Back to resultsUnrelated HSCT in Patients With Fanconi Anemia
Primary Purpose
Fanconi Anemia
Status
Withdrawn
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
CD34+ selected cells
Sponsored by
About this trial
This is an interventional treatment trial for Fanconi Anemia focused on measuring Fanconi Anemia, compassionate treatment, BMT, HSCT, unrelated, bone marrow transplantation, PBSC, peripheral blood, CD34+
Eligibility Criteria
Inclusion Criteria:
- Patients must be > 2 months and < 21 years of age with a diagnosis of Fanconi anemia.
- Patients must have an HLA-A, B, DRB1 identical or 1 antigen mismatched related (non-sibling) or unrelated donor. Patients and donors will be typed for HLA-A and B using serological or molecular techniques and for DRB1 using high resolution molecular typing. (Patients with a 2 antigen mismatched related donor will be eligible for the protocol but evaluated separately).
- Patients with FA must have high risk genotype or aplastic anemia (AA) or myelodysplastic syndrome without excess blasts.
Aplastic anemia is defined as having at least one of the following:
- platelet count <20 x 109/L
- ANC <5 x 108/L
- Hgb <8 g/dL with at least one of the following:
- transfusion dependence
- supportive care toxicity
- Myelodysplastic syndrome with multilineage dysplasia with or without chromosomal anomalies.
- High risk genotype (e.g. IVS-4 or exon 14 FANCC mutations)
- Adequate major organ function including:
- Cardiac: ejection fraction >45%
- Renal: creatinine clearance >40 mL/min.
- Hepatic: no clinical evidence of hepatic failure (e.g. coagulopathy, ascites)
- Karnofsky performance status >70% or Lansky >50%
- Women of child bearing age must be using adequate birth control and have a negative pregnancy test.
Exclusion Criteria:
- Available HLA-genotypically identical related donor.
- The harvested marrow (prior to TCD) should contain a minimum of 2.5 x 108 nucleated cells/kg recipient body weight with a goal of >5.0 x 108 nucleated cells/kg recipient body weight.
- Positive lymphocytotoxic crossmatch against donor (T cells and B cells)
- History of gram negative sepsis or systemic fungal infection (proven or suspected based on radiographic studies).
- Myelodysplastic syndrome with excess blasts or leukemia.
- Active CNS leukemia at time of HCT.
- Malignant solid tumor (e.g. squamous cell carcinoma of the head/neck/cervix) within 2 years of HCT.
- Pregnant or lactating female.
- Prior radiation therapy preventing use of TBI 450 cGy.
Sites / Locations
- Children's Hospital Los Angeles
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
CD34+ selected cells
Arm Description
use of unrelated bone marrow or peripheral blood for hematopoietic stem cell transplantation with CD34+ selected cells
Outcomes
Primary Outcome Measures
Event free survival post stem cell transplant
Patients who are alive at 5 years post transplants with assessments at 30, 60, 90, 180 and yearly up to 5 years
Secondary Outcome Measures
Peripheral blood CBC counts for engraftment evaluation
Normalization of Hemoglobin, platelets and neutrophil count
Chimerism assay for engraftment evaluation
Assessment of chimerism by FISH or STR on peripheral blood and bone marrow
Graft Versus Host Disease (GVHD) surveillance after HSCT
GHVD disease surveilance done by clinical evaluation, to include history, physical examination, specifically for rash, jaundice, liver dysfunction, nausea and vomiting, diarrhea and failure to thrive
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02127905
Brief Title
Unrelated HSCT in Patients With Fanconi Anemia
Official Title
A Study of Total Body Irradiation, Cyclophosphamide and Fludarabine Followed by Alternated Donor Hematopoietic Cell Transplantation in Patients With Fanconi Anemia
Study Type
Interventional
2. Study Status
Record Verification Date
July 2017
Overall Recruitment Status
Withdrawn
Why Stopped
Study was stopped due to non-enrollment of subjects due to rarity of disease.
Study Start Date
March 2011 (Anticipated)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
March 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Neena Kapoor, M.D.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The protocol is designed for the compassionate treatment of patients with Fanconi Anemia who do not have an HLA-matched sibling donor. The purpose of this study is to determine the likelihood of engraftment in Fanconi Anemia patients using total body irradiation (TBI), cyclophosphamide (CY), fludarabine (FLU) and antithymocyte globulin (ATG) followed by an unrelated donor hematopoietic cell transplant with T-cell depletion using the CliniMACS device.
Detailed Description
The major obstacle to successful alternate donor HCT for patients with Fanconi Anemia is graft failure. While T-cell depletion decreases the incidence of aGVHD, its effect on improving long term survival is unproven. To potentially improve engraftment rate, we have chosen a relatively new immunosuppressive agent, fludarabine (FLU), FLU is an antineoplastic agent that has been shown to be an effective immunosuppressive agen in BMT conditioning therapy. The addition of FLU to the commonly used preparative regimen of CY and TBU in Fanconi Anemia patients may improve engraftment rates.
