •Multiple myeloma diagnosed according to standard criteria either currently or at the time of initial diagnosis
• •The patient has confirmed relapsed or refractory MM
• •For patients that relapse following a response to prior treatment with bortezomib or carfilzomib, six months must have elapsed since the last dose of treatment
• •The patient has received 1 to 3 prior lines of therapy. By definition, a single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy, bisphosphonate, or a single short course of steroids (ie, less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days) would not be considered prior lines of therapy
• •Patients must have measurable disease defined by at least 1 of the following measurements:
• •* Serum M-protein ≥ 1.0 g/dL (≥ 10 g/L) for an immunoglobulin (Ig)G myeloma, ≥ 0.1 g/dL for an immunoglobulin D (IgD) myeloma or 0.5 g/dL (≥ 5g/L) for an immunoglobulin A (IgA) myeloma
• •* Urine light chain ≥ 200 mg/24 hours
• •* Serum free light chain ≥ 10 mg/dL provided the free light chain (FLC) ratio is abnormal
• •* Patients with oligo- or non-secretory disease must have bone marrow involvement with at least 30% plasmacytosis on aspiration
• •Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2
• •Absolute neutrophil count (ANC) ≥ 1,000/mm³
• •Platelet count ≥ 75,000/mm³; in the case that platelets are between 50,000-75,000, the patient can be enrolled if the plasma cell count in the bone marrow is superior to ≥ 50%; to meet this hematological eligibility no transfusion support and hematological growth factor are not allowed within 7 days before study enrollment
• •Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN)
• •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN
• •Serum creatinine ≤ 2.5 mg/dL or a calculated creatinine clearance ≥ 50 mL/min