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Lentiviral-mediated Gene Therapy of Fanconi Anemia Patients Subtype A (FANCOLEN-1)

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ClinicalTrials.gov Identifier: NCT03157804
Recruitment Status : Active, not recruiting
First Posted : May 17, 2017
Last Update Posted : November 25, 2020
Sponsor:
Collaborators:
Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT)
Centro de Investigación en Red de Enfermedades Raras (CIBERER)
Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz
Hospital Vall d'Hebron
Universitat Autonoma de Barcelona
Information provided by (Responsible Party):
Julian Sevilla, Hospital Infantil Universitario Niño Jesús, Madrid, Spain

Tracking Information
First Submitted Date  ICMJE April 26, 2017
First Posted Date  ICMJE May 17, 2017
Last Update Posted Date November 25, 2020
Actual Study Start Date  ICMJE January 7, 2016
Actual Primary Completion Date April 23, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 27, 2019)
  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Up to 3 years after infusion of transduced cells ]
    All adverse events will be registered for 3 years from infusion of transduced cells
  • Proportion of patients with at least 0.1 copy of the therapeutic vector per nucleated bone marrow or peripheral blood cells three years after infusion. [ Time Frame: 3 years after infusion of transduced cells ]
    Detection of at least 0.1 copy of the therapeutic vector per nucleated bone marrow cell or peripheral blood cells three years after infusion.
Original Primary Outcome Measures  ICMJE
 (submitted: May 16, 2017)
  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Up to 2 years after infusion of transduced cells ]
    All adverse events will be registered for 2 years from infusion of transduced cells
  • Proportion of patients with at least 0.1 copy of the therapeutic vector per nucleated bone marrow or peripheral blood cells two years after infusion. [ Time Frame: 2 years after infusion of transduced cells ]
    Detection of at least 0.1 copy of the therapeutic vector per nucleated bone marrow cell or peripheral blood cells two years after infusion.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 27, 2019)
Proportion of patients with clinical hematological response after the infusion of autologous CD34 + cells transduced with the therapeutic lentiviral vector [ Time Frame: 3 years after infusion of transduced cells ]
Proportion of patients with clinical hematological response (improvement of cell blood counts at least in one hematological lineage).
Original Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2017)
Proportion of patients with clinical hematological response after the infusion of autologous CD34 + cells transduced with the therapeutic lentiviral vector [ Time Frame: 2 years after infusion of transduced cells ]
Proportion of patients with clinical hematological response (improvement of cell blood counts at least in one hematological lineage).
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 of Fanconi Anemia Patients Subtype A
Official Title  ICMJE Clinical Trial Phase I / II to Evaluate the Safety and Efficacy of the Infusion of Autologous CD34 + Cells Transduced With a Lentiviral Vector Carrying the Gene FANCA in Patients With FA Subtype A (FANCOLEN-1)
Brief Summary

This is an open, Phase I / II clinical trial to evaluate the safety and efficacy of a hematopoietic gene therapy procedure with an orphan drug consisting of a lentiviral vector carrying the FANCA gene for patients with Fanconi Anemia of Subtype A .

CD34 + cells derived from bone marrow and / or mobilized peripheral blood (fresh and / or cryopreserved) from patients with Fanconi subtype A (FA-A), will be transduced ex vivo with a lentiviral vector carrying the gene FANCA (orphan drug) . After transduction the cells will be inoculated in patients in order to restore their hematopoiesis with genetically corrected stem cells.

Detailed Description

The main objective of this open-label Phase I / II clinical trial is to evaluate the safety and therapeutic efficacy of a hematopoietic gene therapy procedure with an orphan drug consisting of a lentiviral vector carrying the FANCA gene for patients with Fanconi's Anemia Subtype A.

The drug to be administered to the patients consists of the cellular product resulting from the transduction of autologous CD34 + cells with the therapeutic lentiviral vector PGK-FANCA.Wpre *.

The dose of cells to infuse in the patients will be that obtained from the transduction process of between 3x10^5 and 4x10^6 CD34 + cells / kg of patient body weight.

