Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia
Condition: Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; 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); Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Blast Crisis; Leukemia, Myeloid, Accelerated Phase; Myelodysplastic Syndromes; Syndrome; Recurrence
Intervention: treosulfan; fludarabine phosphate; total-body irradiation; peripheral blood stem cell transplantation; tacrolimus; allogeneic bone marrow transplantation; allogeneic hematopoietic stem cell transplantation; methotrexate
Intervention description: Given IV; Given IV; Low dose starting at 2Gy; Given IV per institutional standard practice; Given IV or PO; Given IV per institutional standard practice; Given IV per institutional standard practice; Given IV
Intervention MeSH terms: Methotrexate; Fludarabine phosphate; Fludarabine; Treosulfan; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 96.0
Sex: All
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving treosulfan together with fludarabine
      phosphate and total-body irradiation followed by donor stem cell transplant works in treating
      patients with high-risk acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic
      leukemia. Giving chemotherapy, such as treosulfan and fludarabine phosphate, and total-body
      irradiation before a donor bone marrow or peripheral blood 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 and methotrexate before and after transplant may stop this from happening
    

Eligibility criteria:

        Inclusion Criteria:

          -  Acute myeloid leukemia (AML):

               -  All AML patients beyond 1st remission;

               -  Intermediate or high risk AML patients (based on South West Oncology Group [SWOG]
                  cytogenetic criteria) in 1st complete remission

          -  Myelodysplastic syndrome (MDS)

          -  Other myeloid malignancies as chronic myelogenous leukemia (CML), CML accelerated
             phase, CML blast crisis, chronic myelomonocytic leukemia (CMML) (to be approved by
             patient care conference [PCC])

          -  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)

          -  Previous autologous or allogeneic HCT is allowed

          -  Donors must be:

               -  Human leukocyte antigen (HLA)-identical related donors or

               -  Unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 defined by high
                  resolution deoxyribonucleic acid (DNA) typing or mismatched for one HLA allele,
                  except for HLA-C where no mismatch is allowed

               -  Able to undergo peripheral blood stem cell collection or bone marrow harvest

               -  In good general health, with a Karnofsky or Lansky Play Performance score > 90%

               -  Able to give informed consent (if > 18 years), or with a legal guardian capable
                  of giving informed consent (if < 18 years)

          -  Acute lymphoblastic leukemia (ALL): all ALL patients not eligible for other protocols

        Exclusion Criteria:

          -  Receiving umbilical cord blood

          -  With impaired cardiac function as evidenced by ejection fraction < 35% or cardiac
             insufficiency requiring treatment or symptomatic coronary artery disease

          -  With impaired pulmonary function as evidenced by partial pressure of oxygen (pO2) < 70
             mm Hg and diffusing capacity of the lung for carbon monoxide (DLCO) < 70% of predicted
             or pO2 < 80 mm Hg and DLCO < 60% of predicted; or receiving supplementary continuous
             oxygen

          -  With impaired renal function as evidenced by creatinine-clearance < 50% for age,
             weight, height or serum creatinine > 2x upper normal limit or dialysis-dependent

          -  With hepatic dysfunction as evidenced by total bilirubin or aspartate aminotransferase
             (AST) or alanine aminotransferase (ALT) > 2.0 x upper normal limit 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
             because of possible risk of lethal infection when treated with immunosuppressive
             therapy

          -  With central nervous system (CNS) leukemic involvement not clearing with intrathecal
             chemotherapy and/or cranial radiation prior to initiating conditioning (day -6)

          -  With life expectancy severely limited by diseases other than malignancy

          -  Women who are pregnant or lactating because of possible risk to the fetus or infant

          -  With known hypersensitivity to treosulfan and/or fludarabine

          -  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

          -  Ineligible donors will be those:

               -  Deemed unable to undergo marrow harvesting or PBSC mobilization and leukapheresis

               -  Who are HIV-positive

               -  With active infectious hepatitis

               -  Females with a positive pregnancy test

               -  Unable to give informed consent (if > 18 years) or with a legal guardian (if < 18
                  years) unable to give informed consent