Monoclonal Antibody Therapy, Cyclophosphamide, and Total-Body Irradiation Followed by Peripheral Stem Cell Transplantation in Treating Patients With Advanced Recurrent Acute Lymphocytic Leukemia

NCT ID: NCT00003870

Last Updated: 2010-04-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-02-28
• Study Completion Date: 2001-11-30

Brief Summary

RATIONALE: Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill cancer cells.

PURPOSE: Phase II trial to study the effectiveness of monoclonal antibody therapy, cyclophosphamide, and total-body irradiation followed by peripheral stem cell transplantation in treating patients who have advanced recurrent acute lymphocytic leukemia.

Detailed Description

OBJECTIVES: I. Assess the efficacy and toxicity of iodine I 131 monoclonal antibody BC8, cyclophosphamide, and total body irradiation in patients with advanced acute lymphocytic leukemia who are receiving HLA matched related or unrelated bone marrow transplantation. II. Determine the maximum tolerated dose (MTD) of iodine I 131 monoclonal antibody BC8 in these patients. III. Estimate the MTD of radiation delivered by iodine I 131 monoclonal antibody BC8 to the marrow. IV. Study the influence of marrow cellularity, level of antigen expression by leukemic cells, and degree of antigen saturation by antibody on the biodistribution of iodine I 131 monoclonal antibody BC8 in these patients.

OUTLINE: This is a dose-escalation study. All patients receive a test dose of iodine I 131 monoclonal antibody BC8 (MOAB BC8) IV over several hours 6-14 days prior to the therapeutic dose. Patients receive the therapeutic dose of iodine I 131 MOAB BC8 IV over several hours on day -11, total body irradiation over 30-40 minutes twice a day on days -6 to -4, and cyclophosphamide IV over 1 hour on days -3 and -2. Patients undergo allogenic bone marrow transplantation on day 0. Patients receive intrathecal methotrexate twice prior to transplantation and then every other week for 4 weeks beginning on day 32 posttransplant. Cohorts of 4 patients receive escalating doses of iodine I 131 monoclonal antibody until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 4 patients experience dose-limiting toxicity. Patients are followed for the first 100 days, at 6, 9 and 12 months, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 4 years.

Conditions

Leukemia

Study Design

• Primary Study Purpose: TREATMENT

Interventions

cyclophosphamide

Intervention Type: DRUG

methotrexate

Intervention Type: DRUG

allogeneic bone marrow transplantation

Intervention Type: PROCEDURE

iodine I 131 monoclonal antibody BC8

Intervention Type: RADIATION

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically confirmed acute lymphocytic leukemia that is beyond first remission or is refractory Relapsed disease must be CD45 positive Patients in remission may be CD45 negative

PATIENT CHARACTERISTICS: Age: 2 to 55 Performance status: Not specified Life expectancy: More than 60 days Hematopoietic: Circulating blast count less than 10,000/mm3 (control with hydroxyurea or similar agent allowed) Hepatic: Bilirubin less than 1.5 mg/dL AST less than 1.5 times upper limit of normal (ULN) Must have no veno-occlusive liver disease Renal: Creatinine less than 2.0 mg/dL OR less than 1.5 times ULN for age Other: No active infection HIV negative No circulating antimouse immunoglobulin antibodies Must be able to tolerate diagnostic or therapeutic procedures (e.g., radiation isolation)

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to maximum tolerated levels to any normal organ Surgery: Not specified

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Principal Investigators

Dana Christine Matthews, MD

Role: STUDY_CHAIR

Fred Hutchinson Cancer Center

Locations

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

University of Washington Medical Center

Seattle, Washington, United States

Countries

United States

Other Identifiers

FHCRC-1298.00

Identifier Type: -

Identifier Source: secondary_id

NCI-H99-0029

Identifier Type: -

Identifier Source: secondary_id

CDR0000067034

Identifier Type: REGISTRY

Identifier Source: secondary_id

1298.00

Identifier Type: -

Identifier Source: org_study_id