Fludarabine Phosphate and Total Body Irradiation Followed by a Donor Peripheral Stem Cell Transplant in Treating Patients With Myelodysplastic Syndromes or Myeloproliferative Disorders
Condition: Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Essential Thrombocythemia; Myeloproliferative Neoplasm; Paroxysmal Nocturnal Hemoglobinuria; Polycythemia Vera; Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase; Primary Myelofibrosis; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts
MeSH terms: Leukemia; Preleukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Polycythemia Vera; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Hemoglobinuria; Anemia; Myelodysplastic Syndromes; Primary Myelofibrosis; Myeloproliferative Disorders; Polycythemia; Thrombocytosis; Thrombocythemia, Essential; Anemia, Refractory; Hemoglobinuria, Paroxysmal; Anemia, Refractory, with Excess of Blasts; Leukopenia; Thrombocytopenia; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      This phase II trial studies the side effects and best dose of total-body irradiation when
      given together with fludarabine phosphate followed by a donor peripheral stem cell transplant
      in treating patients with myelodysplastic syndromes (MDS) or myeloproliferative disorders
      (MPD). Giving low doses of chemotherapy, such as fludarabine phosphate, and total-body
      irradiation before a donor peripheral blood stem cell transplant helps stop the growth of
      cancer cells. Giving chemotherapy or radiation therapy before or after transplant also stops
      the patient's immune system from rejecting the donor's stem cells. The donated stem cells may
      replace the patient's immune cells and help destroy any remaining cancer cells
      (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an
      immune response against the body's normal cells. Giving cyclosporine and mycophenolate
      mofetil after the transplant may stop this from happening.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. Decrease the incidence of day-200 hematopoietic cell transplantation (HCT) failure to <
      20% in patients with MDS-Refractory anemia (RA)-(ringed sideroblasts [RS])/MPD and in
      patients with chronic myelomonocytic leukemia (CMML)/refractory anemia with excess blasts
      (RAEB).

      SECONDARY OBJECTIVES:

      I. The rate of relapse/progression in patients with MPD or MDS-RA and those with CMML or
      MDS-RAEB.

      II. The probability of progression free survival (PFS) in patients with MPD or MDS-RA and
      those with CMML or MDS-RAEB.

      III. The kinetics of donor engraftment.

      IV. The incidence of infections.

      OUTLINE: This is a dose-escalation study of total body irradiation (TBI).

      NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously
      (IV) on days -4 to -2 and undergo TBI on day 0.

      PERIPHERAL BLOOD STEM CELL (PBSC) TRANSPLANTATION: Patients undergo filgrastim
      (G-CSF)-mobilized PBSC infusion after TBI on day 0.

      IMMUNOSUPPRESSION:

      Matched Related Donor: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3
      to 56, followed by a taper until day 180. Patients also receive mycophenolate mofetil (MMF)
      PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

      Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper
      until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after
      transplantation on day 0 and continue until day 40, followed by a taper until day 96.

      After completion of study treatment, patients are followed periodically.
    

Intervention name(s): Cyclosporine; Fludarabine Phosphate; Laboratory Biomarker Analysis; Mycophenolate Mofetil; Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Peripheral Blood Stem Cell Transplantation; Total-Body Irradiation
Intervention type(s): Drug; Drug; Other; Drug; Procedure; Procedure; Radiation
Intervention description(s): Given PO; Given IV; Correlative studies; Given PO; Undergo transplantation; Undergo PBSC transplant; Undergo TBI
Other intervention name(s): 27-400; Ciclosporin; CsA; Cyclosporin; Cyclosporin A; Gengraf; Neoral; OL 27-400; Sandimmun; Sandimmune; SangCya; 2-F-ara-AMP; 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-; Beneflur; Fludara; Oforta; SH T 586; Cellcept; MMF; Non-myeloablative allogeneic transplant; Nonmyeloablative Stem Cell Transplantation; NST; PBPC transplantation; Peripheral Blood Progenitor Cell Transplantation; Peripheral Stem Cell Support; Peripheral Stem Cell Transplantation; TOTAL BODY IRRADIATION; Whole-Body Irradiation
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Fludarabine; Fludarabine phosphate; Cyclosporins
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment