Lentiviral-mediated Gene Therapy for Pediatric Patients With Fanconi Anemia Subtype A
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04069533|
Recruitment Status : Active, not recruiting
First Posted : August 28, 2019
Last Update Posted : April 6, 2023
- Study Details
- Tabular View
- No Results Posted
- How to Read a Study Record
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.
|Condition or disease||Intervention/treatment||Phase|
|Fanconi Anemia Complementation Group A||Biological: RP-L102||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||7 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||November 28, 2019|
|Estimated Primary Completion Date :||February 2025|
|Estimated Study Completion Date :||February 2025|
RP-L102 is CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with lentiviral vector carrying the FANCA gene
CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with lentiviral vector carrying the FANCA gene
- 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).
- Phenotypic correction of T-lymphocytes in peripheral blood after infusion of RP-L102 [ Time Frame: 3 years ]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.
- Engraftment of gene-corrected hematopoietic cells after infusion of RP-L102 [ Time Frame: 3 years ]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.
- Prevention or rescue of bone marrow failure [ Time Frame: 3 years ]Assessment of the need for treatment of bone marrow failure.
- Short- and long-term Safety [ Time Frame: 3 years ]Evaluation of the number of RP-L102 related adverse events
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||1 Year to 17 Years (Child)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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
- 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)
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04069533
|Hospital Infantil Universitario Niño Jesús (HIUNJ)|
|Madrid, Spain, 28009|
|Principal Investigator:||Julián Sevilla Navarro, MD, PhD||Hospital Infantil Universitario Niño Jesús (HIUNJ)|
|Responsible Party:||Rocket Pharmaceuticals Inc.|
|Other Study ID Numbers:||
2018-002502-31 ( EudraCT Number )
|First Posted:||August 28, 2019 Key Record Dates|
|Last Update Posted:||April 6, 2023|
|Last Verified:||April 2023|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
bone marrow failure
Anemia, Hypoplastic, Congenital
Congenital Bone Marrow Failure Syndromes
Bone Marrow Failure Disorders
Bone Marrow Diseases
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Renal Tubular Transport, Inborn Errors
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Male Urogenital Diseases