Tacrolimus, Bortezomib, & Thymoglobulin in Preventing Low Toxicity GVHD in Donor Blood Stem Cell Transplant Patients
Condition: Acute Leukemia; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Diffuse Large B-Cell Lymphoma; Follicular Lymphoma; Graft Versus Host Disease; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Myelodysplastic Syndrome; Myelofibrosis; Myeloproliferative Neoplasm; Small Lymphocytic Lymphoma
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myelodysplastic Syndromes; Myeloproliferative Disorders; Graft vs Host Disease
Intervention: Thymoglobulin; Bortezomib; Tacrolimus
Intervention description: Given IV; Given IV; Given IV and PO
Intervention MeSH terms: Bortezomib; Tacrolimus; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well tacrolimus, bortezomib, and anti-thymocyte globulin
      (thymoglobulin) work in preventing low toxicity graft versus host disease (GVHD) in patients
      with blood cancer who are undergoing donor stem cell transplant. Tacrolimus and
      anti-thymocyte globulin may reduce the risk of the recipient's body rejecting the transplant
      by suppressing the recipient's immune system. Giving bortezomib after the transplant may help
      prevent GVHD by stopping the donor's cells from attacking the recipient. Giving tacrolimus,
      bortezomib, and anti-thymocyte globulin may be a better way to prevent low toxicity GVHD in
      patients with blood cancer undergoing donor stem cell transplant.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with acute leukemia, chronic myelogenous leukemia, myeloproliferative
             disorder and myelodysplasia with no circulating blasts and with less than 5% blasts in
             the bone marrow within 4 weeks of the start of transplant conditioning regimen

          -  Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma; follicular,
             marginal zone, diffuse large B-cell or mantle cell lymphoma with chemo-sensitive
             disease at time of transplant

          -  Patients must have a related or unrelated peripheral blood stem cell donor; sibling
             donor must be a 6/6 match for human leukocyte antigen (HLA)-A and -B at intermediate
             (or higher) resolution, and -DRB1 at high resolution using deoxyribonucleic acid
             (DNA)-based typing, and must be willing to donate peripheral blood stem cells and meet
             institutional criteria for donation; unrelated donor must be 8/8 match at HLA-A, -B,
             -C and -DRB1 at high resolution using DNA-based typing; unrelated donor must be
             willing to donate peripheral blood stem cells and be medically eligible to donate stem
             cells according to National Marrow Donor Program (NMDP) criteria

          -  Cardiac function: ejection fraction > 40%

          -  Estimated creatinine clearance greater than 50 mL/minute (using the Cockcroft-Gault
             formula and actual body weight)

          -  Pulmonary function: carbon monoxide diffusing capability test (DLCO) ≥ 40% (adjusted
             for hemoglobin) and forced expiratory volume in 1 second (FEV1) ≥ 50%

          -  Total bilirubin < 1.5 x the upper limit of normal; patients who have been diagnosed
             with Gilbert's disease are allowed to exceed the defined bilirubin value of 1.5 x the
             upper limit of normal

          -  Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 2.5 x the upper
             normal limit

          -  Female subjects (unless postmenopausal for at least 1 year before the screening visit,
             or surgically sterilized), agree to practice two effective methods of contraception or
             agree to completely abstain from heterosexual intercourse from the time of signing the
             informed consent through 12 months post-transplant

          -  Male subjects (even if surgically sterilized), of partners of women of childbearing
             potential must agree to practice effective barrier contraception or abstain from
             heterosexual intercourse from the time of signing the informed consent through 12
             months post-transplant

          -  Signed informed consent

        Exclusion Criteria:

          -  Prior allogeneic transplant

          -  Karnofsky performance score < 70%

          -  Active central nervous system (CNS) involvement by malignant cells

          -  Patients with uncontrolled bacterial, viral, or fungal infections (currently taking
             medication and with progression or no clinical improvement) at time of enrollment

          -  Patients with transformed lymphoma (e.g., Richter's transformation arising in
             follicular lymphoma or chronic lymphocytic leukemia)

          -  Patients seropositive for the human immunodeficiency virus (HIV)

          -  Patient with active hepatitis B or C

          -  Patients with hypersensitivity to bortezomib, boron, or mannitol

          -  Patients with > grade 2 sensory peripheral neuropathy

          -  Myocardial infarction within 6 months prior to enrollment or New York Heart
             Association (NYHA) class III or IV heart failure, uncontrolled angina, severe
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities; prior to study entry, any
             electrocardiography (ECG) abnormality at screening must be documented by the
             investigator as not medically relevant

          -  Female patients who are lactating or pregnant

          -  Patients with a serious medical or psychiatric illness likely to interfere with
             participation in this clinical study

          -  Patients with prior malignancies, except resected basal cell carcinoma or treated
             cervical carcinoma in situ; cancer treated with curative intent > 5 years previously
             will be allowed; cancer treated with curative intent < 5 years previously will not be
             allowed unless approved by the protocol officer or one of the protocol chairs