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

Sponsor

Fred Hutchinson Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00005940

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

Patients Per Site

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	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: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Drug: cyclosporine Drug: methotrexate Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Oct 1, 1999

Actual Primary Completion Date :

Jan 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
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: allogeneic hematopoietic stem cell transplantation Undergo allogeneic PBSC or bone marrow transplant Procedure: peripheral blood stem cell transplantation Undergo allogeneic 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

Arm

Intervention/Treatment

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

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: allogeneic hematopoietic stem cell transplantation

Undergo allogeneic PBSC or bone marrow transplant

Procedure: peripheral blood stem cell transplantation

Undergo allogeneic 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

Outcome Measures

Primary Outcome Measures

Disease-free survival (DFS) [Up to 6 years]
Summarized using appropriate time-to-event methods with estimates of the corresponding confidence intervals provided.

Secondary Outcome Measures

Overall survival (OS) [Up to 6 years]
Summarized using appropriate time-to-event methods with estimates of the corresponding confidence intervals provided.
Relapse of AML patients [Up to 6 years]
Summarized using appropriate time-to-event methods with estimates of the corresponding confidence intervals provided.
Transplant-related mortality [Up to 6 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Pacific Northwest National Laboratory	Richland	Washington	United States	99352
2	VA Puget Sound Health Care System	Seattle	Washington	United States	98101
3	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109