Iodine I 131 Monoclonal Antibody BC8, Chemotherapy, Total-Body Irradiation, and a Donor Bone Marrow Transplant in Treating Patients With Advanced Acute Leukemia or High-Risk Myelodysplastic Syndromes - Full Text View

Sponsors and Collaborators:	Fred Hutchinson Cancer Research Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00589316

Purpose

RATIONALE: Giving chemotherapy and total-body irradiation before a donor bone marrow transplant helps stop the growth of cancer cells. It also 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 either kill them or deliver cancer-killing substances to them without harming normal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclophosphamide, tacrolimus, and mycophenolate mofetil after the transplant may stop this from happening.

PURPOSE: This phase I trial is studying the side effects and best dose of iodine I 131 monoclonal antibody BC8 when given together with fludarabine, cyclophosphamide, and total-body irradiation before donor bone marrow transplant and cyclophosphamide, tacrolimus, and mycophenolate mofetil in treating patients with advanced acute myeloid leukemia or acute lymphoblastic leukemia or high-risk myelodysplastic syndromes.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndromes	Biological: filgrastim Drug: cyclophosphamide Drug: fludarabine phosphate Drug: mycophenolate mofetil Drug: tacrolimus Procedure: allogeneic bone marrow transplantation Radiation: iodine I 131 monoclonal antibody BC8 Radiation: total-body irradiation	Phase I

MedlinePlus related topics: Bone Marrow Transplantation Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Radiation Therapy

Drug Information available for: Cyclophosphamide Fludarabine Fludarabine monophosphate Cadexomer iodine Tacrolimus anhydrous Tacrolimus Mycophenolate mofetil hydrochloride Filgrastim Mycophenolate Mofetil Immunoglobulins Iodine Sodium iodide I 131 Globulin, Immune

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Hematopoietic Bone Marrow Transplantation for Patients With High-Risk Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), or Myelodysplastic Syndrome (MDS) Using Related HLA-Mismatched Donors: A Trial Using Radiolabeled Anti-CD45 Antibody Combined With Immunosuppression Before and After Transplantation

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose of iodine I 131 monoclonal antibody BC8 [ Designated as safety issue: Yes ]
Incidence of dose-limiting toxicities within the first 100 days after transplant [ Designated as safety issue: Yes ]
Rate of nonrelapse-related mortality [ Designated as safety issue: No ]
Rate of engraftment [ Designated as safety issue: No ]
Rate of donor chimerism [ Designated as safety issue: No ]
Incidence of acute graft-versus-host disease within the first 100 days after transplant [ Designated as safety issue: No ]
Achievement and duration of remission [ Designated as safety issue: No ]

Secondary Outcome Measures:

Rate of immune reconstitution [ Designated as safety issue: No ]
Disease-free survival at 100 days [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	September 2007
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To determine the maximum tolerated dose of radiation delivered via iodine I 131 monoclonal antibody BC8 when combined with conditioning comprising fludarabine phosphate, cyclophosphamide, and total-body irradiation followed by haploidentical related allogeneic bone marrow transplantation and post-transplant immunosuppression comprising cyclophosphamide, tacrolimus, and mycophenolate mofetil in patients with advanced acute myeloid leukemia or acute lymphoblastic leukemia or high-risk myelodysplastic syndromes.

Secondary

To estimate rates of immune reconstitution, engraftment, and donor chimerism in patients treated with this regimen.
To determine rates of disease relapse, acute graft-versus-host disease, and day 100 disease-free survival in patients treated with this regimen.

OUTLINE: This is a dose escalation study of iodine I 131 monoclonal antibody BC8 followed by a phase II study.

Radioimmunotherapy: Patients receive therapeutic iodine I 131 monoclonal antibody BC8 IV on day -14.
Conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1-2 hours on days -6 and -5. Patients undergo total-body irradiation on day -1.
Allogeneic bone marrow transplantation (BMT): Patients undergo allogeneic BMT on day 0.
Post-transplantation immunosuppression: Patients receive cyclophosphamide IV over 1-2 hours on day 3, mycophenolate mofetil IV or orally three times daily on days 4-35, and tacrolimus IV over 1-2 hours or orally on days 4-180.
Growth factor support: Patients receive filgrastim (G-CSF) IV or subcutaneously beginning on day 4 and continuing until blood counts recover.

