Selective Depletion of CD45RA+T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of GVHD
Condition: Graft Versus Host Disease; Leukemia; Myelodysplastic Syndromes
MeSH terms: Leukemia; Preleukemia; Myelodysplastic Syndromes; Graft vs Host Disease; Syndrome
Intervention: Fludarabine Phosphate; Tacrolimus; Thiotepa; Total-Body Irradiation (TBI); Magnetic Affinity Cell Sorting; Peripheral Blood Stem Cell Transplantation; Allogeneic Hematopoietic Stem Cell Transplantation; T Cell-Depleted Hematopoietic Stem Cell Transplantation
Intervention description: Fludarabine will be administered in a dose of 25 mg/m2/day IV over approximately 30 minutes for 5 consecutive days (day -6 to -2). The total dose of fludarabine will be 125 mg/m2.; Tacrolimus will be administered beginning on day -1 at a dose of 0.03 mg/kg/day by continuous IV infusion.
For the first cohort of 35 patients, if there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus should then be tapered at the rate of approximately 5% of the day 50 dose each week for liquid, and 20% of the day 50 dose per month for capsules.
In the second cohort of 25 patients if there is no evidence of grade II GVHD on or prior to day 30, tacrolimus should then be tapered at the rate of approximately 8% of the day 30 dose each week for liquid, and 33% of the day 30 dose per month for capsules.; Thiotepa will be administered in a dose of 5 mg/kg/day (adjusted body weight) IV over approximately 4 hours for 2 consecutive days (day -6 and day -5).; TBI will be given as 165 cGy fractions twice per day x 4 days - total dose 1320cGy (days -10 to -7).; Device; Patient will undergo a PBSC transplantation; Patients who are considered appropriate candidates for allogeneic hematopoietic stem cell transplantation; Patients who are eligible will receive a T Cell-Depleted Hematopoietic Stem Cell Transplantation
Intervention MeSH terms: Fludarabine; Fludarabine phosphate; Thiotepa; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 14 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: graft versus host disease; adult acute lymphoblastic leukemia in remission; recurrent adult acute lymphoblastic leukemia; childhood acute lymphoblastic leukemia in remission; recurrent childhood acute lymphoblastic leukemia; adult acute myeloid leukemia in remission; recurrent adult acute myeloid leukemia; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; 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); childhood acute myeloid leukemia in remission; recurrent childhood acute myeloid leukemia; childhood myelodysplastic syndromes; previously treated myelodysplastic syndromes; refractory anemia with excess blasts; de novo myelodysplastic syndromes; secondary myelodysplastic syndromes

Summary:

      RATIONALE: Allogeneic hematopoietic stem cell transplant (HSCT) is a treatment that can cure
      acute leukemia and myelodysplasia. After giving the patient chemotherapy and total body
      irradiation to stop the growth of cancer and remove the patient's diseased bone marrow,
      healthy stem cells from a donor are infused into the patient to replace the patient's bone
      marrow and make red and white blood cells and platelets. Unfortunately HSCT is often
      complicated by 'graft versus host disease' (GVHD) in which the transplanted cells from a
      donor can make an immune response against the body's normal cells and cause tissue damage and
      severe symptoms. Removing a subset of the donor T cells, called 'naive T cells', before
      transplant may reduce the frequency and intensity of GVHD.

      PURPOSE: This phase II trial will determine whether the removal of the naive T cells from
      donor cells can decrease the rate and severity of graft-vs-host disease while preserving
      specific immunity against infections in patients with acute leukemia or advanced
      myelodysplastic syndromes.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of 1 of the following:

               -  Acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) in first or
                  subsequent remission

               -  ALL or AML in relapse or primary refractory ALL or AML with a circulating blast
                  count ≤ 10,000/mm^3

               -  Refractory anemia with excess blasts (RAEB) (RAEB-1 or RAEB-2) if the patient has
                  received induction chemotherapy within the past 60 days

          -  Appropriate candidate for allogeneic hematopoietic stem cell transplantation (HSCT)

          -  No CNS involvement refractory to intrathecal chemotherapy and/or standard
             cranial-spinal radiotherapy

        PATIENT CHARACTERISTICS:

          -  Age 14-55

          -  Creatinine < 1.5 mg/dL

          -  Cardiac ejection fraction > 45%

          -  DLCO corrected > 60% of predicted

          -  Total bilirubin < 2 times upper limit of normal (ULN) (unless attributed to Gilbert
             syndrome)

          -  AST and ALT < 2 times ULN

          -  Not pregnant or nursing

          -  Fertile patients must use effective contraception during and for 12 months after
             transplantation

          -  HIV negative

          -  No co-existing disease (other than leukemia or RAEB) that would limit life expectancy
             to < 3 months

          -  No uncontrolled infection that, in the opinion of the consulting infectious disease
             physician, would contraindicate myeloablative HSCT

          -  No other medical condition that would contraindicate HSCT

          -  No known hypersensitivity to tacrolimus

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  No prior HSCT

          -  No concurrent participation in other experimental studies for the prevention of
             graft-vs-host disease

        DONOR CHARACTERISTICS:

          -  Genotypic or phenotypic HLA-identical related donor

          -  Able to donate peripheral blood stem cells

          -  Age > 14 years

          -  Applicable to male patients only: No female donors who have previously given birth to
             a male child or have had a pregnancy beyond the first trimester miscarriage or
             termination of pregnancy or nursing

          -  No donors who have received blood transfusions

          -  No CD45 Mutation with aberrant CD45RA isoform expression