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

Fred Hutchinson Cancer Center (FHCC)

Status and phase

Completed

Phase 2

Conditions

Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities

Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)

Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)

Adult Acute Myeloid Leukemia in Remission

Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)

Adult Acute Myeloid Leukemia With Del(5q)

Treatments

Drug: cyclophosphamide

Procedure: peripheral blood stem cell transplantation

Drug: busulfan

Radiation: iodine I 131 monoclonal antibody BC8

Other: laboratory biomarker analysis

Procedure: allogeneic bone marrow transplantation

Procedure: allogeneic hematopoietic stem cell transplantation

Drug: cyclosporine

Drug: methotrexate

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00005940

CDR0000067778

NCI-2013-01361 (Registry Identifier)

NCI-H00-0056

1470

P01CA044991 (U.S. NIH Grant/Contract)

1470.00 (Other Identifier)

P30CA015704 (U.S. NIH Grant/Contract)

FHCRC-1470.00

Details and patient eligibility

About

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.

Full 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.

Enrollment

18 patients

Sex

All

Ages

16 to 55 years old

Volunteers

No 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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

18 participants in 1 patient group

Treatment (radiolabeled BC8, chemotherapy, PBSCT)

Experimental group

Description:

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.

Treatment: