Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Total Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndr

• Status: Completed
• Trial end date: 2019-05-08
• Target enrollment: 0
• Participant gender: All

Summary

This phase II trial studies the side effects and best dose of iodine I 131 monoclonal antibody BC8 when given together with fludarabine phosphate, total-body irradiation, and donor stem cell transplant followed by cyclosporine and mycophenolate mofetil in treating patients with acute myeloid leukemia or myelodysplastic syndrome that has spread to other places in the body and usually cannot be cured or controlled with treatment. Giving chemotherapy drugs, such as fludarabine phosphate, and total-body irradiation before a donor peripheral blood stem cell 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 fludarabine phosphate and total-body irradiation before the transplant together with cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. Giving a radiolabeled monoclonal antibody together with donor stem cell transplant, cyclosporine, and mycophenolate mofetil may be an effective treatment for advanced acute myeloid leukemia or myelodysplastic syndromes.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fred Hutchinson Cancer Research Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Antibodies; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Cadexomer iodine; Cyclosporine; Cyclosporins; Fludarabine; Fludarabine phosphate; Immunoglobulins; Iodine; Mycophenolate mofetil; Mycophenolic Acid; Vidarabine

Criteria

Inclusion Criteria:

• Patients with advanced AML 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 anemia with excess blasts in transformation (RAEBT), refractory cytopenia with multilineage dysplasia (RCMD), RCMD with ringed sideroblasts (RCMD-RS), or chronic myelomonocytic leukemia (CMML)

• Patients not in remission must have CD45-expressing leukemic blasts or myelodysplastic cells; 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 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 an 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 peripheral blood stem cell (PBSC) donation; related donors should be matched by molecular methods at the intermediate resolution level at HLA-A, B, C, and developmentally regulated RNA binding protein 1 (DRB1) according to Fred Hutchinson Cancer Research Center (FHCRC) Standard Practice Guidelines and to the allele level at DQB1; unrelated donors should be identified using matching criteria that follows the FHCRC Standard Practice Guidelines limiting the study to eligible donors that are allele matched for HLA-A, B, C, DRB1, and DQB1 (grade 1), and accepting up to one allele mismatch as per Standard Practice grade 2.1 for HLA-A, B, or C

• DONOR: Donors must meet HLA matching criteria as well as standard SCCA and/or NMDP or other donor center criteria for PBSC donation

Exclusion Criteria:

• Circulating antibody against mouse immunoglobulin (human anti-mouse antibody [HAMA])

• Prior radiation to maximally tolerated levels to any normal organ

• Patients may not have symptomatic coronary artery disease and may not be on cardiac medications for anti-arrhythmic or inotropic effects

• Inability to understand or give an informed consent

• Patients who are seropositive for human immunodeficiency virus (HIV)

• Perceived inability to tolerate diagnostic or therapeutic procedures, particularly treatment in radiation isolation

• Patients who have previously undergone autologous or allogeneic HSCT