Reduced-Intensity Regimen Before Donor Bone Marrow Transplant in Treating Patients With Myelodysplastic Syndromes
Condition: Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms
MeSH terms: Leukemia; Preleukemia; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Photopheresis treats the patient's blood with drugs and ultraviolet light outside
      the body and kills the white blood cells. Giving photopheresis, pentostatin, and radiation
      therapy before a donor bone marrow or stem cell transplant helps stop the patient's immune
      system from rejecting the donor's stem cells. The donated stem cells may replace the
      patient's immune system 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 pentostatin before transplant and cyclosporine or
      mycophenolate mofetil after transplant may stop this from happening.

      PURPOSE: This phase II trial is studying how well giving pentostatin together with
      photopheresis and total-body irradiation work before donor bone marrow transplant in treating
      patients with myelodysplastic syndromes.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the complete response rate in patients with myelodysplastic syndromes treated
           with reduced-intensity allogeneic bone marrow transplantation, including photopheresis,
           total body irradiation, and pentostatin.

        -  Determine the disease-free and overall survival of patients treated with this regimen.

        -  Determine the engraftment rate of donor cells in patients treated with this regimen.

        -  Determine the extent and duration of acute and chronic graft-versus-host disease in
           patients treated with this regimen.

        -  Determine the toxicity of this regimen in these patients.

      OUTLINE: This is a single-arm, two-stage, multicenter phase II study.

        -  Preparative Regimen: Patients undergo photopheresis using methoxsalen on days -7 and -6
           and receive pentostatin intravenously (IV )continuously on days -5 and -4. Total body
           irradiation is administered on days -3 and -2 for a total of 3 doses.

        -  Transplantation: Allogeneic bone marrow or peripheral blood stem cells are infused on
           day 0.

        -  Acute graft-vs-host-disease (GVHD) prophylaxis: Patients receive cyclosporine IV on days
           -1 to 30 and then orally every 12 hours. Cyclosporine dose is then tapered beginning
           after day 50 and continuing for 6 months in the absence of GVHD. Once cyclosporine dose
           is significantly decreased, oral mycophenolate mofetil (MMF) is then administered twice
           a day. MMF dose is then tapered for 12 months in the absence of GVHD. Patients also
           receive methotrexate IV on days 1 and 3.

      Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
      annually thereafter.

      PROJECTED ACCRUAL: A total of 33 patients would be accrued for this study within 2.1 years.
    

Intervention name(s): Cyclosporine; Methotrexate; Photopheresis; Mycofenolate mofetil; Pentostatin; allogeneic bone marrow; peripheral blood stem cell; Total body irradiation
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Procedure; Procedure; Radiation
Intervention description(s): Immunosuppressant; Antimetabolite; Psoralens; an antibiotic with immunosuppressamt properties isolated from Penicillium spp; Purine analogue; Unmanipulated allogeneic bone marrow; G-CSF mobilized peripheral blood stem cell; a total of 600 cGy given in 3 200 cGy fractionated doses
Other intervention name(s): Sandimmune®; cyclosporin A; Neoral®Gengraf®; Gengraf®; CSA; Methotrexate sodium; MTX; Mexate; Mexate-AQ; Folex; Folex PFS; Abitrexate; Rheumatrex; Amethopterin; 8-methoxypsoralen; Uvadex ®; Methoxsalen; Cellcept®; RS-61443; mycophenolic acid; Lilly-68618; MMF; Mycophenolate mofetil; DCF; 2-Deoxycoformycin; Nipent; radiation therapy
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Methotrexate; Pentostatin; Methoxsalen; Cyclosporins
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: chronic myelomonocytic leukemia; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; refractory anemia; refractory anemia with excess blasts; refractory anemia with ringed sideroblasts; secondary myelodysplastic syndromes; atypical chronic myeloid leukemia, BCR-ABL1 negative; myelodysplastic/myeloproliferative neoplasm, unclassifiable