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

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

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.

Study Overview

• Status: Completed
• Conditions: 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(16;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(15;17)(q22;q12)
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: cyclophosphamide; Drug: methotrexate; Radiation: iodine I 131 monoclonal antibody BC8; Drug: cyclosporine; Drug: busulfan; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Richland, Washington, United States, 99352
      • Pacific Northwest National Laboratory
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
    • Seattle, Washington, United States, 98101
      • VA Puget Sound Health Care System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 55 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

Other: laboratory biomarker analysis; Correlative studies; Drug: cyclophosphamide; Given IV; Other Names: Cytoxan; Endoxan; CPM; CTX; Endoxana; Drug: methotrexate; Given IV; Other Names: amethopterin; Folex; methylaminopterin; Mexate; MTX; 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: cyclosporine; Given IV or PO; Other Names: ciclosporin; cyclosporin; cyclosporin A; CYSP; Sandimmune; Drug: busulfan; Given PO; Other Names: BSF; BU; Misulfan; Mitosan; Myeloleukon; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival (DFS)	Summarized using appropriate time-to-event methods with estimates of the corresponding confidence intervals provided.	Up to 6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Summarized using appropriate time-to-event methods with estimates of the corresponding confidence intervals provided.	Up to 6 years
Relapse of AML patients	Summarized using appropriate time-to-event methods with estimates of the corresponding confidence intervals provided.	Up to 6 years
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

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Johnnie Orozco, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start: October 1, 1999
• Primary Completion (Actual): January 1, 2006

Study Registration Dates

• First Submitted: July 5, 2000
• First Submitted That Met QC Criteria: July 8, 2003
• First Posted (Estimate): July 9, 2003

Study Record Updates

• Last Update Posted (Actual): August 30, 2017
• Last Update Submitted That Met QC Criteria: August 28, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents, Local; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Dermatologic Agents; Trace Elements; Micronutrients; Antifungal Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Calcineurin Inhibitors; Cyclophosphamide; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Iodine; Antineoplastic Agents, Immunological; Methotrexate; Busulfan; Cyclosporine; Cyclosporins
• Other Study ID Numbers: 1470.00 (Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium); P01CA044991 (U.S. NIH Grant/Contract); P30CA015704 (U.S. NIH Grant/Contract); NCI-2013-01361 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); FHCRC-1470.00; NCI-H00-0056; 1470; CDR0000067778