Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation and Donor Bone Marrow Transplant in Treating Patients With Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or High-Risk Myelodysplastic Syndrome
Condition: Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; CD45-Positive Neoplastic Cells Present; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Anemia; Myelodysplastic Syndromes; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Leukopenia; Thrombocytopenia; Syndrome
Intervention: Allogeneic Bone Marrow Transplantation; Cyclophosphamide; Fludarabine Phosphate; Iodine I 131 Monoclonal Antibody BC8; Laboratory Biomarker Analysis; Mycophenolate Mofetil; Tacrolimus; Total-Body Irradiation
Intervention description: Given via central line; Given IV; Given IV; Given IV (dosimetry dose) or via central line (therapeutic dose); Correlative studies; Given IV or PO; Given IV or PO; Undergo TBI
Intervention MeSH terms: Iodine; Mycophenolic Acid; Cadexomer iodine; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Antineoplastic Agents, Immunological; Tacrolimus; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase I trial studies the side effects and best dose of iodine I 131monoclonal antibody
      BC8 when given together with fludarabine phosphate, cyclophosphamide, total-body irradiation,
      and donor bone marrow transplant, and to see how well they work in treating patients with
      acute myeloid leukemia or acute lymphoblastic leukemia that has spread to nearby or other
      places in the body (advanced), or high-risk myelodysplastic syndrome. Giving chemotherapy
      drugs, such as fludarabine phosphate and cyclophosphamide, and total-body irradiation before
      a donor bone marrow transplant helps stop the growth of cancer or abnormal cells and helps
      stop the patient's immune system from rejecting the donor's stem cells. Also, radiolabeled
      monoclonal antibodies, such as iodine I 131 monoclonal antibody BC8, can find cancer cells
      and carry cancer-killing substances to them without harming normal 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. Sometimes the
      transplanted cells from a donor can make an immune response against the body's normal cells.
      Giving cyclophosphamide together with mycophenolate mofetil and tacrolimus after the
      transplant may stop this from happening. Giving a radiolabeled monoclonal antibody together
      with donor stem cell transplant, fludarabine phosphate, cyclophosphamide, mycophenolate
      mofetil, and tacrolimus may be an effective treatment for advanced acute myeloid leukemia,
      acute lymphoblastic leukemia, or myelodysplastic syndromes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with advanced AML or ALL defined as beyond first remission, primary
             refractory disease, or evolved from myelodysplastic or myeloproliferative syndromes;
             or patients with MDS expressed as refractory anemia with excess blasts (RAEB),
             refractory cytopenia with multilineage dysplasia (RCMD), RCMD with ringed sideroblasts
             (RCMD-RS), or chronic myelomonocytic leukemia (CMML)

          -  Patients not in remission must have cluster of differentiation (CD)45-expressing
             leukemic blasts; patients in remission do not require phenotyping and may have
             leukemia previously documented to be CD45 negative (because in remission patients,
             virtually all antibody binding is to non-malignant cells which make up >= 95% of
             nucleated cells in the marrow)

          -  Patients should have a circulating blast count of less than 10,000/mm^3 (control with
             hydroxyurea or similar agent is allowed)

          -  Patients must have a creatinine clearance greater than 50/ml per minute by the
             following formula (test must be performed within 28 days prior to registration):

               -  Creatinine clearance (CrCl) = (140-age) (Wt in Kg) x 0.85 (female) OR 1.0
                  (male)/72 x serum Cr

          -  Bilirubin < 2 times the upper limit of normal

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 times the
             upper limit of normal

          -  Karnofsky score >= 70 or Eastern Cooperative Oncology Group (ECOG) =< 2

          -  Patients must have an expected survival of > 60 days and must be free of active
             infection

          -  Patients must have a related donor who is identical for one human leukocyte antigen
             (HLA) haplotype and mismatched at the HLA-A, -B or class II, DR beta 1 (DRB1) loci of
             the unshared haplotype with the exception of single HLA-A, -B or DRB1 mismatches

          -  DONOR: Related donor who is identical for one HLA haplotype and mismatched at the
             HLA-A, -B, or DRB1 loci of the unshared haplotype with the exception of single HLA-A,
             -B, or DRB1 mismatches

        Exclusion Criteria:

          -  Circulating antibody against mouse immunoglobulin (HAMA)

          -  Prior radiation to maximally tolerated levels to any critical normal organ

          -  Cross-match positive with donor

          -  Patients may not have symptomatic coronary artery disease and may not be on cardiac
             medications for anti-arrhythmic or inotropic effects

          -  Left ventricular ejection fraction < 35%

          -  Corrected diffusion capacity of carbon monoxide (DLCO) < 35% and/or receiving
             supplemental continuous oxygen

          -  Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of
             portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy,
             uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the
             prothrombin time, ascites related to portal hypertension, bacterial or fungal liver
             abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary disease

          -  Patients who are known seropositive for human immunodeficiency virus (HIV)

          -  Perceived inability to tolerate diagnostic or therapeutic procedures, particularly
             treatment in radiation isolation

          -  Central nervous system (CNS) involvement with disease refractory to intrathecal
             chemotherapy and/or standard cranial-spinal radiotherapy

          -  Women of childbearing potential who are pregnant (beta-human chorionic gonadotropin
             positive [b-HCG+]) or breast feeding

          -  Fertile men and women unwilling to use contraceptives during and for 12 months
             post-transplant

          -  Inability to understand or give an informed consent