Shorter Course Tacro After NMA, Related Donor PBSCT With High-dose Posttransplant Cy for Hard-to-Engraft Malignancies
Condition: Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Small Lymphocytic Lymphoma; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Chronic Myeloid Leukemia; Chronic Myeloproliferative Disorders; Multiple Myeloma; Plasma Cell Neoplasm; Plasma Cell Dyscrasia; Myelofibrosis; Polycythemia Vera; Essential Thrombocythemia; Plasma Cell Leukemia
MeSH terms: Leukemia; Multiple Myeloma; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Polycythemia Vera; Neoplasms, Plasma Cell; Plasmacytoma; Leukemia, Prolymphocytic; Leukemia, Plasma Cell; Myelodysplastic Syndromes; Polycythemia; Thrombocytosis; Thrombocythemia, Essential; Myeloproliferative Disorders; Paraproteinemias
Intervention: Fludarabine; Cyclophosphamide; Total body irradiation; Tacrolimus; Mycophenolate mofetil
Intervention description: Days -6 through -2: 30 mg/m^2 IV daily; Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily; Day -1: 200 cGy in a single fraction; Start on Day 5 through either Day 60 or Day 90 depending on cohort assignment. May be continued through Day 180 depending on GVHD status.; Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Intervention MeSH terms: Mycophenolic Acid; Cyclophosphamide; Fludarabine; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 117.0
Sex: All
Healthy volunteers: No
Keywords: immunosuppression; nonmyeloablative; non-myeloablative; allogeneic; tacrolimus; peripheral blood; cyclophosphamide; mycophenolate mofetil

Summary:

      To see if it is possible to use short-duration tacrolimus after a peripheral blood stem cell
      transplant in certain malignancies that are considered difficult to engraft.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Presence of a suitable related HLA-haploidentical or -matched stem cell donor, or a
             10/10 matched unrelated donor

          -  Eligible diagnoses: myelodysplastic syndrome (MDS) with at least 1 poor-risk feature;
             small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL) with 17p
             deletion or with progression < 6 months after a second or greater treatment regimen;
             T-cell prolymphocytic leukemia (PLL) in partial response or better; interferon- or
             tyrosine-kinase-refractory chronic myeloid leukemia (CML), or CML in second or
             subsequent chronic phase; Philadelphia chromosome negative (Ph-) myeloproliferative
             disease, including myelofibrosis; Multiple myeloma or plasma cell leukemia in partial
             response or better; Hematologic malignancy in complete remission with minimal residual
             disease (MRD) detectable by conventional cytogenetics, FISH, flow cytometry, or
             molecular testing

          -  Any previous autologous transplant must have occurred > 3 months ago

          -  Left ventricular ejection fraction (LVEF) >= 35%, or shortening fraction > 25%

          -  Bilirubin <= 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis)

          -  AST and ALT <= 5 x institutional upper limit of normal

          -  FEV1 and FVC >= 40% of predicted; if unable to perform pulmonary function testing,
             oxygen saturation > 92% on room air

          -  ECOG performance status <= 2, or Karnofsky/Lansky status >= 60

        Exclusion Criteria:

          -  Pregnancy or active breastfeeding

          -  Uncontrolled active infection

          -  Previous allogeneic transplant

          -  Active extramedullary leukemia or active central nervous system (CNS) malignant
             disease