Radiolabeled BC8 Antibody, Busulfan, Cyclophosphamide Followed by Donor Stem Cell Transplant in Treating Patients With Acute Myelogenous Leukemia in First Remission

Fred Hutchinson Cancer Center18 enrolled

Overview

This phase II trial studies how well iodine I 131 monoclonal antibody BC8, busulfan, and cyclophosphamide followed by donor stem cell transplant works in treating patients with acute myeloid leukemia that has decreased or disappeared, but the cancer may still be in the body. Giving chemotherapy drugs, such as busulfan and cyclophosphamide 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 stem cells from a related donor, that closely matches the patient's blood, are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

PRIMARY OBJECTIVES: I. To determine the efficacy (as measured by survival and disease-free survival) and toxicity of a regimen of busulfan 16 mg/kg and cyclophosphamide 120 mg/kg plus 131I-labeled anti-cluster of differentiation (CD) 45 antibody (iodine I 131 monoclonal antibody BC8) (delivering a dose of 5.25 gray \[Gy\] to the normal organ receiving the highest dose) in patients with acute myeloid leukemia (AML) in first remission receiving human leukocyte antigen (HLA)-identical related peripheral blood stem cell (PBSC) transplants. OUTLINE: RADIOLABELED ANTIBODY: Patients receive iodine I 131 monoclonal antibody BC8 intravenously (IV) on day -13. CHEMOTHERAPY: Patients receive busulfan orally (PO) every 6 hours on days -7 to -4 and cyclophosphamide IV on days -3 and -2. TRANSPLANT: Patients undergo allogeneic PBSC or bone marrow (BM) transplant on day 0. GRAFT-VS-HOST DISEASE PREVENTION: Patients receive cyclosporine IV or PO every 12 hours on days -1 to 50 with a taper to day 180. Patients also receive methotrexate IV on days 1, 3, 6, and 11. After completion of study treatment, patients are followed up at 6, 9, and 12 months; every 6 months for 1 year; and then yearly thereafter.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Interventions

iodine I 131 monoclonal antibody BC8RADIATION

Given IV

busulfanDRUG

Given PO

cyclophosphamideDRUG

Given IV

allogeneic bone marrow transplantationPROCEDURE

Undergo allogeneic PBSC or bone marrow transplant

allogeneic hematopoietic stem cell transplantationPROCEDURE

Undergo allogeneic PBSC or bone marrow transplant

peripheral blood stem cell transplantationPROCEDURE

Undergo allogeneic PBSC or bone marrow transplant

cyclosporineDRUG

Given IV or PO

methotrexateDRUG

Given IV

laboratory biomarker analysisOTHER

Correlative studies

Eligibility

Sex: ALLMin age: 16 YearsMax age: 55 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients with AML in first remission * Creatinine \< 2.0 mg/dl * Bilirubin \< 1.5 mg/dl which is expected to exclude patients at high risk of developing veno-occlusive disease of the liver * Aspartate aminotransferase (AST) \< 1.5 times the upper limit of normal which is expected to exclude patients at high risk of developing veno-occlusive disease of the liver * Patients must have an expected survival of \> 60 days and must be free of major infection * DONOR: genotypic or phenotypic HLA-matched family members; related donors should be matched by molecular methods at the intermediate resolution level at HLA-A, B, C, and DR beta 1 (DRB1) according to Fred Hutchinson Cancer Research Center (FHCRC) Standard Practice Guidelines and to the allele level at DQ beta 1 (DQB1) Exclusion Criteria: * Patients with history of or current leukemic involvement of the central nervous system (CNS) * Prior radiation to maximally tolerated levels to any normal organ * 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 * Circulating antibody against mouse immunoglobulin * DONOR: unrelated donors and donors mismatched for 1 or more HLA antigens * DONOR: donors who for psychologic, physiologic or medical reasons are unable to undergo filgrastim (G-CSF)- mobilized PBSC collection or marrow harvesting * DONOR: donors who are seropositive for HIV

Locations (3)

Pacific Northwest National Laboratory

Richland, Washington, United States

VA Puget Sound Health Care System

Seattle, Washington, United States

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

Outcomes

Primary Outcomes

Disease-free survival (DFS)

Summarized using appropriate time-to-event methods with estimates of the corresponding confidence intervals provided.

Time frame: Up to 6 years

Secondary Outcomes

Overall survival (OS)

Summarized using appropriate time-to-event methods with estimates of the corresponding confidence intervals provided.

Time frame: Up to 6 years

Relapse of AML patients

Summarized using appropriate time-to-event methods with estimates of the corresponding confidence intervals provided.

Time frame: Up to 6 years

Transplant-related mortality

Transplant-related toxicities are graded using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 2. Summarized using appropriate time-to-event methods with estimates of the corresponding confidence intervals provided.

Time frame: Up to 6 years

Radiolabeled BC8 Antibody, Busulfan, Cyclophosphamide Followed by Donor Stem Cell Transplant in Treating Patients With Acute Myelogenous Leukemia in First Remission

Overview

Conditions

Interventions

Eligibility

Locations (3)

Outcomes

Primary Outcomes

Secondary Outcomes