Iodine I 131 Monoclonal Antibody BC8, Fludarabine, Total-Body Irradiation, and Donor Stem Cell Transplant Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndromes - Full Text View

Sponsored by:	Fred Hutchinson Cancer Research Center
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00119366

Purpose

RATIONALE: Giving chemotherapy drugs, such as fludarabine, and total-body irradiation 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 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 fludarabine and total-body irradiation before the transplant together with cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. Giving a radiolabeled monoclonal antibody together with donor stem cell transplant, cyclosporine, and mycophenolate mofetil may be an effective treatment for advanced acute myeloid leukemia or myelodysplastic syndromes.

PURPOSE: This phase I/II trial is studying the side effects and best dose of iodine I 131 monoclonal antibody BC8 when given together with fludarabine, total-body irradiation, and donor stem cell transplant followed by cyclosporine and mycophenolate mofetil in treating patients for advanced acute myeloid leukemia or myelodysplastic syndromes.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndromes	Drug: cyclosporine Drug: fludarabine phosphate Drug: mycophenolate mofetil Procedure: peripheral blood stem cell transplantation Radiation: iodine I 131 monoclonal antibody BC8 Radiation: radiation therapy	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Feasibility Trial Combining Radiolabeled BC8 (Anti-CD45) Antibody With Fludarabine and Low Dose TBI Followed by Related or Unrelated PBSC Infusion and Post-Transplant Immunosuppression for Patients With Advanced AML or High Risk Myelodysplastic Syndrome

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Radiation Therapy

Drug Information available for: Fludarabine Cyclosporine Fludarabine monophosphate Cyclosporin Cadexomer iodine Mycophenolate mofetil hydrochloride Mycophenolate Mofetil Immunoglobulins Iodine Sodium iodide I 131 Globulin, Immune

U.S. FDA Resources

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 ]
Nonmortal toxicity [ Designated as safety issue: Yes ]
Level of donor chimerism [ Designated as safety issue: No ]
Remission achievement and duration [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	May 2003
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose and toxicity of iodine I 131 monoclonal antibody BC8 (^131I MOAB BC8) when administered with fludarabine and low-dose total body irradiation followed by allogeneic peripheral blood stem cell transplantation and immunosuppression comprising cyclosporine and mycophenolate mofetil in patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndromes.
Determine the transplant-related mortality of patients treated with this regimen.
Determine the rate of donor chimerism in patients treated with this regimen.
Correlate the level of donor chimerism with the estimated radiation dose delivered to hematopoietic tissue by
- 131I MOAB BC8 in patients treated with this regimen.
Determine, preliminarily, the rates of disease relapse, graft-versus-host disease, and 2-year disease-free survival in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of therapeutic dose iodine I 131 monoclonal antibody BC8 (^131I MOAB BC8).

Radioimmunotherapy: Patients receive a biodistribution dose of ^131I MOAB BC8 IV on approximately day -21 or
- 20. Patients then undergo gamma camera scanning over approximately 3 days. Patients then receive a therapeutic dose of ^131I MOAB BC8 IV on approximately day -14. Cohorts of 1-4 patients receive escalating therapeutic doses of ^131I MOAB BC8 until the maximum tolerated dose is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience graft failure.
Conditioning regimen: Patients receive fludarabine IV on days -4 to -2 and undergo low-dose total body irradiation (TBI) on day 0.
Allogeneic peripheral blood stem cell transplantation (PBSCT): After completion of TBI, patients undergo allogeneic PBSCT on day 0.
Immunosuppression: Patients with a matched sibling donor receive oral cyclosporine twice daily on days -3 to 56 followed by a taper to day 80 in the absence of graft-versus-host disease. These patients also receive oral mycophenolate mofetil 3 times daily beginning 4-6 hours after PBSCT and continuing until day 27. Patients with a matched unrelated donor receive oral cyclosporine twice daily on days -3 to 100 followed by a taper to day 177.

These patients also receive oral mycophenolate mofetil 3 times daily beginning 4-6 hours after PBSCT and continuing until day 40 followed by a taper to day 96. Treatment continues in the absence of unacceptable toxicity or development of anti-mouse antibodies.

After completion of study treatment, patients are followed at 6, 9, 12, 18, and 24 months and then annually thereafter.

