Ixazomib Citrate in Treating Patients With Chronic Graft-versus-Host Disease
Condition: Chronic Graft Versus Host Disease
MeSH terms: Bronchiolitis Obliterans Syndrome; Graft vs Host Disease
Intervention: Ixazomib Citrate; Laboratory Biomarker Analysis; Quality-of-Life Assessment; Questionnaire Administration
Intervention description: Given PO; Correlative studies; Ancillary studies; Ancillary studies
Intervention MeSH terms: Ixazomib; Glycine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well ixazomib citrate works in treating patients with chronic
      graft-versus-host disease. Chronic graft-versus-host disease is a complication of a donor
      bone marrow or blood cell transplant, usually occurring more than three months after
      transplant, in which donor cells damage the host tissue. Ixazomib citrate may be an effective
      treatment for chronic graft-versus-host disease.
    

Eligibility criteria:

        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             be withdrawn by the patient at any time without prejudice to future medical care

          -  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 or exclusively non-heterosexual activity when
                  this is in line with the preferred and usual lifestyle of the subject; (periodic
                  abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and
                  withdrawal are not acceptable methods of contraception)

          -  Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree
             to one of the following:

               -  Agree to practice two effective contraception measures during the entire study
                  treatment period and through 90 days after the last dose of study drug, OR

               -  Agree to practice true abstinence or exclusively non-heterosexual activity when
                  this is in line with the preferred and usual lifestyle of the subject; (periodic
                  abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and
                  withdrawal are not acceptable methods of contraception)

          -  Patients must have a diagnosis of a chronic GVHD according to the National Institute
             of Health (NIH) Consensus Criteria

          -  Patients must have failed at least one prior line of systemic immune suppressive
             therapy for management of chronic GVHD

          -  Absolute neutrophil count (ANC) >= 1,000/mm^3

          -  Platelet count >= 75,000/mm^3; platelet transfusions are not allowed within 3 days
             before study enrollment

          -  Total bilirubin =< 1.5 x the upper limit of the normal range (ULN)

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN

          -  Calculated creatinine clearance >= 30 mL/min

        Exclusion Criteria:

          -  Female patients who are lactating or have a positive serum pregnancy test during the
             screening period

          -  Major surgery within 14 days before enrollment

               -  Does not include placement of venous access device, bone marrow biopsy, GVHD
                  diagnostic biopsy, or other routine procedures in chronic GVHD or
                  post-transplantation care

          -  Uncontrolled infection within 14 days before study enrollment

               -  Infection treated with appropriate antimicrobial therapy and without signs of
                  progression/treatment failure does not constitute an exclusion criterion

          -  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

               -  Chronic hypertension on medical therapy does not constitute an exclusion
                  criterion

          -  Systemic treatment, within 14 days before the first dose of ixazomib, with strong
             inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of
             cytochrome 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

          -  Active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV)
             positive

          -  Any serious medical or psychiatric illness that could, in the investigator's opinion,
             potentially interfere with the completion of treatment according to this protocol

          -  Known allergy to any of the study medications, their analogues, or excipients in the
             various formulations of any agent

          -  Non-hematologic malignancy within the past 2 years with the exception of:

               -  Adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid
                  cancer

               -  Carcinoma in situ of the cervix or breast

               -  Prostate cancer of Gleason grade 6 or less with stable prostate-specific antigen
                  levels

               -  Cancer considered cured by surgical resection or unlikely to impact survival
                  during the duration of the study

          -  Patient has >= grade 3 peripheral neuropathy, or grade 2 with pain on clinical
             examination during the screening period

          -  Treatment with non-Food and Drug Administration (FDA) approved drug within 21 days of
             start of this trial

          -  New systemic immune suppressive agent added for the treatment of chronic GVHD within 2
             weeks prior to enrollment

               -  Addition of a new systemic immune suppressive treatment simultaneously with
                  ixazomib is also prohibited

          -  Evidence of recurrent or progressive underlying malignant disease

          -  Karnofsky performance status < 70%

          -  Life expectancy less than 6 months