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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
Information provided by (Responsible Party):
Rocket Pharmaceuticals Inc.

Brief 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 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

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Arm Intervention/treatment
Experimental: RP-L102
RP-L102 is CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with lentiviral vector carrying the FANCA gene
Biological: RP-L102
CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with lentiviral vector carrying the FANCA gene

Primary Outcome Measures :
  1. 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).

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. Prevention or rescue of bone marrow failure [ Time Frame: 3 years ]
    Assessment of the need for treatment of bone marrow failure.

  4. Short- and long-term Safety [ Time Frame: 3 years ]
    Evaluation of the number of RP-L102 related adverse events

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Fanconi anemia as diagnosed by chromosomal fragility assay of cultured lymphocytes in the presence of diepoxybutane (DEB) or similar DNA-crosslinking agent
  2. Patient of the complementation group FA-A
  3. Minimum age: 1 year and minimum weight of 8 kg.
  4. Maximum age: 17 years
  5. At least 30 CD34+ cells/µL are determined in one BM aspiration within 3 months prior to the CD34+ cell collection.
  6. Provide informed consent in accordance with current legislation
  7. 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

Exclusion Criteria:

  1. Patients with an available and medically eligible human leukocyte antigen (HLA)-identical sibling donor
  2. 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
  3. 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)
  4. Lansky performance index ≤ 60%
  5. Any concomitant disease or condition that, in the opinion of the Principal Investigator, deems the patient unfit to participate in the trial
  6. Pre-existing sensory or motor impairment >/= grade 2 according to the criteria of the National Cancer Institute (NCI)
  7. Pregnant or breastfeeding women
  8. 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.
  9. Renal dysfunction requiring either hemodialysis or peritoneal dialysis
  10. 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%
  11. Evidence of active metastatic or locoregionally advanced malignancy for which survival is anticipated to be less than 3 years
  12. Subject is receiving androgens (i.e. danazol, oxymetholone)
  13. Subject is receiving other investigational therapy for treatment/prevention of FA-associated bone marrow failure

Information from the National Library of Medicine

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

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Hospital Infantil Universitario Niño Jesús (HIUNJ)
Madrid, Spain, 28009
Sponsors and Collaborators
Rocket Pharmaceuticals Inc.
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Principal Investigator: Julián Sevilla Navarro, MD, PhD Hospital Infantil Universitario Niño Jesús (HIUNJ)
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Responsible Party: Rocket Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT04069533    
Other Study ID Numbers: RP-L102-0118
2018-002502-31 ( EudraCT Number )
First Posted: August 28, 2019    Key Record Dates
Last Update Posted: April 6, 2023
Last Verified: April 2023

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Rocket Pharmaceuticals Inc.:
bone marrow failure
gene therapy
Additional relevant MeSH terms:
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Fanconi Syndrome
Fanconi Anemia
Hematologic Diseases
Anemia, Hypoplastic, Congenital
Anemia, Aplastic
Congenital Bone Marrow Failure Syndromes
Bone Marrow Failure Disorders
Bone Marrow Diseases
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases
Renal Tubular Transport, Inborn Errors
Kidney Diseases
Urologic Diseases
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Male Urogenital Diseases