PROJECTED ACCRUAL: A total of 25-30 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	16 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following diseases
- Myelodysplastic syndromes (MDS), expressed as 1 of the following:
  - Refractory anemia with excess blasts (RAEB)
  - RAEB in transformation (RAEBT)
  - Refractory cytopenia with multilineage dysplasia (RCMD)
  - RCMD with ringed sideroblasts (RCMD-RS)
  - Chronic myelomonocytic leukemia (CMML)
- Advanced acute myeloid leukemia beyond first remission, primary refractory disease, OR evolved from MDS or myeloproliferative disorders
  - Meets 1 of the following criteria:
    - Not in first remission AND has CD45-expressing leukemic blasts
      - Circulating blast count < 10,000/mm^3 (may be controlled with hydroxyurea or similar agents)
    - In remission
      - Previously documented CD45-negative disease allowed
      - Phenotyping is not required
Peripheral blood stem cell donor available, meeting 1 of the following criteria:
- HLA-matched identical sibling donor
  - Matched for HLA-A, -B, -C, and -DRB1 at the intermediate resolution level and for -DQB1 at the allele level by molecular methods
- HLA-matched unrelated donor
  - Matched for HLA-A, -B, -C, -DRB1, and -DQB1 at the allele level
    - One allele mismatch allowed for HLA-A, -B, or -C

PATIENT CHARACTERISTICS:

Age

16 to 50

Performance status

Karnofsky 70-100% OR
ECOG 0-2

Life expectancy

More than 60 days

Hematopoietic

See Disease Characteristics

Hepatic

Bilirubin < 2 times upper limit of normal (ULN)
AST and ALT < 2 times ULN

Renal

Creatinine clearance > 50 mL/min

Cardiovascular

No symptomatic coronary artery disease

Other

Not pregnant or nursing
Fertile patients must use effective contraception
HIV negative
Able to tolerate diagnostic or therapeutic procedures, particularly treatment in radiation isolation
No circulating antibody against mouse immunoglobulin
No active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

No prior autologous or allogeneic hematopoietic stem cell transplantation

Chemotherapy

See Disease Characteristics

Endocrine therapy

Not specified

Radiotherapy

No prior radiotherapy at a maximum tolerated dose to any normal organ

Surgery

Not specified

Other

No concurrent cardiac medications for anti-arrhythmic or inotropic effects

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00119366

Locations

United States, Washington
Fred Hutchinson Cancer Research Center	Recruiting
Seattle, Washington, United States, 98109-1024
Contact: John Pagel, MD, PhD 206-667-1868
Pacific Northwest National Laboratory	Recruiting
Richland, Washington, United States, 99352
Contact: D.R. Fisher, PhD 888-375-7665
Seattle Cancer Care Alliance	Recruiting
Seattle, Washington, United States, 98109-1023
Contact: Clinical Trials Office - Seattle Cancer Care Alliance 800-804-8824
Veterans Affairs Medical Center - Seattle	Recruiting
Seattle, Washington, United States, 98108
Contact: Thomas R. Chauncey, MD, PhD 206-764-2199

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

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

Responsible Party:	Fred Hutchinson Cancer Research Center ( John Pagel )
Study ID Numbers:	CDR0000430691, FHCRC-1809.00
Study First Received:	July 12, 2005
Last Updated:	July 7, 2009
ClinicalTrials.gov Identifier:	NCT00119366 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

adult acute myeloid leukemia in remission
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)
recurrent adult acute myeloid leukemia

childhood acute myeloid leukemia in remission
recurrent childhood acute myeloid leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
childhood myelodysplastic syndromes

Study placed in the following topic categories:

Antimetabolites
Anti-Infective Agents
Cyclosporine
Precancerous Conditions
Immunologic Factors
Mycophenolic Acid
Leukemia, Myeloid, Acute
Cyclosporins
Antibodies, Monoclonal
Anti-Bacterial Agents
Leukemia
Acute Myelocytic Leukemia
Preleukemia
Acute Myeloid Leukemia, Adult
Antifungal Agents

Neoplasm Metastasis
Mycophenolate mofetil
Iodine
Micronutrients
Congenital Abnormalities
Immunoglobulins
Hematologic Diseases
Myelodysplastic Syndromes
Trace Elements
Leukemia, Myeloid
Fludarabine monophosphate
Immunosuppressive Agents
Recurrence
Acute Myeloid Leukemia, Childhood
Anti-Infective Agents, Local

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Cyclosporine
Molecular Mechanisms of Pharmacological Action
Precancerous Conditions
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Mycophenolic Acid
Antibiotics, Antineoplastic
Leukemia, Myeloid, Acute
Cyclosporins
Antibodies, Monoclonal
Leukemia

Preleukemia
Pathologic Processes
Therapeutic Uses
Antifungal Agents
Syndrome
Mycophenolate mofetil
Iodine
Micronutrients
Dermatologic Agents
Disease
Neoplasms by Histologic Type
Hematologic Diseases
Growth Substances
Myelodysplastic Syndromes
Trace Elements

ClinicalTrials.gov processed this record on September 09, 2009