Treo/Flu/TBI With Donor Stem Cell Transplant for Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia
Condition: Acute Myeloid Leukemia in Remission; Chronic Myelomonocytic Leukemia; Minimal Residual Disease; Myelodysplastic Syndrome; Myelodysplastic/Myeloproliferative Neoplasm; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
MeSH terms: Leukemia; Neoplasms; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Neoplasm, Residual; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome
Intervention: Allogeneic Bone Marrow Transplantation; Fludarabine Phosphate; Peripheral Blood Stem Cell Transplantation; Total-Body Irradiation; Treosulfan; Laboratory Biomarker Analysis
Intervention description: Undergo allogeneic bone marrow transplant; Intravenously administered Fludarabine Phosphate; Undergo allogeneic PBSC transplant; Undergo TBI; Intravenously administered Treosulfan; Correlative Studies
Intervention MeSH terms: Fludarabine; Fludarabine phosphate; Treosulfan; Busulfan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 102.0
Sex: All
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well treosulfan and fludarabine phosphate, with or
      without total body irradiation before donor stem cell transplant works in treating patients
      with myelodysplastic syndrome or acute myeloid leukemia. Giving chemotherapy, such as
      treosulfan and fludarabine phosphate, and total-body irradiation before a donor stem cell
      transplant helps stop the growth of cancer cells. It may also stop 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 tacrolimus before and mycophenolate mofetil after the
      transplant may stop this from happening.
    

Eligibility criteria:

        Inclusion Criteria:

          -  MDS, myelodysplastic syndrome/myeloproliferative neoplasia overlap disorders
             (including chronic myelomonocytic leukemia [CMML], and MDS/myeloproliferative neoplasm
             [MPN] unclassifiable syndromes)

          -  AML, other than acute promyelocytic leukemia (APL), in first or second remission or
             with minimal residual disease

          -  With Karnofsky index or Lansky Play-Performance scale > 70% on pre-transplant
             evaluation

          -  Able to give informed consent (if > 18 years), or with a legal guardian capable of
             giving informed consent (if < 18 years)

          -  Patients with previous autologous or allogeneic HCT are allowed to enroll

          -  DONOR: Human leukocyte antigen (HLA)-identical related donors or

          -  DONOR: Unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 as defined by high
             resolution deoxyribonucleic acid (DNA) typing; mismatch for one HLA allele is allowed

          -  DONOR: Donors able to undergo peripheral blood stem cell collection or bone marrow
             harvest

          -  DONOR: Donors in good general health, with a Karnofsky or Lansky play performance
             score > 90%

          -  DONOR: Donors able to give informed consent (if > 18 years), or with a legal guardian
             capable of giving informed consent (if < 18 years)

        Exclusion Criteria:

          -  Receiving umbilical cord blood

          -  With impaired cardiac function as evidenced by ejection fraction < 35% (or, if unable
             to obtain ejection fraction, shortening fraction of < 26%) or cardiac insufficiency
             requiring treatment or symptomatic coronary artery disease; patients with a shortening
             fraction < 26% may be enrolled if approved by a cardiologist

          -  With impaired pulmonary function as evidenced by partial pressure of oxygen (pO2) < 70
             mm Hg and carbon monoxide diffusing capability test (DLCO) < 70% of predicted or pO2 <
             80 mm Hg and DLCO < 60% of predicted; (or, for pediatric patients unable to perform
             pulmonary function tests, then oxygen (O2) saturation < 92% on room air), or receiving
             supplementary continuous oxygen

          -  With impaired renal function as evidenced by creatinine-clearance < 50% for age,
             weight, height or serum creatinine > 2 x upper limit of normal or dialysis-dependent

          -  With hepatic dysfunction as evidenced by total bilirubin > 2.0 x upper limit of normal
             or evidence of synthetic dysfunction or severe cirrhosis

          -  With hepatic dysfunction as evidenced by aspartate aminotransferase (AST) > 2.0 x
             upper limit of normal or evidence of synthetic dysfunction or severe cirrhosis

          -  With active infectious disease requiring deferral of conditioning, as recommended by
             an infectious disease specialist

          -  With human immunodeficiency virus (HIV)-positivity or active infectious hepatitis

          -  With central nervous system (CNS) leukemic involvement not clearing with intrathecal
             chemotherapy, cranial irradiation or both prior to initiating conditioning (day -6)

          -  Patients with active non-hematological malignancies (except non-melanoma skin cancers)
             or those with non-hematological malignancies who have been rendered with no evidence
             of disease, but have a greater than 20% chance of having disease recurrence within 5
             years; this exclusion does not apply to patients with non-hematologic malignancies
             that do not require therapy

          -  With life expectancy severely limited by diseases other than malignancy

          -  Women who are pregnant or lactating

          -  With known hypersensitivity to treosulfan or fludarabine (fludarabine phosphate)

          -  Receiving another experimental drug within 4 weeks before initiation of conditioning
             (day -6)

          -  Unable to give informed consent (if > 18 years) or with a legal guardian (if < 18
             years) unable to give informed consent

          -  DONOR: Individuals deemed unable to undergo marrow harvesting or PBSC mobilization and
             leukapheresis

          -  DONOR: Individuals who are HIV-positive

          -  DONOR: Individuals with active infectious hepatitis

          -  DONOR: Females with a positive pregnancy test

          -  DONOR: Persons unable to give informed consent (if > 18 years) or with a legal
             guardian (if < 18 years) unable to give informed consent