The cells will be infused intravenously in a single dose, after complete the transduction process.

Follow-up period: 3 years after infusion of transduced cells. However, patients will be monitored outside the clinical trial over a 10-year period.

Follow-up of the grafted transduced cells will be performed on peripheral blood and bone marrow samples.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Fanconi Anemia
Intervention  ICMJE
  • Procedure: IV administration of Genetically Engineered Hematopoietic Stem/Progenitors Cells (HSPCs)
  • Biological: Genetically Engineered Hematopoietic Stem/Progenitor Cells
    Undergo infusion of genetically modified hematopoietic progenitor cell therapy
    Other Name: Genetically Engineered HSPCs
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Biological: Filgrastim
    Given subcutaneously (SC)
    Other Name: Filgrastim XM02, Filgrastim-sndz, G-CSF (Colony Stimulating Factor), Neupogen, r-metHug-CSF, Recombinant Methionyl Human Granulocyte CSF, rG-CSF, Tbo-filgrastim, Zarxio
  • Drug: Plerixafor
    Given SC
    Other Name: AMD 3100, JM-3100, Mozobil, SDZ SID 791
  • Procedure: Bone Marrow Aspiration
Study Arms  ICMJE Experimental: Autologous CD34+ cells transducted with PGK-FANCA-Wpre *
CD34 + cells from patients with Fanconi subtype A (FA-A) transduced ex vivo with lentiviral vector carrying the gene FANCA, PGK-FANCA-Wpre*The product to be infused consist of a suspension of transduced CD34^+ cells.
Interventions:
  • Procedure: IV administration of Genetically Engineered Hematopoietic Stem/Progenitors Cells (HSPCs)
  • Biological: Genetically Engineered Hematopoietic Stem/Progenitor Cells
  • Other: Laboratory Biomarker Analysis
  • Biological: Filgrastim
  • Drug: Plerixafor
  • Procedure: Bone Marrow Aspiration
Publications *

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 23, 2020)
9
Original Estimated Enrollment  ICMJE
 (submitted: May 16, 2017)
5
Estimated Study Completion Date  ICMJE April 2022
Actual Primary Completion Date April 23, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients diagnosed with Fanconi Anemia complementation group A (FA-A)
  • Minimum age 1 year
  • Maximum age 21 years
  • Lansky Index> 60%.
  • Informed consent in accordance with current legal regulations.
  • Number of cells to be transduced: At least 3x10^5 purified CD34+ / kg body weight.
  • Negative result in the urine pregnancy test at the baseline visit for women of childbearing age, who should be committed to using an effective contraceptive method during the period of study participation.

Exclusion Criteria:

  • Patients with an human leukocyte antigen (HLA) identical family donor.
  • Evidence of myelodysplastic syndrome or leukemia, or cytogenetic abnormalities predicting the same in bone marrow aspirates. In this case, the studies carried out two months in advance of the patient's entry into the clinical trial will be considered valid.
  • Evidence that the patient to be infused has signs of somatic mosaicism, with hematologic improvement.
  • Any illness or concomitant process that in the opinion of the investigator incapacitates the subject for their participation in the study.
  • Pre-existing sensory or motor impairment> = grade 2 according to the National Cancer Institute (NCl) criteria.
  • Pregnant or lactating women.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03157804
Other Study ID Numbers  ICMJE 2011-006100-12
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Julian Sevilla, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
Study Sponsor  ICMJE Hospital Infantil Universitario Niño Jesús, Madrid, Spain
Collaborators  ICMJE
  • Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT)
  • Centro de Investigación en Red de Enfermedades Raras (CIBERER)
  • Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz
  • Hospital Vall d'Hebron
  • Universitat Autonoma de Barcelona
Investigators  ICMJE
Study Director: Juan A Bueren CIEMAT/CIBERER/IIS.FJD
PRS Account Hospital Infantil Universitario Niño Jesús, Madrid, Spain
Verification Date November 2020

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