Clinical Trial: Radiolabeled Monoclonal Antibody Therapy Combined With Total-body Irradiation, Allogeneic Peripheral Stem Cell Transplantation, and Immunosuppression Therapy in Treating Older Patients Who Have Advanced Acute Myeloid Leukemia, Myelodysplastic Syndrome, or

This study is currently recruiting patients.

Sponsors and Collaborators: Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)

Purpose

RATIONALE: Monoclonal antibodies can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by radiation therapy used to kill cancer cells. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Treatment with cyclosporine may prevent this from happening.

PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody therapy combined with total-body irradiation, allogeneic peripheral stem cell transplantation, and immunosuppression therapy in treating older patients who have advanced acute myeloid leukemia, myelodysplastic syndrome, or chronic myelomonocytic leukemia.

Condition Treatment or Intervention Phase
adult acute myeloid leukemia
atypical chronic myeloid leukemia
Chronic Myelomonocytic Leukemia
Graft Versus Host Disease
Myelodysplastic Syndromes
 Drug: allogeneic lymphocytes
 Drug: cyclosporine
 Drug: fludarabine
 Drug: iodine I 131 monoclonal antibody BC8
 Drug: mycophenolate mofetil
 Procedure: antibody therapy
 Procedure: biological response modifier therapy
 Procedure: bone marrow ablation with stem cell support
 Procedure: graft versus host disease prophylaxis/therapy
 Procedure: graft versus tumor induction
 Procedure: isotope therapy
 Procedure: leukocyte therapy
 Procedure: monoclonal antibody therapy
 Procedure: peripheral blood lymphocyte therapy
 Procedure: peripheral blood stem cell transplantation
 Procedure: radiation therapy
 Procedure: radioimmunotherapy
 Procedure: supportive care/therapy
Phase I

MedlinePlus related topics:  Bone Marrow Diseases;   Immune System and Disorders;   Leukemia, Adult Acute;   Leukemia, Adult Chronic;   Leukemia, Childhood;   Lymphatic Diseases

Study Type: Interventional
Study Design: Treatment

Official Title: Phase I Study of Iodine I 131 Monoclonal Antibody BC8 With Low-Dose Total Body Irradiation, Allogeneic Peripheral Blood Stem Cell Infusion, and Immunosuppression With Cyclosporine and Mycophenolate Mofetil in Elderly Patients With Advanced Acute Myeloid Leukemia, High-Risk Myelodysplastic Syndromes, or Chronic Myelomonocytic Leukemia

Further Study Details: 

OBJECTIVES:

OUTLINE: This is a dose-escalation study of iodine I 131 monoclonal antibody BC8.

  • Patients receive a test dose of iodine I 131 monoclonal antibody BC8 (
  • I MOAB BC8) IV followed 6-14 days later by a therapeutic dose of
  • I MOAB BC8 IV on day -12. Cohorts of up to 6 patients receive escalating doses of radiation via ^131I MOAB BC8 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 patients experience graft failure.
  • Total body irradiation (TBI) and allogeneic peripheral blood stem cell transplantation (PBSC): Patients receive low-dose TBI over 30-40 minutes followed by allogeneic PBSC transplantation on day 0. Patients with unrelated donors also receive fludarabine IV on days -4 to -2.
  • Immunosuppression therapy: All patients receive immunosuppression therapy with oral cyclosporine twice daily on days -3 to 56 with a taper through day 80 (for patients with a sibling donor), or days -3 to 100 with a taper through day 177 (for patients with an unrelated donor). Patients also receive mycophenolate mofetil orally or IV twice daily on days 0-27 with no taper (for patients with a sibling donor) or days 0-40 with a taper through day 96 (for patients with an unrelated donor).
  • Donor lymphocyte infusion (DLI): After completion of immunosuppression therapy, patients with stable mixed or full chimerism with no graft-versus-host disease (GVHD) receive DLI over 30 minutes. Treatment repeats every 28-65 days for up to 3 infusions in both patients with a sibling donor and those with an unrelated donor. Patients are followed weekly for 3 months, at 6, 9, and 12 months, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 25-30 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:  50 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of one of the following:
  • Advanced acute myeloid leukemia
  • Beyond first remission OR primary refractory disease
  • Myelodysplastic syndromes expressed as one of the following:
  • Refractory anemia with excess blasts (RAEB)
  • RAEB in transformation
  • Chronic myelomonocytic leukemia
  • Patients in relapse must have documented CD45 expression by myelodysplastic or leukemic cells
  • Circulating blast count < 10,000/mm^3 (control with hydroxyurea or similar agent allowed)
  • HLA-identical sibling donor or HLA-matched unrelated donor

PATIENT CHARACTERISTICS: Age

  • 50 and over

Performance status

  • ECOG 0-2 OR
  • Karnofsky 70-100%

Life expectancy

  • More than 60 days

Hematopoietic

  • See Disease Characteristics

Hepatic

  • Bilirubin < 2 times upper limit of normal (ULN)
  • AST and ALT < 2 times ULN
  • No evidence of hepatitis

Renal

  • Creatinine clearance > 50 mL/min

Cardiovascular

Other

  • No active infection
  • HIV negative
  • No perceived inability to tolerate diagnostic or therapeutic procedures, particularly in radiation isolation
  • No circulating antibody against mouse immunoglobulin
  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy

Chemotherapy

  • See Disease Characteristics

Endocrine therapy

  • Not specified

Radiotherapy

Surgery

  • Not specified

Other

  • No concurrent cardiac medications for antiarrhythmic or inotropic effects

Location and Contact Information


Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States; Recruiting
John Pagel, MD, PhD  206-667-1868 

Study chairs or principal investigators

John Pagel, MD, PhD,  Study Chair,  Fred Hutchinson Cancer Research Center   

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Study ID Numbers:  CDR0000068385; FHCRC-1432.00; NCI-H00-0066; NCT00008177
Record last reviewed:  July 2004
Last Updated:  December 6, 2004
Record first received:  January 6, 2001
ClinicalTrials.gov Identifier:  NCT00008177
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005