Radiolabeled BC8 Antibody, Busulfan, Cyclophosphamide Followed by Donor Stem Cell Transplant in Treating Patients With Acute Myelogenous Leukemia in First Remission

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00005940
First received: July 5, 2000
Last updated: August 13, 2014
Last verified: August 2014
  Purpose

This phase II trial studies how well iodine I 131 monoclonal antibody BC8, busulfan, and cyclophosphamide followed by donor stem cell transplant works in treating patients with acute myeloid leukemia in first remission. Giving chemotherapy drugs, such as busulfan and cyclophosphamide before a donor peripheral blood stem cell transplant helps stop the growth of cancer or abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. Also, radiolabeled monoclonal antibodies, such as iodine I 131 monoclonal antibody BC8, can find cancer cells and carry cancer-killing substances to them without harming normal cells. When the stem cells from a related donor, that closely matches the patient's blood, are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.


Condition Intervention Phase
Adult Acute Myeloid Leukemia in Remission
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Radiation: iodine I 131 monoclonal antibody BC8
Drug: busulfan
Drug: cyclophosphamide
Procedure: allogeneic bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Drug: cyclosporine
Drug: methotrexate
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Radiolabeled BC8 (Anti-CD45) Antibody Combined With Busulfan and Cyclophosphamide as Treatment for Acute Myelogenous Leukemia in First Remission Followed by HLA-Identical Related Peripheral Blood Stem Cell Transplantation

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Disease-free survival (DFS) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Summarized using appropriate time-to-event methods with estimates of the corresponding confidence intervals provided.


Secondary Outcome Measures:
  • Overall survival (OS) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Summarized using appropriate time-to-event methods with estimates of the corresponding confidence intervals provided.

  • Relapse of AML patients [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Summarized using appropriate time-to-event methods with estimates of the corresponding confidence intervals provided.

  • Transplant-related mortality [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
    Transplant-related toxicities are graded using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 2. Summarized using appropriate time-to-event methods with estimates of the corresponding confidence intervals provided.


Estimated Enrollment: 60
Study Start Date: October 1999
Primary Completion Date: January 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (radiolabeled BC8, chemotherapy, PBSCT)

RADIOLABELED ANTIBODY: Patients receive iodine I 131 monoclonal antibody BC8 IV on day -13.

CHEMOTHERAPY: Patients receive busulfan PO every 6 hours on days -7 to -4 and cyclophosphamide IV on days -3 and -2.

TRANSPLANT: Patients undergo allogeneic PBSC or BM transplant on day 0.

GRAFT-VS-HOST DISEASE PREVENTION: Patients receive cyclosporine IV or PO every 12 hours on days -1 to 50 with a taper to day 180. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

Radiation: iodine I 131 monoclonal antibody BC8
Given IV
Other Names:
  • I 131 MOAB BC8
  • I 131 Monoclonal Antibody BC8
  • iodine I 131 MOAB BC8
Drug: busulfan
Given PO
Other Names:
  • BSF
  • BU
  • Misulfan
  • Mitosan
  • Myeloleukon
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Procedure: allogeneic bone marrow transplantation
Undergo allogeneic PBSC or bone marrow transplant
Other Names:
  • bone marrow therapy, allogeneic
  • bone marrow therapy, allogenic
  • transplantation, allogeneic bone marrow
  • transplantation, allogenic bone marrow
Procedure: peripheral blood stem cell transplantation
Undergo autologous PBSC or bone marrow transplant
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Drug: cyclosporine
Given IV or PO
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Drug: methotrexate
Given IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the efficacy (as measured by survival and disease-free survival) and toxicity of a regimen of busulfan 16 mg/kg and cyclophosphamide 120 mg/kg plus 131I-labeled anti-cluster of differentiation (CD) 45 antibody (iodine I 131 monoclonal antibody BC8) (delivering a dose of 5.25 gray [Gy] to the normal organ receiving the highest dose) in patients with acute myeloid leukemia (AML) in first remission receiving human leukocyte antigen (HLA)-identical related peripheral blood stem cell (PBSC) transplants.

OUTLINE:

RADIOLABELED ANTIBODY: Patients receive iodine I 131 monoclonal antibody BC8 intravenously (IV) on day -13.

CHEMOTHERAPY: Patients receive busulfan orally (PO) every 6 hours on days -7 to -4 and cyclophosphamide IV on days -3 and -2.

TRANSPLANT: Patients undergo allogeneic PBSC or bone marrow (BM) transplant on day 0.

GRAFT-VS-HOST DISEASE PREVENTION: Patients receive cyclosporine IV or PO every 12 hours on days -1 to 50 with a taper to day 180. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

After completion of study treatment, patients are followed up at 6, 9, and 12 months, every 6 months for 1 year and then yearly thereafter.

  Eligibility

Ages Eligible for Study:   16 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with AML in first remission
  • Creatinine < 2.0 mg/dl
  • Bilirubin < 1.5 mg/dl which is expected to exclude patients at high risk of developing veno-occlusive disease of the liver
  • Aspartate aminotransferase (AST) < 1.5 times the upper limit of normal which is expected to exclude patients at high risk of developing veno-occlusive disease of the liver
  • Patients must have an expected survival of > 60 days and must be free of major infection
  • DONOR: genotypic or phenotypic HLA-matched family members; related donors should be matched by molecular methods at the intermediate resolution level at HLA-A, B, C, and DR beta 1 (DRB1) according to Fred Hutchinson Cancer Research Center (FHCRC) Standard Practice Guidelines and to the allele level at DQ beta 1 (DQB1)

Exclusion Criteria:

  • Patients with history of or current leukemic involvement of the central nervous system (CNS)
  • Prior radiation to maximally tolerated levels to any normal organ
  • Inability to understand or give an informed consent
  • Patients who are seropositive for human immunodeficiency virus (HIV)
  • Perceived inability to tolerate diagnostic or therapeutic procedures, particularly treatment in radiation isolation
  • Circulating antibody against mouse immunoglobulin
  • DONOR: unrelated donors and donors mismatched for 1 or more HLA antigens
  • DONOR: donors who for psychologic, physiologic or medical reasons are unable to undergo filgrastim (G-CSF)- mobilized PBSC collection or marrow harvesting
  • DONOR: donors who are seropositive for HIV
  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: NCT00005940

Locations
United States, Washington
Pacific Northwest National Laboratory
Richland, Washington, United States, 99352
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
VA Puget Sound Health Care System
Seattle, Washington, United States, 98101
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: John Pagel Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00005940     History of Changes
Other Study ID Numbers: 1470.00, NCI-2013-01361, FHCRC-1470.00, NCI-H00-0056, CDR0000067778, P30CA015704, P01CA044991
Study First Received: July 5, 2000
Last Updated: August 13, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia
Neoplasms by Histologic Type
Neoplasms
Cyclophosphamide
Cyclosporins
Cyclosporine
Methotrexate
Busulfan
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Iodine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Enzyme Inhibitors
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Abortifacient Agents, Nonsteroidal

ClinicalTrials.gov processed this record on September 22, 2014