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| Sponsor: | Baylor College of Medicine |
|---|---|
| Information provided by: | Baylor College of Medicine |
| ClinicalTrials.gov Identifier: | NCT00590460 |
Purpose
The purpose of this study is to discover whether children and adults with Fanconi anemia (FA) can be safely and effectively transplanted with HLA mismatched (up to one haplotype), HLA-matched sibling, or unrelated donor stem cells, when leukocytolytic monoclonal antibodies are the sole conditioning agents (patients receiving an HLA mismatched transplant will receive Fludarabine as part of the conditioning regimen). Three monoclonal antibodies will be used in combination. Two of them, YTH 24 and YTH 54 are rat IgG1 antibodies directed against two contiguous epitopes on the CD45 (common leucocyte) antigen. They have been safely administered as part of the conditioning regimen for 12 patients receiving allografts (HLA matched and mismatched) at this center. They produce a transient depletion of >90% circulating leucocytes. The third MAb is Campath 1H, a humanized rat anti-CD52 MAb. This MAb has been widely used to treat B-CLL and more recently has been safely given at this and other centers as part of a sub-ablative conditioning regimen to patients with malignant disease. Because these MAb produce both profound immunosuppression and significant, though transient, myelodestruction we believe they may be useful as the sole conditioning regimen in patients with Fanconi anemia, in whom the use of conventional chemotherapeutic agents for conditioning produces a high rate of short and long term toxicity. We anticipate MAb mediated subablative conditioning will permit engraftment in a high percentage of these patients with little or no immediate or long term toxicity. Campath IH persists in vivo for several days after administration and so will be present over the transplant period to deplete donor T cells as partial GvHD prophylaxis. Additional GvHD prophylaxis will be provided by administration of FK506.
| Condition | Intervention | Phase |
|---|---|---|
|
Fanconi Anemia |
Procedure: CAMPATH-1H Procedure: Anti-CD45 |
Phase II |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Cd45 (Yth-24 and Yth 54) and Cd52 (Campath-1H) Monoclonal Antibody Conditioning Regimen for Allogeneic Donor Stem Cell Transplantation of Patients With Fanconi Anemia |
| Estimated Enrollment: | 27 |
| Study Start Date: | July 2001 |
| Study Completion Date: | March 2010 |
| Primary Completion Date: | March 2010 (Final data collection date for primary outcome measure) |
Show Detailed Description Eligibility| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Diagnosis of Fanconi Anemia or other suspected DNA breakage/chromosomal instability syndromes, such as dyskeratosis congenita or Nijmegen breakage syndrome of all ages are eligible.
Diagnosis of Fanconi anemia confirmed by studies of peripheral blood or bone marrow sensitivity to mitomycin C or DEB or clinical evidence of other DNA breakage/chromosomal instability syndrome as determined by genetic testing or clinical diagnosis by a geneticist
Severe aplasia anemia as evidenced by a hypocellular bone marrow and at least 1 of the 3 criteria below: ANC < 500/mm3 Hemoglobin < 10 gm/dl with reticulocyte count < 1% Platelet count < 50,000/mm3
Availability of an HLA matched or mismatched (up to one haplotype) family member who has been documented not to have Fanconi anemia or of an unrelated HLA matched stem cell donor. Fully matched is defined at 6/6 match by high resolution DR based DNA typing.
Life expectancy greater than 6 weeks limited diseases other than FA
Creatinine 2X normal for age or less
Karnofsky score 70% or more
Exclusion Criteria:
Patients with symptomatic cardiac disease, or evidence of significant cardiac disease by echocardiogram (i.e., shortening fraction less than 25%).
Patients with known allergy to rat serum products.
Patients with a severe infection that on evaluation by the Principal Investigator precludes ablative chemotherapy or successful transplantation. Patients with severe personality disorder or mental illness.
Patients with documented HIV positivity.
Pregnant
NOTE: Patients who would be excluded from the protocol strictly for laboratory abnormalities can be included at the investigator's discretion after approval by the CCGT Protocol Review Committee and the FDA Reviewer.
Contacts and Locations| United States, Texas | |
| Texas Children's Hospital | |
| Houston, Texas, United States, 77030 | |
| Methodist Hospital | |
| Houston, Texas, United States, 77030 | |
| Principal Investigator: | Malcolm Brenner, M.B., Ph.D., | Baylor College of Medicine |
More Information
| Responsible Party: | Malcolm Brenner, Baylor College of Medicine |
| ClinicalTrials.gov Identifier: | NCT00590460 History of Changes |
| Other Study ID Numbers: | H-9938 |
| Study First Received: | December 26, 2007 |
| Last Updated: | April 21, 2010 |
| Health Authority: | United States: Food and Drug Administration |
|
Stem Cell Transplant Fanconi Anemia |
|
Anemia Fanconi Anemia Fanconi Syndrome Hematologic Diseases Anemia, Hypoplastic, Congenital Anemia, Aplastic Bone Marrow Diseases Genetic Diseases, Inborn DNA Repair-Deficiency Disorders Metabolic Diseases Kidney Diseases Urologic Diseases |
Renal Tubular Transport, Inborn Errors Metabolism, Inborn Errors Antibodies Campath 1G Alemtuzumab Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Immunosuppressive Agents |
