Decitabine and Total-Body Irradiation Followed By Donor Bone Marrow Transplant and Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
Condition: Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      This phase II trial studies how well decitabine and total-body irradiation followed by donor
      bone marrow transplant and cyclophosphamide works in treating patients with relapsed or
      refractory acute myeloid leukemia. Giving decitabine and total-body irradiation before a
      donor bone marrow transplant helps stop the growth of cancer cells. It may also stop the
      patient's immune system from rejecting the donor's stem cells. When the healthy stem cells
      from a donor are infused into the patient they may help the patient's bone marrow make stem
      cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells
      from a donor can make an immune response against the body's normal cells. Giving decitabine
      and total-body irradiation before the transplant together with high-dose cyclophosphamide,
      tacrolimus, and mycophenolate mofetil after the transplant may stop this from happening.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To determine overall survival at 100 days after transplantation following decitabine and a
      bone marrow transplant using a donor that is at least partially-matched and a myeloablative
      preparative regimen with post-transplantation cyclophosphamide for graft-versus-host disease
      (GVHD) prophylaxis.

      SECONDARY OBJECTIVES:

      I. Patients enrolled in this study will also be followed for the following endpoints:
      neutrophil and platelet recovery, graft failure, acute graft-versus-host disease (GVHD),
      chronic GVHD, incidence of infection, treatment-related mortality, time to
      relapse/progression, overall survival, and progression-free survival.

      OUTLINE:

      Beginning between days -29 and -22, patients receive decitabine intravenously (IV) over 1
      hour daily for 10 days, fludarabine phosphate IV over 30 minutes on days -5 to -2, and
      busulfan IV over 3 hours on days -5 to -2.

      PREPARATIVE REGIMEN: Patients undergo total-body irradiation twice daily (BID) on day -1.

      TRANSPLANT: Patients undergo allogeneic bone marrow transplant on day 0.

      GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 2 hours on days 3 and 4,
      tacrolimus orally (PO) BID or IV continuously on days 5-180, mycophenolate mofetil PO three
      times daily (TID) on days 5-35 and filgrastim subcutaneously (SC) beginning day 5 until
      absolute neutrophil count (ANC) >= 1,000/mm^3 for 3 consecutive days.

      After completion of study treatment, patients are followed up at 6 months and 1 year.
    

Intervention name(s): decitabine; fludarabine phosphate; busulfan; cyclophosphamide; tacrolimus; mycophenolate mofetil; filgrastim; total-body irradiation; allogeneic bone marrow transplantation; laboratory biomarker analysis
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Biological; Radiation; Procedure; Other
Intervention description(s): Given IV; Given IV; Given IV; Given IV; Given PO or IV; Given PO; Given SC; Undergo total-body irradiation; Undergo allogeneic bone marrow transplantation; Correlative studies
Other intervention name(s): 5-aza-2'-deoxycytidine (5-aza-dCyd); 5-azacytidine (5AZA); decitabine (DAC); Fludarabine phosphate (2-F-ara-AMP); Beneflur; Fludara; busulfan (BSF); busulfan (BU); Misulfan; Mitosan; Myeloleukon; cyclophosphamide (CPM); cyclophosphamide (CTX); Cytoxan; Endoxan; Endoxana; tacrolimus (FK 506); Prograf; Cellcept; mycophenolate mofetil (MMF); granulocyte-colony stimulating factor (G-CSF); Neupogen; total body irradiation (TBI); bone marrow therapy, allogeneic; bone marrow therapy, allogenic; transplantation, allogeneic bone marrow; transplantation, allogenic bone marrow
Intervention MeSH terms: Vidarabine; Mycophenolic Acid; Cyclophosphamide; Busulfan; Fludarabine; Fludarabine phosphate; Azacitidine; Decitabine; Tacrolimus; Lenograstim
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment