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
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
1 other identifier
interventional
45
1 country
6
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Sep 2009
Longer than P75 for phase_2
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 25, 2009
CompletedFirst Submitted
Initial submission to the registry
September 30, 2009
CompletedFirst Posted
Study publicly available on registry
October 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 10, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
July 10, 2017
CompletedResults Posted
Study results publicly available
July 10, 2018
CompletedJuly 10, 2018
June 1, 2018
7.8 years
September 30, 2009
March 2, 2018
June 14, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Successful Neutrophil Engraftment
2 years
The Incidence of Early Transplant Related Mortality
2 years
The Incidence of Acute GvHD
100 days
The Incidence of Chronic GvHD
2 years
Secondary Outcomes (2)
Overall Survival at 3 Years
3 years
Disease-free Survival at 3 Years
3 years
Study Arms (1)
chemotherapy-based cytoreductive regimen plus a CD34+ selected
EXPERIMENTALThis 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.
Interventions
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.
CD34+ T-cell depleted peripheral blood stem cell transplant
Eligibility Criteria
You may qualify if:
- Patients must have a diagnosis of Fanconi anemia (confirmed by mitomycin C or diepoxybutane \[DEB\] chromosomal breakage testing at an approved laboratory).
- Hematologic Diagnosis and Status - Patients must have one of the following hematologic diagnoses:
- Severe Aplastic Anemia (SAA) with bone marrow cellularity of \<25%, or Severe Isolated Single lineage Cytopenia
- AND at least one of the following features:
- Platelet count \<20 x 109/L or platelet transfusion dependence\*
- ANC \<1000 x 109/L
- Hgb \<8 gm/dl or red cell transfusion dependence\*
- Myelodysplastic Syndrome (MDS) (Appendix 1: MDS Classification) - MDS at any stage, based on either one of the following classifications:
- WHO Classification
- Refractory anemia and transfusion dependence\*
- Any of other stages
- IPSS Classification
- Low risk (score 0) and transfusion dependence\*
- Any other risk groups Score \> or = to 0.5
- Acute Myelogenous Leukemia
- +22 more criteria
You may not qualify if:
- Active CNS leukemic involvement
- Female patients who are pregnant (positive serum or urine HCG) or breast-feeding. Women of childbearing age must avoid becoming pregnant while on study.
- Active uncontrolled viral, bacterial or fungal infection
- Patient seropositive for HIV-I/II; HTLV -I/II
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Memorial Sloan Kettering Cancer Centerlead
- Boston Children's Hospitalcollaborator
- Children's Hospital Medical Center, Cincinnaticollaborator
- Children's Hospital and Health System Foundation, Wisconsincollaborator
- Rockefeller Universitycollaborator
- Fred Hutchinson Cancer Centercollaborator
Study Sites (6)
Children's Hospital Boston
Boston, Massachusetts, 02115, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
The Rockefeller University
New York, New York, 10065, United States
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States
Related Publications (2)
van Hoogdalem MW, Emoto C, Fukuda T, Mizuno T, Mehta PA, Vinks AA. Population pharmacokinetic modelling of busulfan and the influence of body composition in paediatric Fanconi anaemia patients. Br J Clin Pharmacol. 2020 May;86(5):933-943. doi: 10.1111/bcp.14202. Epub 2020 Jan 23.
PMID: 31851762DERIVEDMehta PA, Davies SM, Leemhuis T, Myers K, Kernan NA, Prockop SE, Scaradavou A, O'Reilly RJ, Williams DA, Lehmann L, Guinan E, Margolis D, Baker KS, Lane A, Boulad F. Radiation-free, alternative-donor HCT for Fanconi anemia patients: results from a prospective multi-institutional study. Blood. 2017 Apr 20;129(16):2308-2315. doi: 10.1182/blood-2016-09-743112. Epub 2017 Feb 8.
PMID: 28179273DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Farid Boulad
- Organization
- Memorial Sloan Kettering Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Faird Boulad, MD
Memorial Sloan Kettering Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 30, 2009
First Posted
October 1, 2009
Study Start
September 25, 2009
Primary Completion
July 10, 2017
Study Completion
July 10, 2017
Last Updated
July 10, 2018
Results First Posted
July 10, 2018
Record last verified: 2018-06