Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 2 to 55 NCI FHCRC-1297.00 NCI-H99-0028, NCT00003868

Objectives

1. 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.
2. Determine the maximum tolerated dose (MTD) of iodine I 131 monoclonal antibody BC8 (I131 MOAB BC8) in these patients.
3. 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.

Entry 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/mm³ (may be controlled with hydroxyurea or similar agent)

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

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)

Expected Enrollment

A total of 40 patients (20 per stratum) will be accrued for this study within 4 years.

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.

Trial Contact Information

Trial Lead Organizations

Fred Hutchinson Cancer Research Center

Eneida Nemecek, MD, Protocol chair		Ph: 206-667-1816 Email: enemecek@fhcrc.org

Registry Information
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 Myeloid Leukemia and Myelodysplastic Syndrome
Trial Start Date		1999-02-17
Registered in ClinicalTrials.gov		NCT00003868
Date Submitted to PDQ		1999-04-22
Information Last Verified		2005-04-11
NCI Grant/Contract Number		CA15704, CA44991, CA100394

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