Busulfan, Cyclophosphamide, and Melphalan or Busulfan and Fludarabine Phosphate Before Donor Hematopoietic Cell Transplant in Treating Younger Patients With Juvenile Myelomonocytic Leukemia
Condition: Juvenile Myelomonocytic Leukemia
MeSH terms: Leukemia; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile
Intervention: Allogeneic Hematopoietic Stem Cell Transplantation; Busulfan; Cyclophosphamide; Fludarabine Phosphate; Laboratory Biomarker Analysis; Melphalan; Mycophenolate Mofetil; Pharmacological Study; Tacrolimus
Intervention description: Undergo allogeneic HCT; Given IV; Given IV; Given IV; Correlative studies; Given IV; Given IV or PO; Correlative studies; Given IV or PO
Intervention MeSH terms: Mycophenolic Acid; Cyclophosphamide; Melphalan; Busulfan; Mechlorethamine; Nitrogen Mustard Compounds; Fludarabine; Fludarabine phosphate; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 3 Months
Maximum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well giving busulfan, cyclophosphamide, and
      melphalan or busulfan and fludarabine phosphate before donor hematopoietic cell transplant
      works in treating younger patients with juvenile myelomonocytic leukemia. Giving chemotherapy
      before a donor hematopoietic transplant helps stop the growth of cancer cells. It may also
      stop the patient's immune system from rejecting the donor's stem cells. When the 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. It is not yet known whether
      giving busulfan, cyclophosphamide, and melphalan or busulfan and fludarabine phosphate before
      a donor stem cell transplant is more effective in treating juvenile myelomonocytic leukemia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a strong clinical suspicion of JMML, based on a modified category 1
             of the revised diagnostic criteria; specifically, eligible patients must have all of
             the following:

               -  Splenomegaly

               -  Absolute monocyte count (AMC) > 1000/uL

               -  Blasts in peripheral blood (PB)/bone marrow (BM) < 20%

          -  For the 7-10% of patients without splenomegaly, the diagnostic entry criteria must
             include all other features described above and at least 2 of the following criteria:

               -  Circulating myeloid precursors

               -  White blood cell (WBC) > 10,000/uL

               -  Increased fetal hemoglobin (HgbF) for age

               -  Sargramostim (GM-CSF) hypersensitivity OR, patients must have been previously
                  diagnosed with JMML

          -  Patients must be previously untreated with HCT

          -  All patients and/or their parents or legal guardians must sign a written informed
             consent

          -  All institutional, Food and Drug Administration (FDA), and National Cancer Institute
             (NCI) requirements for human studies must be met

        Exclusion Criteria:

          -  Patients with a known germline mutation of PTPN11 (Noonan?s Syndrome) are not eligible

          -  Patients with a known history of NF1 (Neurofibromatosis Type 1) and either

               -  A history of a tumor of the central nervous system (astrocytoma or optic glioma),
                  or

               -  A malignant peripheral nerve sheath tumor with a complete remission of < 1 year
                  are not eligible

          -  Human immunodeficiency virus (HIV) positive patients are not eligible