HLA-Nonidentical Stem Cell and Natural Killer Cell Transplantation for Children Less the Two Years of Age With Hematologic Malignancies
Condition: Acute Myeloid Leukemia; Acute Lymphocytic Leukemia; Myelodysplasia; Chronic Myeloid Leukemia; Histiocytosis
MeSH terms: Leukemia; Leukemia, Myeloid; Hematologic Neoplasms; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Histiocytosis
Intervention: Chemotherapy and antibodies; Miltenyi Biotec CliniMACS; Allogeneic stem cell transplantation
Intervention description: Study participants will receive a non-TBI based preparative regimen consisting of Cyclophosphamide, fludarabine, thiotepa, melphalan, and muromonab-CD3 (OKT3) followed by an infusion of a T-lymphocyte depleted haploidentical hematopoietic stem cell graft. Seven days posttransplant, participants will receive an infusion of additional donor derived cells called NK cells.; Stem cell selection device; Allogeneic natural killer (NK)cell infusion
Intervention MeSH terms: Cyclophosphamide; Melphalan; Thiotepa; Fludarabine; Antibodies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Maximum age: 24 Months
Healthy volunteers: No
Keywords: Stem cell transplantation; Stem cell transplant; Haploidentical transplant

Summary:

      Recent studies of conventional chemotherapy for infants with high-risk hematologic
      malignancies show that the long-term disease-free survival is low. Although blood and marrow
      stem cell transplantation using an HLA identical sibling has improved the outcome for these
      children, less than 25% have this donor source available. Another option is haploidentical
      transplantation using a partially matched family member donor (i.e. parental donor).

      Although haploidentical transplantation has proven curative for some patients, this procedure
      has been hindered by significant complications, primarily regimen-related toxicity including
      infection and graft versus host disease (GVHD). Building on prior institutional trials, this
      study will provide patients a haploidentical graft depleted of T lymphocytes using the
      investigational device, CliniMACS selection system. One week after the transplant procedure,
      patients will also receive an infusion of additional donor derived white blood cells called
      Natural Killer (NK) cells in an effort to decrease risks for rejection of the graft, disease
      relapse, and regimen related toxicity. The primary objective of the study is to evaluate 1
      year survival in infants with high risk hematologic malignancies who receive this study
      treatment.
    

Eligibility criteria:

        Inclusion Criteria:

        Must have one of the following diagnosis:

          -  AML in remission or relapse (e.g., FAB M7 or biphenotypic leukemia)

          -  High-risk ALL in first remission (e.g., poor responder to prednisone, Ph+ ALL)

          -  ALL beyond first remission

          -  Secondary leukemia

          -  Primary myelodysplasia (including RAEB, RAEB-T, CMML, JCML, and JMML)

          -  Chronic myeloid leukemia

          -  Histiocytoses (including multi-system Langerhans' cell histiocytosis and
             hemophagocytic lymphohistiocytosis

        Inclusion criteria Donor research participants

          -  HIV negative (date).

          -  Hepatitis B surface antigen negative (date).

          -  Hepatitis C antibody negative (date).

          -  Syphilis negative (date).

          -  Donor is equal to or greater than 3 on 6 HLA match (date).

          -  Not pregnant (negative pregnancy test).

          -  Not lactating.

          -  At least 18 years of age.

        Exclusion Criteria

          -  Patients greater than 24 months of age at the time of transplant.

          -  HLA-identical sibling donor is available.

          -  Cardiac function: shortening fraction <25%.

          -  Pulse oximetry oxygen saturation <92% on room air.

          -  Glomerular filtration rate less than 40 ml/min/1.73 m2 (may use Technetium-99 result
             for GFR).

          -  Direct bilirubin > 3 mg/dl.

          -  SGPT > 500 U/L.

          -  Patients with previous allergy to mouse proteins.

          -  Patients with previous allergy to rabbit serum products.

          -  Patients with Down's syndrome