Donor Stem Cell Transplant in Treating Patients With Myeloid Cancer or Other Disease
Condition: Leukemia; Myelodysplastic Syndromes
MeSH terms: Leukemia; Preleukemia; Myelodysplastic Syndromes; Syndrome
Intervention: anti-thymocyte globulin; fludarabine phosphate; thiotepa; peripheral blood stem cell transplantation; total-body irradiation
Intervention description: Rabbit thymoglobulin will be given intravenously at a dose of 2.5 mg/kg on days -5,-4, -3, and -2. The first dose of thymoglobulin will be given over six (6) hours and subsequent doses over four (4) or more hours as tolerated or, per institutional anti-thymocyte globulin (ATG) administration guidelines.; Fludarabine 40 mg/m^2/day intravenously (IV) over 30-60 minutes on days -7,-6,-5,-4,-3 (total dose 200 mg/m^2).; Thiotepa 5 mg/kg/day intravenously (IV) over 4 hours on days -8, -7 (total dose 10 mg/kg).; Peripheral Blood Stem Cell (PBSC) Infusion. All patients will receive granulocyte colony-stimulating factor (G-CSF)-mobilized PBSC on day 0 (or day+1 when available) following CD34 cell selection for ex vivo T cell removal. PBSC is infused via a central venous catheter using blood infusion tubing.; The total-body irradiation (TBI) will be given in 2 fractions of 400 cGy each administered on day -10 and -9 via anterior and posterior fields for a total dose of 800 cGy.
Intervention MeSH terms: Fludarabine; Fludarabine phosphate; Thiotepa; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Maximum age: 60 Years
Healthy volunteers: No
Keywords: adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia in remission; childhood acute myeloid leukemia in remission; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; 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); recurrent adult acute myeloid leukemia; recurrent childhood acute myeloid leukemia; secondary acute myeloid leukemia; accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; childhood chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; secondary myelodysplastic syndromes

Summary:

      RATIONALE: Giving total-body irradiation and chemotherapy, such as fludarabine and thiotepa,
      before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It
      also helps stop the patient's immune system from rejecting the donor's stem cells. When
      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 antithymocyte globulin and removing the T cells from the donor cells before transplant
      may stop this from happening.

      PURPOSE: This phase II trial is studying how well a donor stem cell transplant works in
      treating patients with myeloid cancer or other disease.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Primary acute myeloid leukemia (AML)

               -  First complete remission (CR) with high risk features as defined by: failure to
                  achieve remission by day 21 after induction chemotherapy, or the presence of
                  chromosomal abnormalities involving any of the following: -5/de (5q), -7/del(7q),
                  inversion 3q, abnormalities of 11q23, 20q, 21q, del(9q), translocation 6;9,
                  translocation 9;22, abnormalities of 17p, or complex karyotype with > or = 3
                  abnormalities. Complete remission is defined as < 5% blasts in the marrow.

               -  Second CR or subsequent in remission

               -  Refractory or relapsed disease with absolute peripheral blood blasts < 2000/mcL

          -  Secondary AML in remission or relapse

          -  Chronic myelogenous leukemia (CML) in accelerated or blast phase

               -  Accelerated phase is defined by any one of the following:

                    -  Blasts 10% to 19% of peripheral blood white cells or bone marrow cells

                    -  Peripheral blood basophils at least 20%

                    -  Persistent thrombocytopenia (<100 x 10^9/L) unrelated to therapy, or
                       persistent thrombocytosis (>1000 x 10^9/L) unresponsive to therapy

                    -  Increasing spleen size and increasing white blood cell (WBC) count
                       unresponsive to therapy

                    -  Cytogenetic evidence of clonal evolution (i.e., the appearance of an
                       additional genetic abnormality that was not present in the initial specimen
                       at the time of diagnosis of chronic phase CML)

                    -  Resistance to tyrosine kinase inhibitors (imatinib or other) defined as no
                       complete cytogenetic response even if the above criteria are not met.

               -  Blast phase is defined by either of the following:

                    -  Blasts 20% or more of peripheral blood white cells or bone marrow cells

                    -  Extramedullary blast proliferation

                    -  Large foci or clusters of blasts in bone marrow biopsy

          -  Primary myelodysplastic syndrome (MDS) with an IPSS score >1

          -  Secondary MDS with any international prostate symptom score (IPSS)

          -  Age ≤60 years

          -  Co-Morbidity score 0-2

          -  At least 35 days following start of preceding leukemia induction therapy

        Exclusion Criteria:

          -  Patients for whom a suitable HLA genotypically identical sibling or fully matched
             HLA-A, -B, -C, and -DRB1 unrelated donor is available.

          -  Patients greater than 60 years of age.

          -  Hypersensitivity to thymoglobulin.

          -  Symptomatic uncontrolled coronary artery disease or congestive heart failure.

          -  Hepatic disease with transaminases or bilirubin > 2 times upper limit of normal (ULN)
             except for isolated hyperbilirubinemia attributed to Gilbert's syndrome.

          -  Severe hypoxemia with room air - Partial Pressure of Oxygen in Arterial Blood - (PAO2)
             < 70, supplemental oxygen-dependence, or carbon monoxide diffusing capacity (DLCO) <
             50% predicted.

          -  Impaired renal function with creatinine > 2 times upper limit of normal (ULN) or
             creatinine clearance measured by 24-hour urine collection < 50% normal for age,
             gender, and weight.

          -  Patients with central nervous system (CNS) involvement with disease refractory to
             intrathecal chemotherapy.

          -  Patients who are human immunodeficiency virus (HIV) seropositive.

          -  Patients who are pregnant or breast-feeding.

          -  Patients with active infections that are untreated, or failing to respond to
             appropriate therapy.

          -  Karnofsky performance status < 50%.

          -  Prior allogeneic or autologous bone marrow, peripheral blood stem cell, or umbilical
             cord blood transplant.

          -  Inability to provide informed consent.

          -  Co-morbidity score >2

          -  Less than 35 days from start of previous leukemia induction therapy