Fanconi AnemiaPhase 1NCT00272857
Bone Marrow Cell Gene Transfer in Individuals With Fanconi Anemia
A Phase 1 study testing Retrovirus Construct in people with Fanconi Anemia, run by Boston Children's Hospital at 1 site in United States.
Trial summary
Fanconi anemia (FA) is a disease that affects an individual's bone marrow. It is caused by a defective gene in the bone marrow cells that produce various types of blood cells. Individuals with FA may experience fatigue, bleeding, and increased infections. Read more about this study
- Who is it for?
- Ages 1 year to 35 years
- Conditions the study is for
- Fanconi Anemia
- What is being tested?
- Retrovirus Construct
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2004to Oct 2007
- Phase
- Phase 1
- 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 1 year to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- FA, as determined by a positive test for increased sensitivity to chromosomal breakage with mitomycin C or diepoxybutane
- FA complementation group A, as determined by somatic cell hybrids or molecular characterization; transduction of peripheral blood or bone marrow cells with the complementation group of specific retrovirus used in this study must demonstrate correction of mitomycin C sensitivity or cell cycle arrest
- Weighs at least 7.5 kg
- Normal cytogenetics on bone marrow within 3 months of study entry
- A minimum of 2 x 10(6) CD34+ cells/kg after CD34+ selection of the harvested bone marrow or mobilized peripheral blood product must be available to proceed with thaw (if cryopreserved) and transduction
- Human leukocyte antigen (HLA) typing with initial donor limited search results that indicate a potentially acceptable matched unrelated donor in the National Marrow Donor Program database
Who cannot join
- Cancer
- Clonal cytogenetic abnormality on bone marrow or peripheral blood karyotype within 3 months of study entry
- Myelodysplastic syndrome based on the FAB classification including:
- Refractory anemia with ringed sideroblasts (RARS)
- Refractory anemia with excess blasts (RAEB)
- RAEB in transformation (RAEB-T)
Show all 14Show fewer
- Chronic myelomonocytic leukemia (CMML) (myelodysplastic changes in greater than two cell lines, refractory anemia alone, or aplastic anemia with dysplastic changes are permitted)
- Positive baseline screening result for both of the following:
- Detection of Fanconi A proviral sequences by polymerase chain reaction (PCR) analysis
- Detection of replication competent retrovirus by repeat testing by PCR of gibbon ape leukemia virus (GALV) envelope sequence or a positive S+L- assay
- Pregnant or breastfeeding; women of childbearing potential who are enrolled will be advised that the drug may cause birth defects and will be required to use an acceptable form of contraception
- Concurrent enrollment in any other study using an investigational agent, excluding androgens and thyroxine
- Physical or emotional status that would prevent informed consent, protocol compliance, or adequate follow-up with participant or legal guardian
- Participants for whom an acceptable HLA identical matched sibling donor (HLA A, B, DRB1; 6/6 match) has been identified (HLA typing of normal siblings must be documented)
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Official title: Gene Transfer From Patients With Fanconi Anemia, Genotype A: A Pilot Study
Fanconi anemia (FA) is a disease that affects an individual's bone marrow. It is caused by a defective gene in the bone marrow cells that produce various types of blood cells. Individuals with FA may experience fatigue, bleeding, and increased infections. The purpose of this study is to evaluate the safety and effectiveness of a gene transfer procedure in generating new, healthy cells in individuals with FA.
Read the detailed description
FA is a rare, inherited disease that is caused by a gene defect and that primarily affects an individual's bone marrow, resulting in decreased production of blood cells. The lack of white blood cells affects an individual's ability to fight infections, the lack of platelets may result in bleeding, and the lack of red blood cells usually leads to anemia. FA is typically diagnosed in childhood, and there is a high fatality rate. Bone marrow transplants are one common treatment for FA. However, there are many risks associated with transplantation, including rejection of the transplanted cells and graft-versus-host disease, a serious side effect in which donor cells attack the recipient's tissues. This study will use an experimental gene transfer procedure performed in a laboratory to insert a new FA gene into the participant's bone marrow cells. The gene-corrected bone marrow cells will then be re-infused into the participant and participants will be observed for successful gene transfer. The purpose of this study is to evaluate the safety and effectiveness of the FA gene transfer procedure and to determine the ability of the gene-corrected cells at generating new, healthy blood cells in individuals with FA.
