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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00003870
First received: November 1, 1999
Last updated: March 31, 2010
Last verified: March 2010
  Purpose

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.


Condition Intervention Phase
Leukemia
Drug: cyclophosphamide
Drug: methotrexate
Procedure: allogeneic bone marrow transplantation
Radiation: iodine I 131 monoclonal antibody BC8
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: 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 Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Estimated Enrollment: 40
Study Start Date: February 1999
Study Completion Date: November 2001
Primary Completion Date: November 2001 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   2 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003870

Locations
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
University of Washington Medical Center
Seattle, Washington, United States, 98195-6043
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Study Chair: Dana Christine Matthews, MD Fred Hutchinson Cancer Research Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00003870     History of Changes
Other Study ID Numbers: 1298.00, FHCRC-1298.00, NCI-H99-0029, CDR0000067034
Study First Received: November 1, 1999
Last Updated: March 31, 2010
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Fred Hutchinson Cancer Research Center:
recurrent childhood acute lymphoblastic leukemia
recurrent adult acute lymphoblastic leukemia
adult acute lymphoblastic leukemia in remission
childhood acute lymphoblastic leukemia in remission

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Cyclophosphamide
Methotrexate
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on July 31, 2014