AzTrials
AzTrials

Fanconi AnemiaPhase 1/2FANCOLEN-1NCT03157804

Lentiviral-mediated Gene Therapy of Fanconi Anemia Patients Subtype A

A Phase 1/2 study testing IV administration of Genetically Engineered Hematopoietic Stem/Progenitors Cells (HSPCs), Genetically Engineered Hematopoietic Stem/Progenitor Cells and Laboratory Biomarker Analysis in people with Fanconi Anemia, run by Hospital Infantil Universitario Niño Jesús, Madrid, Spain at 2 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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 . Read more about this study

Who is it for?
Ages 1 year to 21 years
Conditions the study is for
Fanconi Anemia
What is being tested?
IV administration of Genetically Engineered Hematopoietic Stem/Progenitors Cells (HSPCs), Genetically Engineered Hematopoietic Stem/Progenitor Cells and Laboratory Biomarker Analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
2 sitesSpain
Study dates
7 Jan 2016to 8 Sep 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

2 sites in 1 country.

Spain2 sites

  • Hospital Vall d'Hebron

    Barcelona, 08035

  • Hospital Infantil del Niño Jesus

    Madrid, 28009

Other trials in Spain

About this study

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)

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.

Read the 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.

Conditions
Fanconi Anemia
Being tested
IV administration of Genetically Engineered Hematopoietic Stem/Progenitors Cells (HSPCs), Genetically Engineered Hematopoietic Stem/Progenitor Cells, Laboratory Biomarker Analysis, Filgrastim, Plerixafor
Medical subject headings
Fanconi Anemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IV administration of Genetically Engineered Hematopoietic Stem/Progenitors Cells (HSPCs)Procedure or surgery

  • Genetically Engineered Hematopoietic Stem/Progenitor CellsBiological

    Also called Genetically Engineered HSPCs

    Undergo infusion of genetically modified hematopoietic progenitor cell therapy

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • FilgrastimBiological

    Also called Filgrastim XM02, Filgrastim-sndz, G-CSF (Colony Stimulating Factor), Neupogen, r-metHug-CSF, Recombinant Methionyl Human Granulocyte CSF, rG-CSF, Tbo-filgrastim, Zarxio

    Given subcutaneously (SC)

  • PlerixaforDrug

    Also called AMD 3100, JM-3100, Mozobil, SDZ SID 791

    Given SC

  • Bone Marrow AspirationProcedure or surgery

Study groups in NCT03157804
Study groupRoleWhat they receive
Autologous CD34+ cells transducted with PGK-FANCA-Wpre *ExperimentalCD34 + 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    All adverse events will be registered for 3 years from infusion of transduced cells

    Measured: Up to 3 years after 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.

    Detection of at least 0.1 copy of the therapeutic vector per nucleated bone marrow cell or peripheral blood cells two years after infusion.

    Measured: 2 years after infusion of transduced cells

Secondary outcomes (1)

  1. Proportion of patients with clinical hematological response after the infusion of autologous CD34 + cells transduced with the therapeutic lentiviral vector

    Proportion of patients with clinical hematological response (improvement of cell blood counts at least in one hematological lineage).

    Measured: 2 years after infusion of transduced cells

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 May 2017
  2. Study start7 Jan 2016
  3. Primary completion23 Apr 2019
  4. Study completion8 Sep 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03157804
Sponsor's protocol ID
2011-006100-12
Acronym
FANCOLEN-1
Status last verified
Mar 2024
First submitted
26 Apr 2017
Last updated
21 Mar 2024
Results posted
No

Publications

  • Adair JE, Sevilla J, Heredia CD, Becker PS, Kiem HP, Bueren J. Lessons Learned from Two Decades of Clinical Trial Experience in Gene Therapy for Fanconi Anemia. Curr Gene Ther. 2017;16(5):338-348. doi: 10.2174/1566523217666170119113029.

    PubMed 28103787

  • Molina-Estevez FJ, Nowrouzi A, Lozano ML, Galy A, Charrier S, von Kalle C, Guenechea G, Bueren JA, Schmidt M. Lentiviral-Mediated Gene Therapy in Fanconi Anemia-A Mice Reveals Long-Term Engraftment and Continuous Turnover of Corrected HSCs. Curr Gene Ther. 2015;15(6):550-62. doi: 10.2174/1566523215666150929110903.

