Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using a Chemotherapy Only Cytoreduction With Busulfan, Cyclophosphamide and Fludarabine
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|ClinicalTrials.gov Identifier: NCT00987480|
Recruitment Status : Completed
First Posted : October 1, 2009
Results First Posted : July 10, 2018
Last Update Posted : July 10, 2018
This is a genetic disease (transmitted through the parents' genes) called Fanconi Anemia. Because of that genetic disease, the bone marrow has changed and now has failed, or has given rise to a preleukemia called myelodysplastic syndrome (MDS) or leukemia (acute myelogenous leukemia or AML).
Without treatment these complications of Fanconia anemia (FA) are fatal. The only treatment that can cure these complications is an allogeneic transplant of stem cells, meaning, giving the patient bone marrow cells from a healthy donor that can produce normal blood cells that will replace the bone marrow that is sick.
What has been given for the treatment of FA in the past is to use a combination of low doses of radiation to the whole body (total body irradiation) and low doses of the chemotherapy drugs (cyclophosphamide and fludarabine) before the transplant. However, the use of radiation can, later on, increase the chances of getting a second cancer of the skin, head or the neck. These chances of a second cancer are higher than normal in patients with FA.
The purpose of this study is to find out if the doctors can do the same thing with the same chemotherapy drugs used in the past. However physicians will use another chemotherapy drug called busulfan instead of the radiation. The goal of this study is to get rid of the short term and long term risks of the radiation. The first new part of this treatment will be to replace drugs for radiation with chemotherapy drugs.
|Condition or disease||Intervention/treatment||Phase|
|Aplastic Anemia Leukemia Myelodysplastic Syndrome||Drug: Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine. Device: CliniMACS device||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||45 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multicenter Phase II Trial of Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using a Chemotherapy Only Cytoreduction With Busulfan, Cyclophosphamide and Fludarabine|
|Actual Study Start Date :||September 25, 2009|
|Actual Primary Completion Date :||July 10, 2017|
|Actual Study Completion Date :||July 10, 2017|
Experimental: chemotherapy-based cytoreductive regimen plus a CD34+ selected
This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease.
Drug: Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.
There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year.
Device: CliniMACS device
CD34+ T-cell depleted peripheral blood stem cell transplant
- Successful Neutrophil Engraftment [ Time Frame: 2 years ]
- The Incidence of Early Transplant Related Mortality [ Time Frame: 2 years ]
- The Incidence of Acute GvHD [ Time Frame: 100 days ]
- The Incidence of Chronic GvHD [ Time Frame: 2 years ]
- Overall Survival at 3 Years [ Time Frame: 3 years ]Overall Survival is defined as time from date of transplant to event (death from any cause) or last follow-up.
- Disease-free Survival at 3 Years [ Time Frame: 3 years ]
Defined as time from date of transplant to relapse, graft rejection or graft failure, or death.
Primary non-engraftment is diagnosed when the participants fails to achieve an ANC >/= 500/ul at any time in the first 28 days post-transplant.
For participants with MDS or AML, relapse will be analyzed as to type and genetic origin of the MDS/leukemic cells. These will be defined by an increasing number of blasts in the marrow over 5% by the presence of circulating peripheral blasts, or by the presence of blasts in any extramedullary site. Cytogenetic analysis of the marrow and/or peripheral blood will also be obtained for the diagnosis of relapse.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00987480
|United States, Massachusetts|
|Children's Hospital Boston|
|Boston, Massachusetts, United States, 02115|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|The Rockefeller University|
|New York, New York, United States, 10065|
|United States, Ohio|
|Cincinnati Children's Hospital|
|Cincinnati, Ohio, United States, 45229|
|United States, Washington|
|Fred Hutchinson Cancer Research Center|
|Seattle, Washington, United States, 98109|
|United States, Wisconsin|
|Children's Hospital of Wisconsin|
|Milwaukee, Wisconsin, United States|
|Principal Investigator:||Faird Boulad, MD||Memorial Sloan Kettering Cancer Center|