Radiolabeled BC8 (Anti-CD45) Antibody Combined With Cyclophosphamide and Total Body Irradiation Followed by HLA-matched Related or Unrelated Stem Cell Transplantation as Treatment for Advanced Acute Myeloid Leukemia and Myelodysplastic Syndrome
cyclophosphamide
+ methotrexate
+ allogeneic bone marrow transplantation
Hematologic Diseases+6
+ Hemic and Lymphatic Diseases
+ Leukemia, Myeloid
Treatment Study
Summary
Study start date: February 1, 1999
Actual date on which the first participant was enrolled.OBJECTIVES: Determine the efficacy, in terms of overall survival and disease-free survival, and toxicity of cyclophosphamide and total body irradiation in patients with acute myeloid leukemia beyond first remission receiving HLA-matched related or unrelated hematopoietic stem cell transplantation. Determine the maximum tolerated dose (MTD) of iodine I 131 monoclonal antibody BC8 (I131 MOAB BC8) in these patients. Estimate the MTD of radiation delivered by I 131 MOAB BC8 to marrow of these patients and assess the effects on growth of marrow stroma in vitro. OUTLINE: This is radiation dose-escalation study. Patients are stratified according to available donor (related vs unrelated). Patients receive a biodistribution dose of iodine I 131 monoclonal antibody BC8 (I131 MOAB BC8) IV, then a therapeutic dose of I131 MOAB BC8 IV 6-14 days later (day -12). Patients undergo total body irradiation twice daily on days -6 to -4. Patients receive cyclophosphamide IV on days -3 and -2. Bone marrow cells (or peripheral blood stem cells) are infused on day 0. Patients with CNS leukemic involvement receive intrathecal methotrexate twice before the transplantation then every other week for 8 weeks beginning on day 32. These patients also receive cranial irradiation beginning on day 32. Cohorts of 4 patients each receive escalating doses of iodine I 131 attached to a standard dose of monoclonal antibody BC8 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the radiation dose preceding that at which 2 of up to 6 patients experience graft failure. Patients are followed at 6, 9, and 12 months, every 6 months for 1 year, and then annually thereafter. PROJECTED ACCRUAL: A total of 40 patients (20 per stratum) will be accrued for this study within 4 years.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.40 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.From 2 to 55 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
DISEASE CHARACTERISTICS: Diagnosis of 1 of the following: Acute myeloid leukemia (AML) beyond first remission OR with primary refractory disease AML that has transformed from myelodysplastic syndromes, if induction chemotherapy not recommended Documented CD45 expression in patients with relapsed disease Not needed for patients in remission Circulating blast count less than 10,000/mm^3 (may be controlled with hydroxyurea or similar agent) PATIENT CHARACTERISTICS: Age 2 to 55 Performance status Not specified Life expectancy More than 60 days Hematopoietic See Disease Characteristics Hepatic Bilirubin less than 1.5 mg/dL (unless bilirubin is determined by the gastroenterology service to be predominantly unconjugated [indirect] as the result of possible hemolysis) AST less than 1.5 times upper limit of normal (ULN) Renal Creatinine less than 2.0 mg/dL OR less than 1.5 times ULN for age Other Not pregnant or nursing Fertile patients must use effective contraception No major infection No circulating antibodies to mouse immunoglobulins HIV negative Able to tolerate diagnostic or therapeutic procedures (e.g., radiation isolation) PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics Endocrine therapy Not specified Radiotherapy No radiotherapy to maximum tolerated levels to any normal organ Surgery Not specified
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
Fred Hutchinson Cancer Research Center
Seattle, United StatesOpen Fred Hutchinson Cancer Research Center in Google Maps