    PubMed 26415575

  • Gonzalez-Murillo A, Lozano ML, Alvarez L, Jacome A, Almarza E, Navarro S, Segovia JC, Hanenberg H, Guenechea G, Bueren JA, Rio P. Development of lentiviral vectors with optimized transcriptional activity for the gene therapy of patients with Fanconi anemia. Hum Gene Ther. 2010 May;21(5):623-30. doi: 10.1089/hum.2009.141.

    PubMed 20001454

  • Jacome A, Navarro S, Rio P, Yanez RM, Gonzalez-Murillo A, Lozano ML, Lamana ML, Sevilla J, Olive T, Diaz-Heredia C, Badell I, Estella J, Madero L, Guenechea G, Casado J, Segovia JC, Bueren JA. Lentiviral-mediated genetic correction of hematopoietic and mesenchymal progenitor cells from Fanconi anemia patients. Mol Ther. 2009 Jun;17(6):1083-92. doi: 10.1038/mt.2009.26. Epub 2009 Mar 10.

    PubMed 19277017

  • Rio P, Navarro S, Guenechea G, Sanchez-Dominguez R, Lamana ML, Yanez R, Casado JA, Mehta PA, Pujol MR, Surralles J, Charrier S, Galy A, Segovia JC, Diaz de Heredia C, Sevilla J, Bueren JA. Engraftment and in vivo proliferation advantage of gene-corrected mobilized CD34+ cells from Fanconi anemia patients. Blood. 2017 Sep 28;130(13):1535-1542. doi: 10.1182/blood-2017-03-774174. Epub 2017 Aug 11.

    PubMed 28801449

  • Rio P, Navarro S, Wang W, Sanchez-Dominguez R, Pujol RM, Segovia JC, Bogliolo M, Merino E, Wu N, Salgado R, Lamana ML, Yanez RM, Casado JA, Gimenez Y, Roman-Rodriguez FJ, Alvarez L, Alberquilla O, Raimbault A, Guenechea G, Lozano ML, Cerrato L, Hernando M, Galvez E, Hladun R, Giralt I, Barquinero J, Galy A, Garcia de Andoin N, Lopez R, Catala A, Schwartz JD, Surralles J, Soulier J, Schmidt M, Diaz de Heredia C, Sevilla J, Bueren JA. Successful engraftment of gene-corrected hematopoietic stem cells in non-conditioned patients with Fanconi anemia. Nat Med. 2019 Sep;25(9):1396-1401. doi: 10.1038/s41591-019-0550-z. Epub 2019 Sep 9.

    PubMed 31501599

  • Rio P, Zubicaray J, Navarro S, Galvez E, Sanchez-Dominguez R, Nicoletti E, Sebastian E, Rothe M, Pujol R, Bogliolo M, John-Neek P, Bastone AL, Schambach A, Wang W, Schmidt M, Larcher L, Segovia JC, Yanez RM, Alberquilla O, Diez B, Fernandez-Garcia M, Garcia-Garcia L, Ramirez M, Galy A, Lefrere F, Cavazzana M, Leblanc T, Garcia de Andoin N, Lopez-Almaraz R, Catala A, Barquinero J, Rodriguez-Perales S, Rao G, Surralles J, Soulier J, Diaz-de-Heredia C, Schwartz JD, Sevilla J, Bueren JA; FANCOLEN-1 gene therapy investigators. Haematopoietic gene therapy of non-conditioned patients with Fanconi anaemia-A: results from open-label phase 1/2 (FANCOLEN-1) and long-term clinical trials. Lancet. 2025 Dec 21;404(10471):2584-2592. doi: 10.1016/S0140-6736(24)01880-4. Epub 2024 Dec 3.

    PubMed 39642902

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing IV administration of Genetically Engineered Hematopoietic Stem/Progenitors Cells (HSPCs), Genetically Engineered Hematopoietic Stem/Progenitor Cells and Laboratory Biomarker Analysis in people with Fanconi Anemia, run by Hospital Infantil Universitario Niño Jesús, Madrid, Spain at 2 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03157804, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in