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

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Trial phase: 
Phase I
Recruitment status: 
Active, not recruiting

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.

Background information
Trial ID: 
NCT00008177
Other unique IDs: 
CDR0000068385
FHCRC-1432.00
NCI-H00-0066
Official title: 

A Phase I Study Combining Escalating Doses of Radiolabeled BC8 (Anti-CD45) Antibody With Fludarabine, Low Dose TBI, PBSC Infusion And Post-Transplant Immunosuppression With Cyclosporine And Mycophenolate Mofetil to Establish Mixed or Full Donor Chimerism

Detailed description: 

OBJECTIVES:

  • Determine the maximum tolerated dose of radiation delivered via iodine I 131 monoclonal antibody BC8 when combined with nonmyeloablative low-dose total body irradiation and cyclosporine and mycophenolate mofetil in elderly patients with advanced acute myeloid leukemia, high-risk myelodysplastic syndromes, or chronic myelomonocytic leukemia who undergo allogeneic peripheral blood stem cell transplantation.
  • Determine the rates of donor chimerism in patients treated with this regimen.
  • Correlate level of donor chimerism with estimated radiation doses delivered to hematopoietic tissues via the monoclonal antibody in patients treated with this regimen.
  • Determine disease response and duration of remission in patients treated with this regimen.

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

  • Radioimmunotherapy: Patients receive a test dose of iodine I 131 monoclonal antibody BC8 (^131I MOAB BC8) IV followed 6-14 days later by a therapeutic dose of ^131I 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 75 patients will be accrued for this study.

Number to be enrolled: 
75 patients
Clinical information
Age groups: 
Adult
Senior
Gender: 
Both
Eligibility criteria: 

DISEASE CHARACTERISTICS:

  • Diagnosis of one of the following:
    • Advanced acute myeloid leukemia, meeting any of the following criteria:
      • Beyond first remission
      • Refractory disease
      • Evolved from myelodysplastic syndromes (MDS) or myeloproliferative syndromes
    • MDS expressed as one of the following:
      • Refractory anemia with excess blasts (RAEB)
      • RAEB in transformation
      • Refractory cytopenia with multilineage dysplasia (RCMD)
      • RCMD with ringed sideroblasts
    • 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
    • Matched related donor must be willing and able to undergo filgrastim (G-CSF)-mobilized peripheral blood stem cell pheresis

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

  • No symptomatic coronary artery disease

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

  • No prior bone marrow or peripheral blood stem cell transplantation

Chemotherapy

  • See Disease Characteristics

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radiotherapy to maximally tolerated levels of radiation to any normal organ

Surgery

  • Not specified

Other

  • No concurrent cardiac medications for antiarrhythmic or inotropic effects

Study design: 
Treatment
Interventions: 
peripheral blood stem cell transplantation
fludarabine phosphate
therapeutic allogeneic lymphocytes
cyclosporine
Mycophenolate mofetil
iodine I 131 monoclonal antibody BC8
Conditions treated: 
Leukemia
Myelodysplastic Syndromes
Graft Versus Host Disease
Outcome measurements: 

Maximum tolerated dose [ Designated as safety issue: Yes ]

Achievement and duration of remission [ Designated as safety issue: No ]

Level of donor chimerism and correlation with radiotherapy doses [ Designated as safety issue: No ]

Funding
Funding types: 
NIH
OTHER
Sponsor: 
National Cancer Institute (NCI)
Fred Hutchinson Cancer Research Center
Dates
Date the data was first received: 
Sat, 2001-01-06
Trial start date: 
Thu, 1999-07-01
Trial completion date: 
Wed, 1969-12-31
Trial last updated: 
Wed, 2009-05-20