A Study of Withdrawal of Immunosuppression and Donor Lymphocyte Infusions Following Allogeneic Transplant for Pediatric Hematologic Malignancies
Condition: Acute Leukemia; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Biphenotypic Leukemia; Pre-leukemic Syndromes; Monosomy 7; Bone Marrow Clonal Malformations; Juvenile Myelomonocytic Leukemia; Myelodysplastic Syndromes; Chronic Myelogenous Leukemia
MeSH terms: Leukemia; Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hematologic Neoplasms; Leukemia, Myelomonocytic, Juvenile; Myelodysplastic Syndromes; Syndrome; Monosomy
Intervention: Withdrawal of immunosuppression and donor lymphocyte infusion
Intervention description: Intervention will involve fast withdrawal of immunosuppression and DLI until full donor chimerism is achieved.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 6 Months
Maximum age: 25 Years
Healthy volunteers: No
Keywords: Hematologic; Malignancy; Leukemia; Pre-leukemic; Allogeneic; Transplant; Pediatric

Summary:

      There is no curative therapy once acute leukemia patients relapse after transplant. Patients
      who develop clinically significant graft versus host disease (GVHD) have a lower rate of
      relapse than those who do not develop GVHD. We are initiating this study of post-transplant
      fast withdrawal of immunosuppression and donor lymphocyte infusions, with a goal of achieving
      full donor chimerism in children with hematologic malignancies. If our hypothesis that full
      donor chimerism results in leukemia-free survival is correct, using immune modulation to
      achieve full donor chimerism should decrease relapse rate and thus increase survival. The
      goal of this Phase II study is to identify if achieving full donor chimerism in whole blood
      CD3+ and leukemia-specific (CD14/15+, CD19+, CD33+ and CD34+) subset may decrease the risk of
      relapse of patients undergoing allogeneic transplant for hematologic malignancy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 6 months - 25 years.

          -  Diagnoses of acute leukemia (AML, ALL, biphenotypic leukemia), pre-leukemic syndromes
             (monosomy 7 or other bone marrow clonal malformations), JMML, myelodysplastic
             syndromes or CML.

          -  Undergoing an allogeneic transplant as standard care.

          -  Performance status: Karnofsky/Lansky>60%.

          -  Availability of pre-transplant recipient's DNA and donor's DNA for chimerism testing.
             This could be DNA or material from which DNA could be extracted. Frozen blood would be
             preferred. For some patients, post transplant specimens that are not infiltrated with
             donor cells may be used.

          -  Bone marrow or PBMTC as stem cell source.HLA matching: donor and recipient should be
             matched at a minimum of 7/8 antigens (A,B,C and DrB1) for bone marrow and PBMTC
             transplants.

          -  No history of ≥grade III acute GVHD.

        Exclusion Criteria:

          -  Treatment on other experimental protocols, if withdrawal of immunosuppression
             interferes with procedures of follow-up on the primary study.

          -  Leukemia relapse defined as > 5% blasts on bone marrow exam or >1% leukemia cells by
             immunoflow MRD, or presence of extramedullary leukemia.

          -  History of acute GVHD ≥ stage III or with any degree of active acute or cGVHD.

          -  On steroids for any reason.

          -  Any condition that compromises compliance with the objectives and procedures of this
             protocol, as judged by the principal investigator.

          -  Cells for DLI cannot be obtained from the donor.