Pembrolizumab, Ixazomib Citrate, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma
Condition: Recurrent Plasma Cell Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Dexamethasone; Ixazomib Citrate; Laboratory Biomarker Analysis; Pembrolizumab
Intervention description: Given PO; Given PO; Correlative studies; Given IV
Intervention MeSH terms: Dexamethasone; Dexamethasone acetate; Pembrolizumab; Ixazomib; Ichthammol; BB 1101; Glycine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well pembrolizumab works when given together with ixazomib
      citrate and dexamethasone in treating patients with multiple myeloma that has come back
      (relapsed). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the
      body's immune system attack the cancer, and may interfere with the ability of tumor cells to
      grow and spread. Ixazomib citrate may stop the growth of tumor cells by blocking some of the
      enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, work in
      different ways to stop the growth of cancer cells, either by killing the cells, by stopping
      them from dividing, or by stopping them from spreading. Giving pembrolizumab together with
      ixazomib citrate and dexamethasone may work better in treating patients with multiple
      myeloma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of relapsed, symptomatic multiple myeloma by International Myeloma Working
             Group (IMWG) diagnostic criteria for multiple myeloma

          -  Age >= 18 years

          -  Calculated creatinine clearance (using Cockcroft-Gault equation below) >= 30 mL/min
             (obtained =< 14 days prior to registration)

          -  Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 14 days prior to
             registration)

          -  Platelet count >= 75000/mm^3; Note: Platelet transfusion is not allowed =< 3 days
             prior to registration (obtained =< 14 days prior to registration)

          -  Hemoglobin >= 8.0 g/dL (obtained =< 14 days prior to registration)

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 14 days prior to
             registration)

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN
             (obtained =< 14 days prior to registration)

          -  Must have relapsed or refractory disease after treatments including three therapies:
             proteasome inhibitors, immunomodulatory imide drugs (IMiDs), and anti-CD38 antibody

          -  Measurable disease of multiple myeloma as defined by at least ONE of the following:

               -  Serum monoclonal protein >= 1.0 g/dL

               -  >= 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, or 1

          -  Provide informed written consent

          -  Negative pregnancy test done =< 7 days prior to registration, for women of
             childbearing potential only

          -  Willing to follow strict birth control measures;

               -  Female patients: If they are 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 120 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)

               -  Male patients: 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 120 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 return to enrolling institution for follow-up (during the Active Monitoring
             Phase of the study)

          -  Willing to provide bone marrow and blood samples for planned research

        Exclusion Criteria:

          -  Myeloma disease that is refractory to ixazomib treatment

          -  Has a known additional malignancy that is progressing or requires active treatment;
             exceptions include early stage cancers (carcinoma in situ or stage 1) treated with
             curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the
             skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially
             curative therapy

          -  Any of the following:

               -  Pregnant women

               -  Nursing women

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception

          -  Other co-morbidity which would interfere with patient's ability to participate in
             trial, e.g. uncontrolled infection, uncompensated heart or lung disease

          -  Other concurrent chemotherapy, or any ancillary therapy considered investigational =<
             14 days prior to study registration; NOTE: Bisphosphonates are considered to be
             supportive care rather than therapy, and are thus allowed while on protocol treatment

          -  Peripheral neuropathy >= grade 3 on clinical examination or grade 2 with pain during
             the screening period

          -  Major surgery =< 14 days prior to study registration

          -  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
             study drugs

          -  Participation in any other clinical trials with other investigational agents not
             included in this trial =< 21 days prior to registration

          -  Has active autoimmune disease that has required systemic treatment =< 2 years prior to
             study registration (i.e. with use of disease modifying agents, corticosteroids or
             immunosuppressive drugs);

               -  NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic
                  corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.)
                  is not considered a form of systemic treatment

          -  Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis

          -  Has a known history of interstitial lung disease

          -  Has an active infection requiring systemic therapy

          -  Has a history of current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent

          -  Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

          -  Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or
             hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is
             detected)

          -  Has a known history of active TB (Bacillus tuberculosis)

          -  Has received a live vaccine =< 30 days prior to study registration

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis

          -  Allogeneic hematopoietic stem cell transplant

          -  Systemic treatment with strong CYP3A inducers (rifampin, rifapentine, rifabutin,
             carbamazepine, phenytoin, phenobarbital), or use of St. John's wort =< 14 days prior
             to registration

          -  Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral
             absorption or tolerance of ixazomib including difficulty swallowing