Yttrium-90 Anti-CD45 Monoclonal Antibody BC8 Followed by Donor Stem Cell Transplant in Treating Patients With High-Risk AML, ALL, or MDS
Condition: Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Secondary Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Myelodysplastic Syndromes; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Recurrence
Intervention: Allogeneic Bone Marrow Transplantation; Allogeneic Hematopoietic Stem Cell Transplantation; Cyclosporine; Fludarabine Phosphate; Indium In 111 Anti-CD45 Monoclonal Antibody BC8; Laboratory Biomarker Analysis; Mycophenolate Mofetil; Peripheral Blood Stem Cell Transplantation; Pharmacological Study; Total-Body Irradiation; Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8
Intervention description: Undergo allogeneic bone marrow transplant; Undergo allogeneic PBSC or bone marrow transplant; Given PO or IV; Given IV; Given IV (dosimetric dose); Correlative studies; Given PO or IV; Undergo allogeneic PBSC transplant; Correlative studies; Undergo TBI; Given via central line (therapeutic dose)
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Antineoplastic Agents, Immunological; Fludarabine; Fludarabine phosphate; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Cyclosporins
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase I trial studies the side effects and maximum tolerated dose of yttrium Y 90
      anti-cluster of differentiation 45 (CD45) monoclonal antibody BC8 (90Y-BC8) followed by donor
      stem cell transplant in treating patients with acute myeloid leukemia (AML), acute
      lymphoblastic leukemia (ALL), or myelodysplastic syndrome (MDS) that is likely to come back
      or spread. Giving chemotherapy drugs, such as fludarabine phosphate (FLU), and total-body
      irradiation (TBI) before a donor peripheral blood stem cell (PBSC) or 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. Radiolabeled monoclonal antibodies, such as 90Y-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 FLU, 90Y-BC8, and TBI before the transplant together with cyclosporine
      and mycophenolate mofetil after the transplant may stop this from happening.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have advanced AML, ALL or high-risk MDS meeting one of the following
             descriptions:

               -  AML or ALL beyond first remission (i.e., having relapsed at least one time after
                  achieving remission in response to a treatment regimen)

               -  AML or ALL representing primary refractory disease (i.e., having failed to
                  achieve remission at any time following one or more prior treatment regimens)

               -  AML evolved from myelodysplastic or myeloproliferative syndromes; or

               -  MDS expressed as refractory anemia with excess blasts (RAEB) or chronic
                  myelomonocytic leukemia (CMML) by French-American-British (FAB) criteria

          -  Patients not in remission must have CD45-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 an estimated creatinine clearance greater than 50/ml per minute
             (serum creatinine value must be within 28 days prior to registration)

          -  Bilirubin < 2 times the upper limit of normal

          -  Aspartate aminotransferase (AST) and alanine transaminase (ALT) < 2 times the upper
             limit of normal

          -  Eastern Cooperative Oncology Group (ECOG) =< 2 or Karnofsky >= 70

          -  Patients must have an expected survival of > 60 days and must be free of active
             infection

          -  Patients must have an human leukocyte antigen (HLA)-identical sibling donor or an
             HLA-matched unrelated donor who meets standard Seattle Cancer Care Alliance (SCCA)
             and/or National Marrow Donor Program (NMDP) or other donor center criteria for PBSC or
             bone marrow donation, as follows:

               -  Related donor: related to the patient and genotypically or phenotypically
                  identical for HLA-A, B, C, DRB1 and DQB1; phenotypic identity must be confirmed
                  by high-resolution typing

               -  Unrelated donor:

                    -  Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing; OR
                       mismatched for a single allele without antigen mismatching at HLA-A, B or C
                       as defined by high resolution typing but otherwise matched for HLA-A, B, C,
                       DRB1 and DQB1 by high resolution typing

                    -  Doors are excluded when preexisting immunoreactivity is identified that
                       would jeopardize donor hematopoietic cell engraftment; this determination is
                       based on the standard practice of the individual institution; the
                       recommended procedure for patients with 10 of 10 HLA allele level
                       (phenotypic) match is to obtain panel reactive antibody (PRA) screens to
                       class I and class II antigens for all patients before hematopoietic cell
                       transplant (HCT); if the PRA shows > 10% activity, then flow cytometric or B
                       and T cell cytotoxic cross matches should be obtained; the donor should be
                       excluded if any of the cytotoxic cross match assays are positive; for those
                       patients with and HLA class I allele mismatch, flow cytometric or B and T
                       cell cytotoxic cross matches should be obtained regardless of the PRA
                       results; a positive anti-donor cytotoxic crossmatch is an absolute donor
                       exclusion

                    -  Patient and donor pairs homozygous at a mismatched allele in the graft
                       rejection vector are considered a two-allele mismatch; i.e., the patient is
                       A*0101 and the donor is A*0102, and this type of mismatch is not allowed

          -  DONOR: Donors must meet HLA matching criteria and standard SCCA and/or National Marrow
             Donor Program (NMDP) or other donor center criteria for PBSC or bone marrow donation

        Exclusion Criteria:

          -  Circulating human anti-mouse antibody (HAMA)

          -  Prior radiation to maximally tolerated levels to any critical normal organ, or > 20 Gy
             prior radiation to large areas of the bone marrow (e.g., external radiation therapy to
             whole pelvis)

          -  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 lung capacity of carbon monoxide (DLCO) < 35% 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 to be seropositive for human immunodeficiency virus (HIV)

          -  Perceived inability to tolerate diagnostic or therapeutic procedures

          -  Active central nervous system (CNS) leukemia at time of treatment

          -  Women of childbearing potential who are pregnant (beta-human chorionic gonadotropin
             positive [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