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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 : Recruiting
First Posted : May 17, 2017
Last Update Posted : May 17, 2017
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

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.


Condition or disease Intervention/treatment Phase
Fanconi Anemia 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 Phase 1 Phase 2

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: 2 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 : Interventional  (Clinical Trial)
Estimated Enrollment : 5 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Study Start Date : January 2016
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : February 2019


Arm Intervention/treatment
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.
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



Primary Outcome Measures :
  1. 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

  2. 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.


Secondary Outcome Measures :
  1. 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).



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Ages Eligible for Study:   1 Year to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients diagnosed with Fanconi Anemia complementation group A (FA-A)
  • At least one of the following parameters should be lower than the indicated values: Hemoglobin: 8.0 g / dL; Number of neutrophils: 1,000 / mm^3; Number of platelets: 50,000 / mm^3
  • 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.

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): NCT03157804


Contacts
Contact: Julian Sevilla +34 915035938 julian.sevilla@salud.madrid.org

Locations
Spain
Hospital Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Contact: Cristina Diaz de Heredia         
Hospital Infantil del Niño Jesus Recruiting
Madrid, Spain, 28009
Contact: Julian Sevilla    915035938    julian.sevilla@salud.madrid.org   
Sponsors and Collaborators
Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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
Study Director: Juan A Bueren CIEMAT/CIBERER/IIS.FJD

Publications:
Responsible Party: Julian Sevilla, M.D.PhD Specialist in Hematology Hemotherapy, Responsible for the Transfusion Service and Unit for the Obtention and Processing of Hematopoietic Progenitors and other cellular therapies at the Hospital Infantil Universitario Niño Jesús de Madrid., Hospital Infantil Universitario Niño Jesús, Madrid, Spain
ClinicalTrials.gov Identifier: NCT03157804     History of Changes
Other Study ID Numbers: 2011-006100-12
First Posted: May 17, 2017    Key Record Dates
Last Update Posted: May 17, 2017
Last Verified: May 2017

Additional relevant MeSH terms:
Fanconi Anemia
Fanconi Syndrome
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
Lenograstim
JM 3100
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents