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

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00005940
• Other study ID #: 1470.00
• Secondary ID: NCI-2013-01361FH
• Status: Completed
• Phase: Phase 2
• First received: July 5, 2000
• Last updated: August 28, 2017
• Start date: October 1999

Study information

• Verified date: August 2017
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 that has decreased or disappeared, but the cancer may still be in the body. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. primary completion date: January 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• 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)
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Radiation:
• iodine I 131 monoclonal antibody BC8
Given IV

Drug:
• busulfan
Given PO
• cyclophosphamide
Given IV

Procedure:
• allogeneic bone marrow transplantation
Undergo allogeneic PBSC or bone marrow transplant
• allogeneic hematopoietic stem cell transplantation
Undergo allogeneic PBSC or bone marrow transplant
• peripheral blood stem cell transplantation
Undergo allogeneic PBSC or bone marrow transplant

Drug:
• cyclosporine
Given IV or PO
• methotrexate
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Pacific Northwest National Laboratory	Richland	Washington
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington
United States	VA Puget Sound Health Care System	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival (DFS)	Summarized using appropriate time-to-event methods with estimates of the corresponding confidence intervals provided.	Up to 6 years
Secondary	Overall survival (OS)	Summarized using appropriate time-to-event methods with estimates of the corresponding confidence intervals provided.	Up to 6 years
Secondary	Relapse of AML patients	Summarized using appropriate time-to-event methods with estimates of the corresponding confidence intervals provided.	Up to 6 years
Secondary	Transplant-related mortality	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.	Up to 6 years