Based on all presented data and its outcome, hematopoietic stem cell transplantation with the use of total body irradiation (450 cGy), cyclophosphamide (10 mg/kg IV) and fludarabine (35 mg/m2 IV) as preparative cytoreductive therapy has become the standard treatment for the hematologic manifestations of Fanconi Anemia at CHLA. However, the use of Isolex 300i will be replaced by CliniMACS in processing T-cell depletion.
The CliniMACS CD34 Reagent System is an investigational medical device that has not yet been approved by the FDA. This device is used in vitro to select and enrich specific cell populations. When using the CliniMACS CD34 Reagent, the system selects CD34+ cells from heterogenous hematological cell populations for transplantation in cases where this is clinically indicated. Based on the gathered data, CliniMACS has not been a contributing factor in the toxicity of patients, although may have a potential of eliciting "antibody" reactions in some patients, the process has been of significant life-saving benefit as compared to the potential risks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fanconi Anemia
Keywords
Fanconi Anemia, compassionate treatment, BMT, HSCT, unrelated, bone marrow transplantation, PBSC, peripheral blood, CD34+
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CD34+ selected cells
Arm Type
Other
Arm Description
use of unrelated bone marrow or peripheral blood for hematopoietic stem cell transplantation with CD34+ selected cells
Intervention Type
Biological
Intervention Name(s)
CD34+ selected cells
Other Intervention Name(s)
CD34+ selected cells using CliniMACS
Intervention Description
Compassionate treatment of Fanconi Anemia patients with unrelated bone marrow or peripheral blood HSCT followed by the infusion of CD34+ selected cells using CliniMACS
Primary Outcome Measure Information:
Title
Event free survival post stem cell transplant
Description
Patients who are alive at 5 years post transplants with assessments at 30, 60, 90, 180 and yearly up to 5 years
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Peripheral blood CBC counts for engraftment evaluation
Description
Normalization of Hemoglobin, platelets and neutrophil count
Time Frame
3 years
Title
Chimerism assay for engraftment evaluation
Description
Assessment of chimerism by FISH or STR on peripheral blood and bone marrow
Time Frame
3 years
Title
Graft Versus Host Disease (GVHD) surveillance after HSCT
Description
GHVD disease surveilance done by clinical evaluation, to include history, physical examination, specifically for rash, jaundice, liver dysfunction, nausea and vomiting, diarrhea and failure to thrive
Time Frame
3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
8 Weeks
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must be > 2 months and < 21 years of age with a diagnosis of Fanconi anemia.
Patients must have an HLA-A, B, DRB1 identical or 1 antigen mismatched related (non-sibling) or unrelated donor. Patients and donors will be typed for HLA-A and B using serological or molecular techniques and for DRB1 using high resolution molecular typing. (Patients with a 2 antigen mismatched related donor will be eligible for the protocol but evaluated separately).
Patients with FA must have high risk genotype or aplastic anemia (AA) or myelodysplastic syndrome without excess blasts.
Aplastic anemia is defined as having at least one of the following:
platelet count <20 x 109/L
ANC <5 x 108/L
Hgb <8 g/dL with at least one of the following:
transfusion dependence
supportive care toxicity
Myelodysplastic syndrome with multilineage dysplasia with or without chromosomal anomalies.
High risk genotype (e.g. IVS-4 or exon 14 FANCC mutations)
Adequate major organ function including:
Cardiac: ejection fraction >45%
Renal: creatinine clearance >40 mL/min.
Hepatic: no clinical evidence of hepatic failure (e.g. coagulopathy, ascites)
Karnofsky performance status >70% or Lansky >50%
Women of child bearing age must be using adequate birth control and have a negative pregnancy test.
Exclusion Criteria:
Available HLA-genotypically identical related donor.
The harvested marrow (prior to TCD) should contain a minimum of 2.5 x 108 nucleated cells/kg recipient body weight with a goal of >5.0 x 108 nucleated cells/kg recipient body weight.
Positive lymphocytotoxic crossmatch against donor (T cells and B cells)
History of gram negative sepsis or systemic fungal infection (proven or suspected based on radiographic studies).
Myelodysplastic syndrome with excess blasts or leukemia.
Active CNS leukemia at time of HCT.
Malignant solid tumor (e.g. squamous cell carcinoma of the head/neck/cervix) within 2 years of HCT.
Pregnant or lactating female.
Prior radiation therapy preventing use of TBI 450 cGy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Neena Kapoor, M.D.
Organizational Affiliation
Children's Hospital Los Angeles, University of Southern California
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Procedure as well as de-identified data is reported to CIBMTR and is available to other researchers.
IPD Sharing Time Frame
End of subject enrollment and following 2 year subject follow-up
IPD Sharing Access Criteria
Researchers/Investigators interested in severe combined immune deficiency disease treatment and outcomes.
Learn more about this trial
Unrelated HSCT in Patients With Fanconi Anemia
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