Cyclophosphamide, Antithymocyte Globulin, and Total-Body Irradiation in Treating Patients With Severe Aplastic Anemia Undergoing Umbilical Cord Blood Transplant - Full Text View

Sponsor:	Fred Hutchinson Cancer Research Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00354419

Purpose

RATIONALE: Giving chemotherapy and total-body irradiation before a donor umbilical cord blood stem cell transplant helps stop the growth of abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem 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 cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening.

PURPOSE: This phase I/II trial is studying the side effects and best dose of total-body irradiation when given together with cyclophosphamide and antithymocyte globulin in treating patients with severe aplastic anemia undergoing umbilical cord blood transplant.

Condition	Intervention	Phase
Precancerous/Nonmalignant Condition	Biological: anti-thymocyte globulin Biological: filgrastim Drug: cyclophosphamide Drug: cyclosporine Drug: mycophenolate mofetil Procedure: umbilical cord blood transplantation Radiation: total-body irradiation	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Dose Finding Study of Total Body Irradiation for Conditioning Patients With Severe Aplastic Anemia Transplanted With Umbilical Cord Blood

Resource links provided by NLM:

MedlinePlus related topics: Anemia Cancer

Drug Information available for: Cyclophosphamide Cyclosporine Cyclosporin Mycophenolate mofetil hydrochloride Filgrastim Mycophenolate Mofetil

U.S. FDA Resources

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

Primary Outcome Measures:

Toxicity [ Designated as safety issue: Yes ]
Engraftment [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	February 2006
Estimated Primary Completion Date:	February 2011 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the lowest dose of total-body irradiation combined with cyclophosphamide and antithymocyte globulin that will achieve sustained engraftment in patients with severe aplastic anemia undergoing related or unrelated umbilical cord blood transplantation.

OUTLINE: This is a prospective, dose-finding study of total-body irradiation (TBI).

Myeloablative conditioning regimen: Patients receive cyclophosphamide IV on days -7 to -4, -6 to -3, or -5 to -2 and anti-thymocyte globulin IV on days -6 to -4, -5 to -3, or -4 to -2.
TBI: Patients undergo TBI twice daily on days -3, -2, and/or -1. Cohorts of 6 patients receive escalating or de-escalating doses of TBI until the optimal dose is determined. The optimal dose is defined as the dose at which ≤ 2 of 6 or 3 of 12 patients experience dose-limiting toxicity and ≤ 1 of 6 or 1 of 12 patients fail to engraft.
Umbilical cord blood transplantation (UCBT): Patients undergo UCBT on day 0. Patients receive filgrastim (G-CSF) IV or subcutaneously beginning on day 1 and continuing until blood counts recover.
Graft-vs-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV or orally (twice daily for patients ≥ 6 years of age or 3 times daily for patients < 6 years of age) on days -1 to 180 and mycophenolate mofetil IV or orally (twice daily for patients ≥ 50 kg or 3 times daily for patients < 50 kg) beginning 4 hours after UCBT and continuing until approximately day 30.

After completion of study therapy, patients are followed periodically.

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

Eligibility

Ages Eligible for Study:	up to 40 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of life-threatening marrow failure (severe aplastic anemia) of nonmalignant etiology meeting 2 of the following criteria:
- Granulocyte count < 500/mm³
- Corrected reticulocyte count < 1%
- Platelet count < 20,000/mm³
Failed to respond to the best available immunosuppressive treatment protocol by 75 days after initiation of therapy
No paroxysmal nocturnal hemoglobinuria or Fanconi's anemia
No clonal cytogenetic abnormalities or myelodysplastic syndromes
No HLA-identical family member or closely matched (9 or 10 of 10 HLA-locus match) unrelated marrow donor available
Umbilical cord blood (UCB) donor available
- Unrelated UCB donor matched for ≥ 4 of 6 loci or related UCB donor matched for ≥ 3 of 6 loci at the HLA-A and -B antigen level and DRB1 allele level
- If multiple units are selected, the following criteria apply:
  - The UCB units must be matched to each other for ≥ 4 of 6 loci
  - Each unit must contain ≥ 1.5 x 10^7 total nucleated cells (TNC) per kg recipient weight

PATIENT CHARACTERISTICS:

No active fungal infections
HIV negative
No severe disease other than aplastic anemia that would severely limit the probability of survival during the graft procedure
Not pregnant or nursing
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No concurrent aspirin or nonsteroidal anti-inflammatory drugs

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00354419

Locations

United States, Washington
Fred Hutchinson Cancer Research Center	Recruiting
Seattle, Washington, United States, 98104-1024
Contact: Ann E. Woolfrey, MD 206-667-4453
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:

Ann E. Woolfrey, MD

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 ( Ann E. Woolfrey )
Study ID Numbers:	CDR0000486613, FHCRC-2030.00
Study First Received:	July 19, 2006
Last Updated:	July 7, 2009
ClinicalTrials.gov Identifier:	NCT00354419 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

aplastic anemia

Additional relevant MeSH terms:

Anti-Infective Agents
Cyclosporine
Precancerous Conditions
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Mycophenolic Acid
Cyclophosphamide
Antibiotics, Antineoplastic
Cyclosporins
Therapeutic Uses
Antifungal Agents
Mycophenolate mofetil

Anemia, Aplastic
Dermatologic Agents
Alkylating Agents
Hematologic Diseases
Anemia
Enzyme Inhibitors
Immunosuppressive Agents
Pharmacologic Actions
Antilymphocyte Serum
Neoplasms
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Bone Marrow Diseases
Antirheumatic Agents

ClinicalTrials.gov processed this record on November 27, 2009