Phase I/II Study of Total Body Irradiation, Cyclophosphamide, and Fludarabine Followed by Alternate Donor Hematopoietic Cell Transplantation in Patients With Fanconi's Anemia - Full Text View

Sponsored by:	University of Minnesota
Information provided by:	Office of Rare Diseases (ORD)
ClinicalTrials.gov Identifier:	NCT00005898

Purpose

OBJECTIVES: I. Determine the probability of engraftment with total body irradiation, cyclophosphamide, fludarabine, and anti-thymocyte globulin followed by HLA nongenotypically identical donor, T-cell depleted hematopoietic cell transplantation in patients with Fanconi's anemia.

II. Determine the incidence of acute and chronic graft-versus-host disease in these patients after undergoing this treatment regimen.

III. Determine the one-year survival rate in these patients after undergoing this treatment regimen.

IV. Determine the toxicity of this treatment regimen in these patients. V. Determine the incidence of relapse in patients with myelodysplastic syndrome or acute myeloid leukemia after undergoing this treatment regimen.

Condition	Intervention	Phase
Fanconi's Anemia	Drug: anti-thymocyte globulin Drug: cyclophosphamide Drug: cyclosporine Drug: filgrastim Drug: fludarabine Drug: methylprednisolone	Phase I Phase II

MedlinePlus related topics: Anemia Radiation Therapy

Drug Information available for: Cyclophosphamide Fludarabine Cyclosporine Fludarabine monophosphate Cyclosporin Methylprednisolone Filgrastim

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment

Further study details as provided by Office of Rare Diseases (ORD):

Estimated Enrollment:	30
Study Start Date:	February 2000

Detailed Description:

PROTOCOL OUTLINE: Donor bone marrow, peripheral blood, or umbilical cord blood is processed to harvest CD34+ cells.

Patients receive preparative cytoreductive therapy comprising total body irradiation on day -6; cyclophosphamide IV over 2 hours on days -5 to

2; fludarabine IV over 30 minutes on days -5 to -2; methylprednisone IV on days -5 to 24; anti-thymocyte globulin IV over 4-6 hours on days -5 to -1; cyclosporine IV over 2 hours every 12 hours (every 8 hours for patients less than 40 kg in weight) on days -3 to 180, and then tapering in the absence of graft-versus-host disease; hematopoietic cell transplantation on day 0; and filgrastim (G-CSF) IV starting on day 1 and continuing until blood counts recover. Patients are followed at days 60, 90, and 180, and then annually for 3 years.

Eligibility

Ages Eligible for Study:	up to 34 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Patients with a diagnosis of Fanconi's anemia AND Aplastic anemia OR Myelodysplastic syndrome OR Acute leukemia with or without chromosomal anomalies Aplastic anemia as defined by having at least one of the following: Platelet count less than 20,000/mm3 Absolute neutrophil count less than 500/mm3 Hemoglobin less than 8 g/dL
Myelodysplastic syndrome with multilineage dysplasia With or without chromosomal anomalies
Hematologic malignancy (e.g., acute myeloid leukemia, acute lymphoblastic leukemia, or B-cell non-Hodgkin's lymphoma)
No greater than 30% blasts in bone marrow or greater than 5% blasts in peripheral blood
No active CNS leukemia at time of transplantation
Must have an HLA A, B, DRB1 identical or 1 antigen mismatched related (nonsibling) or unrelated bone marrow, peripheral blood, or umbilical cord blood donor

--Prior/Concurrent Therapy--

Radiotherapy: No prior radiotherapy that would preclude total body irradiation
Surgery: Not specified

--Patient Characteristics--

Performance status: Karnofsky 70-100% OR Lansky 50-100%
Hematopoietic: See Disease Characteristics
Hepatic: No hepatic failure (e.g., coagulopathy or ascites)
Renal: Creatinine clearance at least 40 mL/min
Cardiovascular: Ejection fraction at least 45%
Other: No active uncontrolled infection within one week of transplantation No malignant solid tumor (e.g., squamous cell carcinoma of the head, neck, or cervix) within 2 years of transplantation Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005898

Locations

United States, Minnesota
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States, 55455

Sponsors and Collaborators

University of Minnesota

Investigators

Study Chair:

John E. Wagner, Jr.

University of Minnesota

More Information

No publications provided

Study ID Numbers:	199/15109, UMN-MT-1999-05, UMN-MT9905
Study First Received:	June 2, 2000
Last Updated:	June 23, 2005
ClinicalTrials.gov Identifier:	NCT00005898 History of Changes
Health Authority:	Unspecified

Study placed in the following topic categories:

Antimetabolites
Anti-Inflammatory Agents
Cyclosporine
Immunologic Factors
Clotrimazole
Aplastic Anemia
Methylprednisolone
Hormone Antagonists
Miconazole
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Prednisolone acetate
Cyclophosphamide
Hormones
Neuroprotective Agents

Cyclosporins
Fanconi's Anemia
Antifungal Agents
Anemia, Aplastic
Alkylating Agents
Metabolic Disorder
Methylprednisolone Hemisuccinate
Metabolic Diseases
Antineoplastic Agents, Hormonal
Hematologic Diseases
Fanconi Anemia
Tioconazole
Anemia
Methylprednisolone acetate
Fludarabine monophosphate

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Anti-Infective Agents
Cyclosporine
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Methylprednisolone
Physiological Effects of Drugs
DNA Repair-Deficiency Disorders
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Cyclosporins
Hormones
Therapeutic Uses
Dermatologic Agents
Methylprednisolone Hemisuccinate

Metabolic Diseases
Antineoplastic Agents, Hormonal
Hematologic Diseases
Glucocorticoids
Fludarabine
Antimetabolites
Immunologic Factors
Antineoplastic Agents
Prednisolone acetate
Cyclophosphamide
Neuroprotective Agents
Antifungal Agents
Anemia, Aplastic
Alkylating Agents
Fanconi Anemia

ClinicalTrials.gov processed this record on May 07, 2009