Fanconi Anemia Complementation Group APhase 2NCT04069533
Lentiviral-mediated Gene Therapy for Pediatric Patients With Fanconi Anemia Subtype A
A Phase 2 study testing RP-L102 in people with Fanconi Anemia Complementation Group A, run by Rocket Pharmaceuticals Inc. at 2 sites in 2 countries.
Trial summary
This is an open-label Phase II clinical trial to evaluate the efficacy of a hematopoietic cell-based gene therapy for pediatric patients with Fanconi Anemia, subtype A (FA-A). Hematopoietic stem cells from mobilized peripheral blood of patients with FA-A will be transduced ex vivo (outside the body) with a lentiviral… Read more about this study
- Who is it for?
- Ages 1 year to 17 years
- Conditions the study is for
- Fanconi Anemia Complementation Group A
- What is being tested?
- RP-L102
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 28 Nov 2019to Feb 2025
- Phase
- Phase 2
- 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 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Fanconi anemia as diagnosed by chromosomal fragility assay of cultured lymphocytes in the presence of diepoxybutane (DEB) or similar DNA-crosslinking agent
- Patient of the complementation group FA-A
- Minimum age: 1 year and minimum weight of 8 kg.
- Maximum age: 17 years
- At least 30 CD34+ cells/µL are determined in one BM aspiration within 3 months prior to the CD34+ cell collection.
- Provide informed consent in accordance with current legislation
- Women of childbearing age must have a negative urine pregnancy test at the baseline visit, and accept the use of an effective contraception method during participation in the trial
Who cannot join
- Patients with an available and medically eligible human leukocyte antigen (HLA)-identical sibling donor
- Evidence of myelodysplastic syndrome or leukemia, or cytogenetic abnormalities other than those predictive of these conditions in bone marrow (BM) aspirate analysis. This assessment should be made by valid studies conducted within the 3 months before the patient enters the clinical trial
- Patients with somatic mosaicism associated with stable or improved counts in all PB cell lineages (If T-lymphocyte chromosomal fragility analysis indicates potential mosaicism, a medically significant decrease in at least one blood lineage over time must be documented to enable eligibility)
- Lansky performance index ≤ 60%
- Any concomitant disease or condition that, in the opinion of the Principal Investigator, deems the patient unfit to participate in the trial
- Pre-existing sensory or motor impairment >/= grade 2 according to the criteria of the National Cancer Institute (NCI)
Show all 18Show fewer
- Pregnant or breastfeeding women
- Hepatic dysfunction as defined by either:
- Bilirubin > 3 x the upper limit of normal (ULN)
- Alanine aminotransferase (ALT ) > 5 x ULN
- Aspartate aminotransferase (AST) > 5 x ULN For subjects with bilirubin, ALT, or AST above ULN, a workup to identify the etiology of liver abnormality should be conducted prior to confirmation of eligibility as stipulated in exclusion criterion 5, including evaluation of viral hepatitis, iron overload, drug injury or other causes.
- Renal dysfunction requiring either hemodialysis or peritoneal dialysis
- Pulmonary dysfunction as defined by either:
- Need for supplemental oxygen during the prior 2 weeks (in absence of acute infection)
- Oxygen saturation (by pulse oximetry) <90%
- Evidence of active metastatic or locoregionally advanced malignancy for which survival is anticipated to be less than 3 years
- Subject is receiving androgens (i.e. danazol, oxymetholone)
- Subject is receiving other investigational therapy for treatment/prevention of FA-associated bone marrow failure
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United Kingdom1 site
University College London Great Ormond Street Institute of Child Health (GOSH)
London, WC1N 1EH
About this study
Official title: A Phase II Clinical Trial to Evaluate the Efficacy of the Infusion of Autologous CD34+ Cells Transduced With a Lentiviral Vector Carrying the FANCA Gene (Orphan Drug) in Patients With Fanconi Anemia Subtype A
This is an open-label Phase II clinical trial to evaluate the efficacy of a hematopoietic cell-based gene therapy for pediatric patients with Fanconi Anemia, subtype A (FA-A).
Hematopoietic stem cells from mobilized peripheral blood of patients with FA-A will be transduced ex vivo (outside the body) with a lentiviral vector carrying the FANCA gene. After transduction, the corrected stem cells will be infused intravenously back to the patient with the goal of preventing bone marrow failure.
Read the detailed description
This is a pediatric open-label Phase II clinical trial to assess the efficacy of a hematopoietic gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the FANCA gene in pediatric subjects with FA-A.
Enriched CD34+ hematopoietic stem cells will be transduced ex vivo with the therapeutic lentiviral vector and infused via intravenous infusion following transduction without any prior conditioning.
- Conditions
- Fanconi Anemia Complementation Group A
- Being tested
- RP-L102
- Keywords
- anemia, bone marrow failure, gene therapy
- Medical subject headings
- Fanconi Syndrome, Anemia, Bone Marrow Failure Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RP-L102Biological
CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with lentiviral vector carrying the FANCA gene
| Study group | Role | What they receive |
|---|---|---|
| RP-L102 | Experimental | RP-L102 is CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with lentiviral vector carrying the FANCA gene Receives: Biological: RP-L102 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phenotypic correction of bone marrow colony forming units after infusion of RP-L102
During months 12-36 post-infusion, the survival of bone marrow colony forming units to 10nM mitomycin C (MMC) increases to over or equal to 10% with respect to values determined at baseline (pretreatment evaluation).
