Carfilzomib 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: Carfilzomib; Laboratory Biomarker Analysis; Quality-of-Life Assessment; Questionnaire Administration
Intervention description: Given IV; Correlative studies; Ancillary studies; Ancillary studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This pilot phase II trial studies how well carfilzomib 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. Carfilzomib may be an effective
      treatment for chronic graft-versus-host disease.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of chronic GVHD according to National Institutes of Health (NIH) Consensus
             Criteria

               -  May have either classic chronic GVHD or overlap subtype of chronic GVHD

          -  Failure of at least one prior line of systemic immune suppressive therapy for
             management of chronic GVHD

          -  Subject underwent transplantation at least 3 months prior to enrollment

          -  Anticipated life expectancy >= 6 months

          -  Alanine aminotransferase (ALT) =< 3.5 times the upper limit of normal, unless due to
             chronic GVHD

          -  Bilirubin =< 2 mg/dL, unless due to chronic GVHD

          -  Absolute neutrophil count (ANC) >= 1.0 × 10^9/L

          -  Hemoglobin >= 8 g/dL

          -  Platelet count >= 50 × 10^9/L

          -  Creatinine clearance (CrCl) >= 15 mL/minute, either measured or calculated

          -  Signed informed consent in accordance with federal, local, and institutional
             guidelines

          -  Females of childbearing potential (FCBP) must agree to a pregnancy test at study
             enrollment and to practice contraception during the study

          -  Male subjects must agree to practice contraception during the study

        Exclusion Criteria:

          -  Evidence of recurrent or progressive underlying malignant disease

          -  Pregnant or lactating females

          -  Surgery within 21 days prior to 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 prior to enrollment

               -  Infection treated with appropriate antimicrobial therapy and without signs of
                  progression/treatment failure does not constitute an exclusion criterion

          -  Documented human immunodeficiency virus (HIV) infection

          -  Active hepatitis B or C infection

          -  Documented unstable angina or myocardial infarction within 6 months prior to
             enrollment, New York Heart Association (NYHA) class III or IV heart failure,
             uncontrolled angina, severe uncontrolled ventricular arrhythmias, sick sinus syndrome,
             or electrocardiographic evidence of acute ischemia or grade 3 conduction system
             abnormalities (unless subject has a pacemaker), left ventricular ejection fraction
             (LVEF) < 40%, history of torsade de pointe

          -  Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment

               -  Sustained systolic blood pressure > 160 or diastolic blood pressure > 100 despite
                  medical therapy; sustained blood sugar > 300 despite medical therapy

               -  Chronic hypertension or diabetes on appropriate medical therapy does not
                  constitute an exclusion criterion

          -  Non-hematologic malignancy within the past 3 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

          -  Significant neuropathy per Common Terminology Criteria for Adverse Events (CTCAE)
             version (ver.) 4.03 or current version (grade 3 and above, or grade 2 with pain)
             within 14 days prior to enrollment

          -  History of allergy to Captisol (a cyclodextrin derivative used to solubilize
             carfilzomib)

          -  Contraindication to all available herpes simplex virus (HSV)/varicella prophylactic
             antiviral drugs

          -  Pleural effusions requiring thoracentesis, or ascites requiring paracentesis, within
             14 days prior to enrollment

          -  Any other clinically significant medical or psychological disease or condition that,
             in the investigator's opinion, may interfere with protocol adherence or a subject's
             ability to give informed consent

          -  New systemic immune suppressive agent added for the treatment of chronic GVHD within 2
             weeks prior to enrollment

          -  Treatment with a non-Food and Drug Administration (FDA) approved drug in the previous
             4 weeks