Ixazomib Citrate, Pomalidomide, Dexamethasone, Stem Cell Transplant in Treating Relapsed or Refractory Multiple Myeloma
Condition: Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Autologous Hematopoietic Stem Cell Transplantation; Dexamethasone; Ixazomib Citrate; Laboratory Biomarker Analysis; Pomalidomide
Intervention description: Undergo ASCT; Given PO; Given PO; Correlative studies; Given PO
Intervention MeSH terms: Dexamethasone; Dexamethasone acetate; Pomalidomide; Ixazomib; Ichthammol; BB 1101; Glycine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well ixazomib citrate, pomalidomide, dexamethasone, and stem
      cell transplantation works in treating patients with multiple myeloma that has come back or
      does not respond to treatment. Giving chemotherapy, such as pomalidomide and dexamethasone,
      before a stem cell transplant helps kill any cancer cells that are in the body and helps make
      room in the patient?s bone marrow for new blood-forming cells (stem cells) to grow. After
      treatment, stem cells are collected from the patient's blood and stored. More chemotherapy is
      then given to prepare the bone marrow for the stem cell transplant. The stem cells are then
      returned to the patient to replace the blood-forming cells that were destroyed by the
      chemotherapy. Giving ixazomib citrate in addition to pomalidomide, dexamethasone, and stem
      cell transplantation may work better in treating patients with relapsed or refractory
      multiple myeloma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Previously treated ASCT naive MM patients, currently with relapsed or refractory
             disease who are being considered for single ASCT for relapsed disease; patients must
             be eligible to undergo a stem cell transplant as per institutional criteria for
             selection at the time of registration

          -  Calculated creatinine clearance (using Cockcroft-Gault equation) >= 30 mL/min

          -  Absolute neutrophil count (ANC) >= 1000/mm^3

          -  Platelet count >= 75 x 10^9/L unless the participant has >= 50% bone marrow
             infiltration in which case a platelet count of >= 50 x 10^9/L is allowed

          -  Hemoglobin >= 9.0 g/dL

          -  Total bilirubin =< 1.5 x the upper limit of the normal range (ULN) or if total
             bilirubin is > 1.5 x ULN, the direct bilirubin must be =< 2.0 mg/dL

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN or < 5
             x ULN if liver involvement

          -  Patients with measurable disease defined as at least one of the following:

               -  Serum monoclonal protein >= 1.0 g/dL by protein electrophoresis

               -  >= 200 mg of monoclonal protein in the urine on 24-hour electrophoresis

               -  Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum
                  immunoglobulin kappa to lambda free light chain ratio

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

          -  Willing to provide informed written consent

          -  Negative pregnancy test done =< 7 days prior to registration, for persons of
             childbearing potential only

          -  Willing to follow strict birth control measures

          -  Persons of childbearing potential, agree to one of the following:

               -  Practice 2 effective methods of contraception, at the same time, from the time of
                  signing the informed consent form through 90 days after the last dose of study
                  drug, AND must also adhere to the guidelines of any treatment-specific pregnancy
                  prevention program, if applicable, OR

               -  Agree to practice true abstinence when this is in line with the preferred and
                  usual lifestyle of the subject; (Periodic abstinence [e.g., calendar, ovulation,
                  symptothermal, post-ovulation methods] and withdrawal are not acceptable methods
                  of contraception)

          -  Persons able to father a child: even if surgically sterilized (i.e., status
             post-vasectomy), must agree to one of the following:

               -  Agree to practice effective barrier contraception during the entire study
                  treatment period and through 90 days after the last dose of study drug, OR

               -  Must also adhere to the guidelines of any treatment-specific pregnancy prevention
                  program, if applicable, OR

               -  Agree to practice true abstinence when this is in line with the preferred and
                  usual lifestyle of the subject; (Periodic abstinence [e.g., calendar, ovulation,
                  symptothermal, post-ovulation methods] and withdrawal are not acceptable methods
                  of contraception)

          -  Willing to follow the requirements of the Pomalyst REMS program

          -  Willing to return to return to enrolling institution for follow-up (during the Active
             Monitoring Phase of the study)

          -  Willing to provide bone marrow samples under Institutional Review Board (IRB)#521-93
             for correlative research purposes

        Exclusion Criteria:

          -  Diagnosed or treated for another malignancy =< 2 years prior to registration or
             previously diagnosed with another malignancy and have any evidence of residual disease

               -  NOTE: If there is a history or prior malignancy, patient must not be receiving
                  other specific treatment for their cancer; patients with non-melanoma skin cancer
                  or carcinoma in situ of any type, or low-risk prostate cancer after curative
                  therapy, are not excluded if they have undergone complete resection

               -  NOTE: Platelet transfusions to help patients meet eligibility criteria are not
                  allowed =< 3 days prior to study registration

          -  Any of the following:

               -  Pregnant persons

               -  Nursing persons

               -  Persons of childbearing potential who are unwilling to employ adequate
                  contraception

          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens; NOTE: this includes uncompensated heart or lung disease

          -  Receiving any other investigational agent which would be considered as a treatment for
             the primary neoplasm; NOTE: Bisphosphonates are considered to be supportive care
             rather than therapy and are allowed while on protocol treatment

          -  Patient has >= grade 2 peripheral neuropathy, or grade 1 with pain on clinical
             examination during the screening period

          -  Major surgery =<14 days prior to registration

          -  Systemic treatment with strong CYP3A inducers (rifampin, rifapentine, rifabutin,
             carbamazepine, phenytoin, phenobarbital) or use of Ginkgo biloba or St. John?s wort =<
             14 days prior to registration

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements. NOTE: Any electrocardiogram (ECG) abnormality at screening must be
             documented by the investigator as not medically relevant

          -  Corrected QT (QTc) > 470 milliseconds (msec) on a 12-lead ECG obtained during the
             screening period; Note: If a machine reading is above this value, the ECG should be
             reviewed by a qualified reader and confirmed on a subsequent ECG

          -  Known human immunodeficiency virus (HIV) positive

          -  Known hepatitis B surface antigen-positive status, or known or suspected active
             hepatitis C infection

          -  Known allergy to any of the study medications, their analogues or excipients in the
             various formulations

          -  Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral
             absorption or tolerance of study treatment including difficulty swallowing

          -  Diarrhea > grade 1, based on the National Cancer Institute (NCI) Common Terminology
             Criteria for Adverse Events (CTCAE) version (v) 4.0 grading, in the absence of
             antidiarrheals

          -  Failure to have fully recovered (i.e., =< grade 1 toxicity) from the reversible
             effects of prior chemotherapy

          -  Radiotherapy =< 14 days prior to registration; NOTE: If the involved field is small, 7
             days will be considered a sufficient interval between treatment and administration of
             the ixazomib

          -  Central nervous system involvement with disease under study (myeloma), or concurrent
             AL amyloidosis or plasma cell leukemia

          -  Patients that have previously been treated with ixazomib, or participated in a study
             with ixazomib whether treated with ixazomib or not

          -  Prior stem cell transplantation for myeloma