Study of Ixazomib to Prevent Recurrent or Late Acute and Chronic Graft-versus-Host Disease 1-year After Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Hematologic Malignancies
Condition: Myeloid Hematologic Malignancy; Lymphoid Hematologic Malignancy
MeSH terms: Neoplasms; Hematologic Neoplasms; Bronchiolitis Obliterans Syndrome; Graft vs Host Disease
Intervention: Ixazomib
Intervention description: Ixazomib beginning between day +100 to +150 at a dose of 4 mg orally once per week (3 weeks on/ 1 week off).
Intervention MeSH terms: Ixazomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: This is a single arm phase 2 study to evaluate a post-transplant proteasome inhibitor, ixazomib, as prophylaxis against recurrent or late acute and chronic GVHD. Ixazomib will be initiated within days 100 to 150 post-transplant in patient's ≥ 18 years-old with either myeloid or lymphoid hematologic malignancy treated with a RI or NMA HSCT and will have received calcineurin inhibitor based drug (tacrolimus or cyclosporin) and methotrexate as part of their initial GVHD prophylaxis.
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Ixazomib; Graft-versus-Host Disease; Allogeneic Hematopoietic Stem Cell Transplantation; 16-076

Summary:

      This is a single arm open label phase 2 study evaluating the potential effect of ixazomib on
      the prevention of recurrent or late acute graft-versus-host disease (GVHD) and chronic GVHD
      at 1-year following reduced intensity (RI) or non-myeloablative (NMA) allogeneic
      hematopoietic stem cell transplantation (HSCT) for the treatment of hematologic malignancies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients 18 years or older.

          -  Diagnosis: myeloid or lymphoid hematologic malignancy treated with a RI or NMA
             conditioning HSCT who received calcineurin inhibitor based drug (for example:
             tacrolimus or cyclosporin) and methotrexate as part of their initial GVHD prophylaxis.
             Patients who received sirolimus as part of their GVHD prophylaxis will be eligible.

          -  Recipients of 8-7/8 HLA-matched donor. Post-HSCT period within day +100 to day +150.

          -  Female patients who:

               -  Are postmenopausal for at least 1 year before the screening visit, OR

               -  Are surgically sterile, OR

               -  If they are of childbearing potential, agree to 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, OR

               -  Agree to practice true abstinence when this is in line with the preferred and
                  usual lifestyle of the subject (periodic abstinence 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 90 days after the last dose of study drug, OR

               -  Agree to practice true abstinence when this is in line with the preferred and
                  usual lifestyle of the subject (periodic abstinence and withdrawal are not
                  acceptable methods of contraception).

          -  Organ Function and Performance Status Criteria:

          -  Karnofsky score ≥ 70 %

          -  Absolute neutrophil count (ANC) ≥ 1000/mm3 and platelet count ≥ 75,000/mm3. Platelet
             transfusions to help patients meet eligibility criteria are not allowed within 3 days
             before study enrollment.

          -  Calculated creatinine clearance ≥ 30 mL/min (based on the Cockcroft and Gault method)

          -  Total bilirubin ≤ 1.5 x upper limit of normal range (ULN).

          -  AST/ALT ≤ 3 x ULN (unless benign congenital hyperbilirubinemia).

          -  Hemoglobin > 8.0 g/dL. Red blood cell transfusions to help patients meet eligibility
             criteria are not allowed within 3 days before study enrollment.

        Exclusion Criteria:

          -  Disease: evidence of progressive disease at the time of study enrollment.

          -  Prior Therapy: one or more prior allogeneic stem cell transplantation (prior
             autologous transplant is acceptable).

          -  Active acute or chronic GVHD.

          -  Active and uncontrolled infection.

          -  Pregnant or breast feeding.

          -  Major surgery within 14 days before enrollment.

          -  Evidence of current uncontrolled cardiovascular conditions, including uncontrolled
             hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure,
             unstable angina, or myocardial infarction within the past 6 months.

          -  Systemic treatment, within 14 days before the first dose of ixazomib, with strong
             inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of
             CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole,
             nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin,
             carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort.

          -  Any serious medical or psychiatric illness that could, in the investigator's opinion,
             potentially interfere with the completion of treatment according to this protocol.

          -  Patient or guardian unable to give informed consent or unable to comply with the
             treatment protocol including appropriate supportive care, follow-up and research
             tests.

          -  Patients with known allergy to boron or boron-containing products, 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 including difficulty swallowing.

          -  Diagnosed or treated for another malignancy within 2 years before study enrollment or
             previously diagnosed with another malignancy and have any evidence of residual
             disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are
             not excluded if they have undergone complete resection.

          -  Patient with ≥ Grade 3 peripheral neuropathy, or Grade 2 with pain on clinical
             examination during the screening period.

          -  Received post-transplant cyclophosphamide