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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 : November 1, 2019
Sponsor:
Information provided by (Responsible Party):
Rocket Pharmaceuticals Inc.

Tracking Information
First Submitted Date  ICMJE August 23, 2019
First Posted Date  ICMJE August 27, 2019
Last Update Posted Date November 1, 2019
Estimated Study Start Date  ICMJE October 2019
Estimated Primary Completion Date January 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 30, 2019)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: August 23, 2019)
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).
Change History Complete list of historical versions of study NCT04069533 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 30, 2019)
  • 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 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 23, 2019)
  • 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.
  • 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.).
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Lentiviral-mediated Gene Therapy for Pediatric Patients With Fanconi Anemia Subtype A
Official Title  ICMJE 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
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.

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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Fanconi Anemia Complementation Group A
Intervention  ICMJE Biological: RP-L102
CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with lentiviral vector carrying the FANCA gene
Study Arms  ICMJE 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
Intervention: Biological: RP-L102
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 23, 2019)
5
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2023
Estimated Primary Completion Date January 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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: 17 years
  5. At least 30 CD34+ cells/μL are determined in one bone marrow (BM) aspiration within 3 months prior to CD34+ cell collection OR (see subsequent criterion)
  6. If the number of CD34+ cells/ μL in BM is in the range of 10-29, peripheral blood (PB) parameters should meet two of the three following criteria:

    • Hemoglobin: ≥11g/dL
    • Neutrophils: ≥900 cells/μL
    • Platelets: ≥60,000 cells/μL
  7. Provide informed consent in accordance with current legislation
  8. 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 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 > 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Julián Sevilla Navarro, MD, PhD +34 915 035 938 julian.sevilla@salud.madrid.org
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04069533
Other Study ID Numbers  ICMJE RP-L102-0118
2018-002502-31 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Rocket Pharmaceuticals Inc.
Study Sponsor  ICMJE Rocket Pharmaceuticals Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Julián Sevilla Navarro, MD, PhD Hospital Infantil Universitario Niño Jesús (HIUNJ)
PRS Account Rocket Pharmaceuticals Inc.
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP