Combination Chemotherapy in Treating Patients Who Are Undergoing a Donor Stem Cell Transplant for Fanconi's Anemia - Full Text View

Sponsors and Collaborators:	Masonic Cancer Center, University of Minnesota National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00258427

Purpose

RATIONALE: A peripheral stem cell, bone marrow, or umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Giving combination chemotherapy before a donor stem cell transplant may make the transplant more likely to work. This may be an effective treatment for Fanconi's anemia.

PURPOSE: This clinical trial is studying how well combination chemotherapy works in treating patients who are undergoing a donor stem cell transplant for Fanconi's anemia.

Condition	Intervention
Fanconi Anemia Graft Versus Host Disease	Drug: anti-thymocyte globulin Drug: busulfan Drug: cyclophosphamide Drug: cyclosporine Drug: filgrastim Drug: fludarabine phosphate Drug: methylprednisolone Drug: mycophenolate mofetil Procedure: allogeneic bone marrow transplantation Procedure: graft-versus-tumor induction therapy Procedure: peripheral blood stem cell transplantation Procedure: umbilical cord blood transplantation

MedlinePlus related topics: Anemia Bone Marrow Transplantation Cancer

Drug Information available for: Cyclophosphamide Filgrastim Methylprednisolone Fludarabine Fludarabine monophosphate Cyclosporin Cyclosporine Mycophenolate Mofetil Mycophenolate mofetil hydrochloride Busulfan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia MT2002-02

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

Primary Outcome Measures:

Estimate of probability of engraftment at 1 year [ Designated as safety issue: No ]

Estimated Enrollment:	25
Study Start Date:	March 2002

Detailed Description:

OBJECTIVES:

Primary

Determine whether the incidence of neutrophil engraftment is acceptable in high-risk patients with Fanconi's anemia treated with busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin followed by allogeneic hematopoietic stem cell transplantation.

Secondary

Determine the safety and toxicity of this regimen in these patients.
Determine the tolerability of mycophenylate mofetil in these patients.
Determine the incidence of acute and chronic graft-vs-host disease in patients treated with this regimen.
Determine the incidence of major infections in patients with a history of major infections treated with this regimen.
Determine the incidence of relapse in patients with refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or acute myeloid leukemia treated with this regimen
Determine the probability of 1-year survival of patients treated with this regimen.

OUTLINE: Patients are stratified according to donor/recipient HLA type (identical vs other).

Cytoreductive combination chemotherapy: Patients receive busulfan IV over 2 hours twice daily on days -7 and -6 and cyclophosphamide IV over 2 hours and fludarabine IV over 30 minutes once daily on days -5 to -2.
Graft failure prophylaxis: Patients receive methylprednisolone IV twice daily on days -5 to 30 and anti-thymocyte globulin IV over 4-6 hours twice daily on days -5 to -1.
Graft-vs-host disease prophylaxis: Patients receive cyclosporine IV over 2 hours twice daily on days -3 to 100 (if patient has a matched sibling donor) or days -3 to 180 (if patient has another donor type). Patients also receive mycophenylate mofetil orally or IV twice daily on days -3 to 45.
Allogeneic hematopoietic stem cell transplantation (HSCT): Patients undergo allogeneic HSCT (using bone marrow, umbilical cord blood, or peripheral blood) on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 1 and continuing until blood counts recover.

After completion of study treatment, patients are followed periodically for 3 years.

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

Eligibility

Ages Eligible for Study:	up to 44 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of high-risk Fanconi's anemia, as defined by ≥ 1 of the following:
- Advanced myelodysplastic syndromes (MDS)
  - Refractory anemia with excess blasts (RAEB)
  - RAEB in transformation
  - Acute myeloid leukemia
- History of malignancy and currently in remission
- History of systemic fungal or gram-negative bacterial infection
- Severe renal disease with creatinine clearance < 40 mL/min
- Age ≥ 18 years
Has a related or unrelated donor available that meets 1 of the following criteria:
- HLA-A, -B, -DRB1 identical, or 1 antigen mismatched related or unrelated bone marrow or peripheral blood stem cell donor
- HLA-A, -B, -DRB1 identical, or 1 antigen or 2 antigen mismatched related or unrelated umbilical cord blood donor
No aplastic anemia or early MDS at any age with creatinine clearance > 40 mL/min and an HLA-genotypic identical donor
No active CNS leukemia

PATIENT CHARACTERISTICS:

Performance status

Karnofsky 70-100% OR
Lansky 50-100%

Life expectancy

Not specified

Hematopoietic

See Disease Characteristics

Hepatic

No clinical evidence of hepatic failure
No coagulopathy
No cirrhosis
No ascites

Renal

See Disease Characteristics

Cardiovascular

Ejection fraction ≥ 45%

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No active uncontrolled infection

PRIOR CONCURRENT THERAPY: Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00258427

Locations

United States, Minnesota
Masonic Cancer Center at University of Minnesota	Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Clinical Trials Office - Masonic Cancer Center at University o 612-624-2620

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

National Cancer Institute (NCI)

Investigators

Study Chair:

Margaret L. MacMillan, MD

Masonic Cancer Center, University of Minnesota

More Information

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

Study ID Numbers:	CDR0000450841, UMN-2002LS014, UMN-MT2002-02
Study First Received:	November 22, 2005
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00258427
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

graft versus host disease
Fanconi anemia

Study placed in the following topic categories:

Cyclosporine
Clotrimazole
Graft versus host disease
Methylprednisolone
Miconazole
Prednisolone acetate
Cyclophosphamide
Cyclosporins
Fanconi's anemia
Anemia, Aplastic
Mycophenolate mofetil
Methylprednisolone Hemisuccinate
Metabolic Diseases
Hematologic Diseases
Fanconi Anemia

Tioconazole
Anemia
Methylprednisolone acetate
Fludarabine monophosphate
Homologous wasting disease
Antilymphocyte Serum
Genetic Diseases, Inborn
Busulfan
Prednisolone
Graft vs Host Disease
Fludarabine
Metabolic disorder
Aplastic anemia
Bone Marrow Diseases

Additional relevant MeSH terms:

Antimetabolites
Anti-Inflammatory Agents
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
DNA Repair-Deficiency Disorders
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Hormones
Neuroprotective Agents
Therapeutic Uses
Antifungal Agents

Alkylating Agents
Dermatologic Agents
Antineoplastic Agents, Hormonal
Immune System Diseases
Gastrointestinal Agents
Enzyme Inhibitors
Glucocorticoids
Protective Agents
Immunosuppressive Agents
Pharmacologic Actions
Anemia, Hypoplastic, Congenital
Autonomic Agents
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on January 14, 2009