Fanconi AnemiaNCT02127905
Unrelated HSCT in Patients With Fanconi Anemia
A study testing CD34+ selected cells in people with Fanconi Anemia, run by Neena Kapoor, M.D. at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 8 weeks to 21 years
- Conditions the study is for
- Fanconi Anemia
- What is being tested?
- CD34+ selected cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2011to Mar 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 weeks to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital Los Angeles
Los Angeles, California, 90027
About this study
Official title: A Study of Total Body Irradiation, Cyclophosphamide and Fludarabine Followed by Alternated Donor Hematopoietic Cell Transplantation in Patients With Fanconi Anemia
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.
Read the 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.
- Conditions
- Fanconi Anemia
- Being tested
- CD34+ selected cells
- Keywords
- Fanconi Anemia, compassionate treatment, BMT, HSCT, unrelated, bone marrow transplantation, PBSC, peripheral blood, CD34+
- Medical subject headings
- Fanconi Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD34+ selected cellsBiological
Also called CD34+ selected cells using CliniMACS
Compassionate treatment of Fanconi Anemia patients with unrelated bone marrow or peripheral blood HSCT followed by the infusion of CD34+ selected cells using CliniMACS
| Study group | Role | What they receive |
|---|---|---|
| CD34+ selected cells | Other | use of unrelated bone marrow or peripheral blood for hematopoietic stem cell transplantation with CD34+ selected cells Receives: Biological: CD34+ selected cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 5 years
Secondary outcomes (3)
Peripheral blood CBC counts for engraftment evaluation
Normalization of Hemoglobin, platelets and neutrophil count
Measured: 3 years
Chimerism assay for engraftment evaluation
Assessment of chimerism by FISH or STR on peripheral blood and bone marrow
Measured: 3 years
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
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2014 (estimated)
- Study startMar 2011 (estimated)
- Primary completionMar 2016
- Study completionMar 2016
Why it stopped: Study was stopped due to non-enrollment of subjects due to rarity of disease.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fanconi AnemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neena Kapoor, M.D.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Neena Kapoor, M.D., Children's Hospital Los Angeles
- Investigators
- Neena Kapoor, M.D., Principal investigator, Children's Hospital Los Angeles, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02127905
- Sponsor's protocol ID
- CCI-10-00176
- Status last verified
- Jul 2017
- First submitted
- 19 Oct 2012
- Last updated
- 11 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Procedure as well as de-identified data is reported to CIBMTR and is available to other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of Total Body Irradiation, Cyclophosphamide and Fludarabine Followed by Alternated Donor Hematopoietic Cell Transplantation in Patients With Fanconi Anemia
- ClinicalTrials.gov ID
- NCT02127905
- Acronym / sponsor ID
- CCI-10-00176
- Conditions
- Fanconi Anemia
- Keywords
- Fanconi Anemia, compassionate treatment, BMT, HSCT, unrelated, bone marrow transplantation, PBSC, peripheral blood
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study was stopped due to non-enrollment of subjects due to rarity of disease.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Neena Kapoor, M.D.University, hospital or other
- Study start
- Mar 2011 (estimated)
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 1 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CD34+ selected cells | Other | Biological: CD34+ selected cellsuse of unrelated bone marrow or peripheral blood for hematopoietic stem cell transplantation with CD34+ selected cells |
Who may qualify
- Ages
- 8 weeks to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (18 listed)
- 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:
- <!-- -->
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CD34+ selected cellsAlso: CD34+ selected cells using CliniMACSCompassionate treatment of Fanconi Anemia patients with unrelated bone marrow or peripheral blood HSCT followed by the infusion of CD34+ selected cells using CliniMACS | Biological | CD34+ selected cells |
Primary outcome
Event free survival post stem cell transplant
Time frame: 5 years
Patients who are alive at 5 years post transplants with assessments at 30, 60, 90, 180 and yearly up to 5 years
3 secondary outcomes
Peripheral blood CBC counts for engraftment evaluation
Time frame: 3 years
Chimerism assay for engraftment evaluation
Time frame: 3 years
Graft Versus Host Disease (GVHD) surveillance after HSCT
Time frame: 3 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2017.
- Individual participant dataSharing planned: Yes. Procedure as well as de-identified data is reported to CIBMTR and is available to other researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Neena Kapoor, M.D. principal investigator
Children's Hospital Los Angeles, University of Southern California
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CD34+ selected cells in people with Fanconi Anemia, run by Neena Kapoor, M.D. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 11 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event free survival post stem cell transplant (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2017.