After completion of study therapy, patients are followed periodically.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of one of the following:
- Advanced acute myeloid leukemia or acute lymphoblastic leukemia meeting one of the following criteria:
  - Beyond first remission
  - Primary refractory disease
  - Evolved from myelodysplastic syndromes (MDS) or myeloproliferative disorders
- High-risk MDS, including any of the following:
  - Refractory anemia with excess blasts
  - Refractory cytopenia with multilineage dysplasia (RCMD)
  - RCMD with ringed sideroblasts
  - Chronic myelomonocytic leukemia
Patients not in remission must have CD45-expressing leukemic blasts
- Patients in remission do not require phenotyping and may have leukemia previously documented to be CD45 negative
Circulating blast count < 10,000/mm^3 (hydroxyurea or similar agent is allowed to control blast count )
No CNS involvement with disease refractory to intrathecal chemotherapy and/or standard cranial spinal radiotherapy
Must have a related donor available, meeting the following criteria:
- Donor identical with patient for one HLA haplotype AND mismatched at the HLA-A, -B or DRB1 loci of the unshared haplotype (with the exception of single HLA-A, -B or DRB1 mismatches)
- Patient is not cross-match positive with donor

PATIENT CHARACTERISTICS:

Karnofsky performance status (PS) 70-100% OR ECOG PS 0-2
Life expectancy > 60 days
Creatinine clearance > 50 mL/min
Bilirubin < 2 times upper limit of normal (ULN)
AST and ALT < 2 times ULN
Left ventricular ejection fraction ≥ 35%
Corrected DLCO ≥ 35%
No requirement for supplemental continuous oxygen
No HIV seropositivity
No active infection
No circulating antibody against mouse immunoglobulin (HAMA)
No symptomatic coronary artery disease
No liver abnormalities, including any of the following:
- Fulminant liver failure
- Cirrhosis of the liver with evidence of portal hypertension
- Alcoholic hepatitis
- Esophageal varices
- Hepatic encephalopathy
- Uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time
- Ascites related to portal hypertension
- Bacterial or fungal liver abscess
- Biliary obstruction
- Chronic viral hepatitis
- Symptomatic biliary disease
Able to tolerate diagnostic or therapeutic procedures, particularly treatment in radiation isolation
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 12 months after transplant

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior radiotherapy at maximally tolerated levels to any critical normal organ
No concurrent cardiac medications for anti-arrhythmic or inotropic effects

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00589316

Locations

United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Recruiting
Seattle, Washington, United States, 98109-1024
Contact: Clinical Trials Office - Fred Hutchinson Cancer Research Cente 800-804-8824
Seattle Cancer Care Alliance	Recruiting
Seattle, Washington, United States, 98109-1023
Contact: Clinical Trials Office - Seattle Cancer Care Alliance 800-804-8824

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

John Pagel, MD, PhD

Fred Hutchinson Cancer Research Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000579350, FHCRC-2186.00
Study First Received:	January 3, 2008
Last Updated:	April 1, 2009
ClinicalTrials.gov Identifier:	NCT00589316 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
refractory anemia with excess blasts
refractory cytopenia with multilineage dysplasia
chronic myelomonocytic leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
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)
secondary acute myeloid leukemia
adult acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes

Study placed in the following topic categories:

Antimetabolites
Chronic Myelomonocytic Leukemia
Leukemia, Lymphoid
Immunologic Factors
Precancerous Conditions
Tacrolimus
Cyclophosphamide
Leukemia, Myeloid, Acute
Refractory Anemia
Antibodies, Monoclonal
Leukemia
Preleukemia
Acute Myelocytic Leukemia
Anemia, Refractory
Acute Myeloid Leukemia, Adult

Mycophenolate mofetil
Neoplasm Metastasis
Iodine
Micronutrients
Congenital Abnormalities
Alkylating Agents
Lymphoma
Acute Lymphoblastic Leukemia
Immunoglobulins
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Hematologic Diseases
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Anemia

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Leukemia, Lymphoid
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Precancerous Conditions
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide
Tacrolimus
Leukemia, Myeloid, Acute
Antibodies, Monoclonal
Leukemia
Preleukemia

Pathologic Processes
Therapeutic Uses
Syndrome
Mycophenolate mofetil
Iodine
Micronutrients
Alkylating Agents
Immunoproliferative Disorders
Neoplasms by Histologic Type
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Disease
Immune System Diseases
Hematologic Diseases
Growth Substances
Myelodysplastic Syndromes

ClinicalTrials.gov processed this record on May 07, 2009