Radiolabeled Monoclonal Antibody, Cyclophosphamide, and Total Body Irradiation Followed By Donor Stem Cell Transplantation in Treating Patients With Advanced Acute Myeloid Leukemia

August 20, 2010 updated by: Fred Hutchinson Cancer Center

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

RATIONALE: Radiolabeled monoclonal antibodies can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy work in 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. Donor stem cell transplantation may be able to replace immune cells that were destroyed by radiolabeled monoclonal antibody therapy, chemotherapy and radiation therapy.

PURPOSE: Phase II trial to study the effectiveness of combining radiolabeled monoclonal antibody with cyclophosphamide and total-body irradiation followed by donor stem cell transplantation in treating patients who have advanced acute myeloid leukemia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98109-1024
        • Fred Hutchinson Cancer Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 55 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fred Hutchinson Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Eneida Nemecek, MD, Fred Hutchinson Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 1999

Primary Completion (Actual)

March 1, 2005

Study Completion (Actual)

March 1, 2005

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

October 6, 2003

First Posted (Estimate)

October 7, 2003

Study Record Updates

Last Update Posted (Estimate)

August 24, 2010

Last Update Submitted That Met QC Criteria

August 20, 2010

Last Verified

August 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1297.00
  • FHCRC-1297.00
  • NCI-H99-0028
  • CDR0000067032 (Registry Identifier: PDQ)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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