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Lentiviral-mediated Gene Therapy for Pediatric Patients With Fanconi Anemia Subtype A

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ClinicalTrials.gov Identifier: NCT04069533
Recruitment Status : Recruiting
First Posted : August 27, 2019
Last Update Posted : August 27, 2019
Sponsor:
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)
Estimated Enrollment : 5 participants
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
Estimated Study Start Date : August 2019
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : January 2023


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 6-36 post-infusion, the survival of bone marrow colony forming units to 10nM mitomycin C 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 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 6 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-LV provirus in total peripheral blood cells is at least 0.1 vector copy number/peripheral blood cell observed from 0-2 months post-infusion to the 3rd year post-infusion (This should be confirmed in at least 2 determinations conducted at different intervals.).

  3. Prevention or rescue of bone marrow failure after infusion of RP-L102 [ Time Frame: 3 years ]
    Assessment of the need for treatment of bone marrow failure 6-36 months post-infusion. During the 3rd year post-infusion, peripheral blood parameters: hemoglobin levels, neutrophils, and platelets will be assessed and considered stable if they remain at over or equal to 80% of values determined at pre-treatment evaluation visit or immediately prior to mobilization before the administration of granulocyte-colony stimulating factor.



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Ages Eligible for Study:   1 Year to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Fanconi anemia as diagnosed by chromosomal fragility assay of cultured lymphocytes in the presence of DEB or a similar DNA-crosslinking agent
  2. Patients of the complementation group FA-A
  3. Minimum age: 1 year and a minimum weight of 8 kg
  4. Maximum age: 12 years
  5. At least one of the following hematologic parameters below lower limits of normal:

    • Hemoglobin
    • Absolute neutrophils
    • Platelets
  6. At least 30 CD34+ cells/μL are determined in one BM aspiration within 3 months prior to CD34+ cell collection
  7. If the number of CD34+ cells/ μL in BM is in the range of 10-29, PB parameters should meet two of the three following criteria:

    • Hemoglobin: ≥11g/dL
    • Neutrophils: ≥900 cells/μL
    • Platelets: ≥60,000 cells/μL
  8. Provide informed consent in accordance with current legislation
  9. 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 HLA-identical sibling donor
  2. Evidence of myelodysplastic syndrome or leukemia, or cytogenetic abnormalities predictive of these conditions in 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
  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 > 1.5 x the upper limit of normal (ULN)
    • Alanine aminotransferase (ALT ) > 2.5 x ULN
    • Aspartate aminotransferase (ALT) > 2.5 x ULN
  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

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


Contacts
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Contact: Julián Sevilla Navarro, MD, PhD +34 915 035 938 julian.sevilla@salud.madrid.org

Locations
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Spain
Hospital Infantil Universitario Niño Jesús (HIUNJ) Recruiting
Madrid, Spain, 28009
Sponsors and Collaborators
Rocket Pharmaceuticals Inc.
Investigators
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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     History of Changes
Other Study ID Numbers: RP-L102-0118
2018-002502-31 ( EudraCT Number )
First Posted: August 27, 2019    Key Record Dates
Last Update Posted: August 27, 2019
Last Verified: August 2019

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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.:
anemia
bone marrow failure
gene therapy
Additional relevant MeSH terms:
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Fanconi Syndrome
Anemia
Fanconi Anemia
Hematologic Diseases
Anemia, Hypoplastic, Congenital
Anemia, Aplastic
Bone Marrow Diseases
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases
Renal Tubular Transport, Inborn Errors
Kidney Diseases
Urologic Diseases
Metabolism, Inborn Errors