This study will enroll individuals with FA. Participants will be required to have the initial bone marrow transfer procedure performed at Cincinnati Children's Hospital, but will be allowed to see their own doctor for the majority of study visits. Participants will first attend a screening visit, which will include a physical exam, blood draw for laboratory testing, and a bone marrow biopsy. Bone marrow cells will be collected from eligible participants and sent to a laboratory for the FA gene transfer procedure. Several days later, the gene-corrected cells will be re-infused back into the participants via an intravenous catheter. Side effects will be closely monitored for 12 hours following the procedure and participants may be required to spend an overnight in the hospital. Following discharge from the hospital, participants will be required to stay in the Cincinnati area for 3 days to undergo daily evaluations and physical examinations. Participants will continue to be followed very closely for the first year after cell re-infusion. Study visits will be held weekly for the first 3 weeks, and then every 3 months for the remainder of the year. Visits will include physical examinations, blood collection, and liver function testing. Bone marrow testing will occur at Months 3, 6, and 12. Follow-up visits will occur yearly for up to 15 years and will include blood collection, a physical exam, and review of medical history.
- Conditions
- Fanconi Anemia
- Being tested
- Retrovirus Construct
- Medical subject headings
- Fanconi Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Retrovirus ConstructGenetic
This study will use an experimental gene transfer procedure performed in a laboratory to insert a new FA gene into the participant's bone marrow cells. The gene-corrected bone marrow cells will then be re-infused into the participant and participants will be observed for successful gene transfer
| Study group | Role | What they receive |
|---|---|---|
| Single arm | Experimental | Not described Receives: Genetic: Retrovirus Construct |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of gene transfer methods
Measured: 3months, 6 months and yearly up to 15 years post gene transfer
Short-term and long-term engraftment of gene-corrected autologous hematopoietic cells (all measured at Year 1)
Measured: 3months, 6 months and yearly up to 15 years post gene transfer
Secondary outcomes (4)
Frequency and function of the integrated recombinant Fanconi vector
Measured: 3months, 6 months and yearly up to 15 years post gene transfer
Efficiency of engraftment of multilineage gene corrected clones
Measured: 3months, 6 months and yearly up to 15 years post gene transfer
Lineage contribution and longevity of molecularly distinguishable gene marked clones
Measured: 3months, 6 months and yearly up to 15 years post gene transfer
Development of myelodysplastic syndrome or overt leukemia (all measured at Year 1)
Measured: 3months, 6 months and yearly up to 15 years post gene transfer
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2006 (estimated)
- Study startAug 2004
- Primary completionOct 2007
- Study completionOct 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fanconi AnemiaStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Children's Hospital Medical Center, Cincinnati
- Responsible party
- Principal investigator, David Williams, Boston Children's Hospital
- Investigators
- Franklin O. Smith, MD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00272857
- Sponsor's protocol ID
- 382
- Other IDs
- R01HL081499, CCHMCEH002, R01HL081499-01A1
- Status last verified
- Jun 2017
- First submitted
- 4 Jan 2006
- Last updated
- 23 Jun 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Kelly PF, Radtke S, von Kalle C, Balcik B, Bohn K, Mueller R, Schuesler T, Haren M, Reeves L, Cancelas JA, Leemhuis T, Harris R, Auerbach AD, Smith FO, Davies SM, Williams DA. Stem cell collection and gene transfer in Fanconi anemia. Mol Ther. 2007 Jan;15(1):211-9. doi: 10.1038/sj.mt.6300033.
PubMed 17164793
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gene Transfer From Patients With Fanconi Anemia, Genotype A: A Pilot Study
- ClinicalTrials.gov ID
- NCT00272857
- Acronym / sponsor ID
- 382
- Conditions
- Fanconi Anemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Children's Hospital Medical Center, Cincinnati
- Study start
- Aug 2004
- Primary completion
- Oct 2007 (actual)
- Study completion
- Oct 2007 (actual)
- First posted
- 9 Jan 2006 (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.
Fanconi anemia (FA) is a disease that affects an individual's bone marrow. It is caused by a defective gene in the bone marrow cells that produce various types of blood cells. Individuals with FA may experience fatigue, bleeding, and increased infections. The purpose of this study is to evaluate the safety and effectiveness of a gene transfer procedure in generating new, healthy cells in individuals with FA.
Detailed description
FA is a rare, inherited disease that is caused by a gene defect and that primarily affects an individual's bone marrow, resulting in decreased production of blood cells. The lack of white blood cells affects an individual's ability to fight infections, the lack of platelets may result in bleeding, and the lack of red blood cells usually leads to anemia. FA is typically diagnosed in childhood, and there is a high fatality rate. Bone marrow transplants are one common treatment for FA. However, there are many risks associated with transplantation, including rejection of the transplanted cells and graft-versus-host disease, a serious side effect in which donor cells attack the recipient's tissues. This study will use an experimental gene transfer procedure performed in a laboratory to insert a new FA gene into the participant's bone marrow cells. The gene-corrected bone marrow cells will then be re-infused into the participant and participants will be observed for successful gene transfer. The purpose of this study is to evaluate the safety and effectiveness of the FA gene transfer procedure and to determine the ability of the gene-corrected cells at generating new, healthy blood cells in individuals with FA.
