Donor Peripheral Stem Cell Transplant and Donor Natural Killer Cell Transplant After Total-Body Irradiation, Thiotepa, Fludarabine, and Muromonab-CD3 in Treating Patients With Leukemia or Other Blood Diseases
Condition: Graft Versus Host Disease; Leukemia; Myelodysplastic Syndromes
MeSH terms: Leukemia; Preleukemia; Myelodysplastic Syndromes; Graft vs Host Disease; Syndrome
Intervention: muromonab-CD3; natural killer cell therapy; fludarabine phosphate; methotrexate; thiotepa; gene expression analysis; flow cytometry; immunologic technique; allogeneic hematopoietic stem cell transplantation; in vitro-treated peripheral blood stem cell transplantation; total-body irradiation
Intervention MeSH terms: Methotrexate; Fludarabine phosphate; Fludarabine; Thiotepa; Muromonab-CD3
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Maximum age: 45 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 with 11q23 (MLL) abnormalities; adult acute myeloid leukemia in remission; recurrent adult acute myeloid leukemia; childhood acute myeloid leukemia in remission; recurrent childhood acute myeloid leukemia; secondary acute myeloid leukemia; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; childhood chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; 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 myelodysplastic syndromes

Summary:

      RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood
      stem cell and donor natural killer cell transplant helps stop the growth of cancer and
      abnormal cells and helps stop the patient's immune system from rejecting the donor's stem
      cells. When certain 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. Removing the T cells from the donor cells before transplant may stop this from
      happening.

      PURPOSE: This phase II trial is studying how well giving a donor peripheral stem cell
      transplant and a donor natural killer cell transplant after total-body irradiation, thiotepa,
      fludarabine, and muromonab-CD3 works in treating patients with leukemia or other blood
      diseases.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of 1 of the following life-threatening hematological malignancies:

               -  Acute lymphoblastic leukemia meeting 1 of the following criteria:

                    -  Advanced beyond first remission

                    -  In first remission with high-risk prognostic features, including any of the
                       following:

                         -  Philadelphia chromosome-positive disease

                         -  Chromosome 11q23 abnormality

                         -  Hypodiploid

                         -  Failed to achieve first remission within 1 month after induction

               -  Acute myeloid leukemia (AML) meeting 1 of the following criteria:

                    -  Advanced beyond first remission

                    -  First remission with high-risk prognostic features, including any of the
                       following:

                         -  Chromosome 11q23 abnormality

                         -  Chromosome del 7q

                         -  Secondary AML

                         -  Failed to achieve first remission within 1 month after induction

               -  Myelodysplastic syndromes with International Prognostic Score > 1

               -  Chronic myelogenous leukemia in accelerated or blastic phase

          -  No active CNS disease

          -  No suitable HLA-matched related or unrelated donor available

          -  Haploidentical family member available as donor of partially HLA-matched peripheral
             blood stem cells

               -  Least degree of mismatch to HLA-A, B, C, DRB1, and DQB1

               -  No mismatch for a single HLA-A, B, C, DRB1, or DQB1 antigen

               -  Donor killer cell immunoglobulin-like receptor ligand group expression preferably
                  different than patient

        PATIENT CHARACTERISTICS:

          -  LVEF ≥ 45%

          -  DLCO ≥ 60% of predicted

          -  AST and ALT ≤ 2 times upper limit of normal (ULN) (unless due to malignancy)

          -  Bilirubin ≤ 2 times ULN (unless due to malignancy)

          -  No life expectancy < 6 months due to coexisting disease other than the malignancy

          -  No active infection (e.g., polymerase chain reaction [PCR] evidence for
             cytomegalovirus, human herpes virus 6, or invasive fungal infection)

          -  No prior infections without evidence of resolution by PCR or imaging studies within
             the past 2 months

          -  No hypersensitivity to murine antibodies

          -  No known HIV positivity

          -  Not pregnant or nursing

          -  Fertile patients must use effective contraception

        PRIOR CONCURRENT THERAPY:

          -  No prior marrow transplantation with total body irradiation > 400 cGy

          -  No concurrent therapies for seizure disorder

          -  No growth factors for 21 days after transplantation