Measured: 3 years
Secondary outcomes (4)
Phenotypic correction of T-lymphocytes in peripheral blood after infusion of RP-L102
Assessment of the percentage of peripheral blood T-cells with diepoxybutane (DEB)-induced chromosomal aberrations that decreases from over or equal to 50% at baseline (defined as the interval between the pre-treatment evaluation and 2 months post-infusion) to less than 50% during the interval between 12 and 36 months post-infusion.
Measured: 3 years
Engraftment of gene-corrected hematopoietic cells after infusion of RP-L102
The level of gene marking of the FANCA-lentiviral vector (LV) provirus in total peripheral blood cells is at least 0.1 vector copy number (VCN) in peripheral blood cells during months 6-36 post-infusion.
Measured: 3 years
Prevention or rescue of bone marrow failure
Assessment of the need for treatment of bone marrow failure.
Measured: 3 years
Short- and long-term Safety
Evaluation of the number of RP-L102 related adverse events
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 posted28 Aug 2019
- Study start28 Nov 2019
- Primary completionFeb 2025 (estimated)
- Study completionFeb 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fanconi Anemia Complementation Group AStudies of the same condition, open and under way.
- More trials run by Rocket Pharmaceuticals Inc.The 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rocket Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Julián Sevilla Navarro, MD, PhD, Principal investigator, Hospital Infantil Universitario Niño Jesús (HIUNJ)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04069533
- Sponsor's protocol ID
- RP-L102-0118
- Other IDs
- 2018-002502-31, 2018
- Status last verified
- May 2024
- First submitted
- 23 Aug 2019
- Last updated
- 22 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Clinical Trial to Evaluate the Efficacy of the Infusion of Autologous CD34+ Cells Transduced With a Lentiviral Vector Carrying the FANCA Gene (Orphan Drug) in Patients With Fanconi Anemia Subtype A
- ClinicalTrials.gov ID
- NCT04069533
- Acronym / sponsor ID
- RP-L102-0118
- Conditions
- Fanconi Anemia Complementation Group A
- Keywords
- anemia, bone marrow failure, gene therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Rocket Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- 28 Nov 2019 (actual)
- Primary completion
- Feb 2025 (estimated)
- Study completion
- Feb 2025 (estimated)
- First posted
- 28 Aug 2019 (actual)
- 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.
This is an open-label Phase II clinical trial to evaluate the efficacy of a hematopoietic cell-based gene therapy for pediatric patients with Fanconi Anemia, subtype A (FA-A).
Hematopoietic stem cells from mobilized peripheral blood of patients with FA-A will be transduced ex vivo (outside the body) with a lentiviral vector carrying the FANCA gene. After transduction, the corrected stem cells will be infused intravenously back to the patient with the goal of preventing bone marrow failure.
Detailed description
This is a pediatric open-label Phase II clinical trial to assess the efficacy of a hematopoietic gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the FANCA gene in pediatric subjects with FA-A.
Enriched CD34+ hematopoietic stem cells will be transduced ex vivo with the therapeutic lentiviral vector and infused via intravenous infusion following transduction without any prior conditioning.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RP-L102 | Experimental | Biological: RP-L102RP-L102 is CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with lentiviral vector carrying the FANCA gene |
Who may qualify
- Ages
- 1 year to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Fanconi anemia as diagnosed by chromosomal fragility assay of cultured lymphocytes in the presence of diepoxybutane (DEB) or similar DNA-crosslinking agent
- Patient of the complementation group FA-A
- Minimum age: 1 year and minimum weight of 8 kg.
- Maximum age: 17 years
- At least 30 CD34+ cells/µL are determined in one BM aspiration within 3 months prior to the CD34+ cell collection.
Key exclusion criteria (18 listed)
- Patients with an available and medically eligible human leukocyte antigen (HLA)-identical sibling donor
- Evidence of myelodysplastic syndrome or leukemia, or cytogenetic abnormalities other than those predictive of these conditions in bone marrow (BM) aspirate analysis. This assessment should be made by valid studies conducted within the 3 months before the patient enters the clinical trial
- Patients with somatic mosaicism associated with stable or improved counts in all PB cell lineages (If T-lymphocyte chromosomal fragility analysis indicates potential mosaicism, a medically significant decrease in at least one blood lineage over time must be documented to enable eligibility)
- Lansky performance index ≤ 60%
- Any concomitant disease or condition that, in the opinion of the Principal Investigator, deems the patient unfit to participate in the trial
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 |
|---|---|---|
| RP-L102CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with lentiviral vector carrying the FANCA gene | Biological | RP-L102 |
Primary outcome
Phenotypic correction of bone marrow colony forming units after infusion of RP-L102
Time frame: 3 years
During months 12-36 post-infusion, the survival of bone marrow colony forming units to 10nM mitomycin C (MMC) increases to over or equal to 10% with respect to values determined at baseline (pretreatment evaluation).
4 secondary outcomes
Phenotypic correction of T-lymphocytes in peripheral blood after infusion of RP-L102
Time frame: 3 years
Engraftment of gene-corrected hematopoietic cells after infusion of RP-L102
Time frame: 3 years
Prevention or rescue of bone marrow failure
Time frame: 3 years
Short- and long-term Safety
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2024.
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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.
Julián Sevilla Navarro, MD, PhD principal investigator
Hospital Infantil Universitario Niño Jesús (HIUNJ)
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RP-L102 in people with Fanconi Anemia Complementation Group A, run by Rocket Pharmaceuticals Inc. at 2 sites in 2 countries.
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 7 inclusion and 18 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: status not confirmed, as of the sponsor's last update on 22 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Spain, United Kingdom. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Phenotypic correction of bone marrow colony forming units after infusion of RP-L102 (time frame: 3 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 22 May 2024.