Phase II Study of IRD (Ixazomib, Lenalidomide, Dexamethasone) Post Autologous Stem Cell Transplantation Followed by Maintenance Ixazomib or Lenalidomide for Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Ixazomib; Lenalidomide; Dexamethasone
Intervention MeSH terms: Dexamethasone; Dexamethasone acetate; Lenalidomide; Ixazomib; BB 1101
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 236.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Multiple Myeloma; Autologous Stem Cell Transplantation; Ixazomib; Lenalidomide; Dexamethasone

Summary:

      The purpose of this research study is to evaluate a treatment regimen called IRD which will
      be given to participants after their stem cell transplant in an effort to help prolong the
      amount of time the participants are disease-free after transplant. IRD is a three-drug
      regimen consisting of ixazomib, lenalidomide (also called Revlimid), and dexamethasone. After
      4 cycles of IRD, the participants will be randomized to receive maintenance therapy either
      with ixazomib or lenalidomide.
    

Eligibility criteria:

        Inclusion Criteria

        Each patient must meet all of the following inclusion criteria to begin IRD Consolidation:

          -  Between the ages of 18 and 70 years of age (inclusive) at time of enrollment

          -  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             be withdrawn by the patient at any time without prejudice to future medical care

          -  Confirmed diagnosis of symptomatic multiple myeloma. (Patients with multiple myeloma
             with secondary amyloidosis are eligible.)

          -  Received at least two cycles of any regimen as initial systemic therapy for multiple
             myeloma and are within 2-16 months of the first dose of initial therapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance
             status 0, 1, or 2

          -  Adequate organ function as defined below:

        Absolute neutrophil count (ANC) >= 1,000 mm^3 Platelet count >= 75,000/mm^3; platelet
        transfusions to help patient meet eligibility criteria are not allowed within 7 days before
        study enrollment Total bilirubin <= 1.5 x upper limit of normal range (ULN) Alanine
        aminotransferase (ALT) and aspartate aminotransferase (AST) <=3 x ULN Calculated creatinine
        clearance >= 30 mL/min

          -  Women of childbearing potential must follow pregnancy testing requirements as outlined
             in the Revlimid REMS program material. This is defined as either committing to
             continued abstinence from heterosexual intercourse or beginning TWO acceptable methods
             of contraception (one highly effective method and one additional effective method AT
             THE SAME TIME) at least 28 days prior to the start of lenalidomide, for the duration
             of study participation, and for 28 days following the last dose of lenalidomide. Women
             of childbearing potential must also agree to ongoing pregnancy testing.

          -  Men must agree to use a latex condom during sexual contact with a woman of
             childbearing potential even if they have had a successful vasectomy. All patients must
             be counseled at a minimum of every 28 days about pregnancy precautions and risks of
             fetal exposure. Should a woman become pregnant or suspect she is pregnant while
             participating in this study, she must inform her treating physician immediately.

          -  All study participants must be registered into the mandatory Revlimind REMS program
             and be willing to comply with its requirements. Per standard Revlimid REMS program
             requirements, all physicians who prescribe lenalidomide for research subjects enrolled
             into this trial, must be registered in, and must comply with, all requirements of the
             Revlimid REMS program.

        Exclusion Criteria

        Patients meeting any of the following exclusion criteria are not to be enrolled in the
        study:

          -  Female patients who are lactating or have a positive serum pregnancy test during the
             screening period

          -  Evidence of MM disease progression any time prior to enrollment. Progression from
             smoldering/asymptomatic MM to symptomatic MM is not exclusionary.

          -  Tandem autologous transplantation

          -  History of plasma cell leukemia or MM CNS involvement

          -  Administration or planned administration of any other concomitant chemotherapy,
             immunotherapy, radiotherapy, or any ancillary therapy which would be considered a
             treatment of multiple myeloma until Day +28 post-transplant through discontinuation
             from study. Patients may be on corticosteroids if they are being given for disorders
             other than multiple myeloma (e.g., adrenal insufficiency, rheumatoid arthritis, etc.)

          -  Any serious medical or psychiatric illness that could, in the investigator's opinion,
             potentially interfere with the completion of treatment according to this protocol.

          -  Prior organ transplant requiring immunosuppressive therapy

          -  Active hepatitis A, B or C virus infection, or known human immunodeficiency virus
             (HIV) positive

          -  Known allergy to any of the study medications, their analogues, or excipients in the
             various formulations of any agent

          -  Known GI disease or GI procedure that could interfere with the oral absorption or
             tolerance of ixazomib

          -  Concurrent hematologic or non-hematologic malignancy requiring treatment (other than
             multiple myeloma and secondary amyloidosis)

          -  Cardiac syncope, uncompensated NYHA Class 3 or 4 congestive heart failure, myocardial
             infarction within the previous six months, unstable angina pectoris, clinically
             significant repetitive ventricular arrhythmias despite antiarrhythmic treatment,
             severe orthostatic hypotension, or clinically important autonomic disease

          -  Grade >= 3 peripheral neuropathy, or Grade 2 with pain on clinical examination during
             the screening period

          -  Major surgery within 14 days prior to enrollment

          -  Infection requiring systemic antibiotic therapy or other serious infection within 14
             days prior to enrollment

          -  Participation in other clinical trials, including those with other investigational
             agents not included in this trial, within 30 days prior to enrollment and throughout
             the duration of this trial