This study will enroll individuals with FA. Participants will be required to have the initial bone marrow transfer procedure performed at Cincinnati Children's Hospital, but will be allowed to see their own doctor for the majority of study visits. Participants will first attend a screening visit, which will include a physical exam, blood draw for laboratory testing, and a bone marrow biopsy. Bone marrow cells will be collected from eligible participants and sent to a laboratory for the FA gene transfer procedure. Several days later, the gene-corrected cells will be re-infused back into the participants via an intravenous catheter. Side effects will be closely monitored for 12 hours following the procedure and participants may be required to spend an overnight in the hospital. Following discharge from the hospital, participants will be required to stay in the Cincinnati area for 3 days to undergo daily evaluations and physical examinations. Participants will continue to be followed very closely for the first year after cell re-infusion. Study visits will be held weekly for the first 3 weeks, and then every 3 months for the remainder of the year. Visits will include physical examinations, blood collection, and liver function testing. Bone marrow testing will occur at Months 3, 6, and 12. Follow-up visits will occur yearly for up to 15 years and will include blood collection, a physical exam, and review of medical history.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm | Experimental | Genetic: Retrovirus Construct |
Who may qualify
- Ages
- 1 year to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- FA, as determined by a positive test for increased sensitivity to chromosomal breakage with mitomycin C or diepoxybutane
- FA complementation group A, as determined by somatic cell hybrids or molecular characterization; transduction of peripheral blood or bone marrow cells with the complementation group of specific retrovirus used in this study must demonstrate correction of mitomycin C sensitivity or cell cycle arrest
- Weighs at least 7.5 kg
- Normal cytogenetics on bone marrow within 3 months of study entry
- A minimum of 2 x 10(6) CD34+ cells/kg after CD34+ selection of the harvested bone marrow or mobilized peripheral blood product must be available to proceed with thaw (if cryopreserved) and transduction
Key exclusion criteria (14 listed)
- Cancer
- Clonal cytogenetic abnormality on bone marrow or peripheral blood karyotype within 3 months of study entry
- Myelodysplastic syndrome based on the FAB classification including:
- Positive baseline screening result for both of the following:
- Pregnant or breastfeeding; women of childbearing potential who are enrolled will be advised that the drug may cause birth defects and will be required to use an acceptable form of contraception
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 |
|---|---|---|
| Retrovirus ConstructThis study will use an experimental gene transfer procedure performed in a laboratory to insert a new FA gene into the participant's bone marrow cells. The gene-corrected bone marrow cells will then be re-infused into the participant and participants will be observed for successful gene transfer | Genetic | Single arm |
Primary outcome
Safety of gene transfer methods
Time frame: 3months, 6 months and yearly up to 15 years post gene transfer
Short-term and long-term engraftment of gene-corrected autologous hematopoietic cells (all measured at Year 1)
Time frame: 3months, 6 months and yearly up to 15 years post gene transfer
4 secondary outcomes
Frequency and function of the integrated recombinant Fanconi vector
Time frame: 3months, 6 months and yearly up to 15 years post gene transfer
Efficiency of engraftment of multilineage gene corrected clones
Time frame: 3months, 6 months and yearly up to 15 years post gene transfer
Lineage contribution and longevity of molecularly distinguishable gene marked clones
Time frame: 3months, 6 months and yearly up to 15 years post gene transfer
Development of myelodysplastic syndrome or overt leukemia (all measured at Year 1)
Time frame: 3months, 6 months and yearly up to 15 years post gene transfer
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2017.
- Background: PubMed 17164793Kelly PF, Radtke S, von Kalle C, Balcik B, Bohn K, Mueller R, Schuesler T, Haren M, Reeves L, Cancelas JA, Leemhuis T, Harris R, Auerbach AD, Smith FO, Davies SM, Williams DA. Stem cell collection and gene transfer in Fanconi anemia. Mol Ther. 2007 Jan;15(1):211-9. doi: 10.1038/sj.mt.6300033.
- Individual participant dataSharing planned: No
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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.
Franklin O. Smith, MD principal investigator
Children's Hospital Medical Center, Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Retrovirus Construct in people with Fanconi Anemia, run by Boston Children's Hospital 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 6 inclusion and 14 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: finished, as of the sponsor's last update on 23 Jun 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety of gene transfer methods (time frame: 3months, 6 months and yearly up to 15 years post gene transfer). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00272857, which also lists 1 linked publication.
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 23 Jun 2017.