Mobilization and Collection of Peripheral Blood Stem Cells in Patients With Fanconi Anemia Using G-CSF and Plerixafor (FancoMob)

December 20, 2021 updated by: Assistance Publique - Hôpitaux de Paris

Pilot Study Assessing the Feasibility of CD34+ Cells Mobilization and Collection After Treatment With G-CSF and Plerixafor in Patients With Fanconi Anemia for Subsequent Treatment by Gene Therapy

The purpose of this study is to assess the feasibility of Plerixafor used in combination with G-CSF (Granulocyte Colony Stimulating Factor) in 5 Fanconi anemia patients to mobilize and collect a sufficient number of peripheral blood CD34+ cells for peripheral blood apheresis, for further gene therapy study.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Fanconi anemia is an autosomal recessive disease with an average survival of around 24 years old. The number of cells producted by bone marrow decreases around 5-10 years old. Hematological symptoms occur around 7 years old. 80% of patients with Fanconi anemia have clinical signs of bone marrow failure in the first decade of life. Generally macrocytosis is the first noticeable sign. Then it leads to thrombocytopenia, anemia and pancytopenia.

Epidemiologic studies show that nearly all of the patients will have medullar aplasia before 40 years old, which is then the first cause of mortality.

It must be emphasized that these complications may occur simultaneously for the same patient, so joint therapeutic intervention is needed.

There is no basic treatment. Some currently used treatments cure cytopenias. These treatments involve blood transfusion, oral androgen, hematopoietic growth factor administration, such as Epo and G-CSF to treat anemia and neutropenia. These treatments are not curative. Hematopoietic stem cell transplantation is the only treatment able to restore permanently hematopoiesis. However, this treatment leads to a high level risk of developing solid tumors and other complications.

All these data justify of developing a stem cells gene therapy treatment using a lentiviral vector expressing wild-type FANCA gene under CIBER promoter.

Three studies have shown the potential number of cells to be mobilized in patients with Fanconi anemia.

The aim is first, to show if administering G-CSF with plerixafor may lead to collect enough cells to potentially perform a gene therapy graft. Secondly the study will assess the tolerance, the stem cells' mobilization kinetic and collected cells' biological features.

This study will be performed in Necker Children Hospital. 8 patients will be enrolled in order to reach 5 treated patients and to analyse how many injections and days are required to reach the cells' number goal.

Sequential blood samples of patients will be drawn to monitor complete blood count (CBC), platelet, CD34+ cells rate and stem cells phenotype.

The clinical and biological data will be anonymously entered in a electronic case report by the investigators up to the end of the study.

Study Type

Interventional

Enrollment (Actual)

4

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75015
        • Hôpital Necker-Enfants Malades

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patient with Fanconi anemia
  • Patient from 2 to 17 years old
  • Potential indication for allogenic bone arrow graft without HLA-identical brotherhood available
  • Patient's weight >10kg
  • Treated and followed for at least the previous two years in a specialized center where they got a full assessment of their disease
  • For women of childbearing age, not pregnant and use of an effective contraception during the entire participation in the research.
  • Affiliated or beneficiary of an health insurance regimen
  • Informed and signed consent

Exclusion Criteria:

  • Patient unable to follow the visits required by the protocol
  • Positive serology for HIV-1/2, HTLV-1/2, HCV and HbS
  • Bacterial, viral, fungal or parasitic active infection with clinical signs
  • Personal history of cancer, myeloproliferative hematopathy or immune deficiency
  • Heart failure and / or heart rhythm disorder
  • History of allogeneic graft of hematopoietic stem cells
  • Patient with an HLA-identical brotherhood donor available
  • Myelodysplasia diagnose on myelogram
  • Cytogenetic abnormality on karyotype
  • Malignant solid tumor
  • Documented spontaneous genetic reversion of medullary process
  • Diagnosis of a psychiatric disorder that could compromise his/her ability to participate in the study
  • Any disorder according to the investigator, that could compromise the ability of patient to give his writing consent and/or to comply with requiring study's procedures
  • Current Pregnancy
  • Heart, kidney or liver failure
  • Current participation in another interventional clinical trial
  • Patient under Medical Assistance State
  • Hypersensitivity to plerixafor or any excipient contained in MOZOBIL®
  • Hypersensitivity to filgrastim or any of its' excipient

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Fanconi anemia
G-CSF and Plerixafor
Drug: G-CSF
D1 to D4 : Injection of 12 µg/kg of G-CSF twice a day . D5 : injection of 12 µg/kg of G-CSF (once/ twice a day according to cytapheresis's realization)
Drug: Plerixafor
D5 : injection of 24mg/kg of plerixafor once a day until cytapheresis has be done (maximum of 4 days)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
level of CD34+ cells mobilization
Time Frame: from day 5 to day 8 after the first injection of G-CSF
from day 5 to day 8 after the first injection of G-CSF

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
number of treatment-related adverse events as a measure of tolerability
Time Frame: 30 days after cytapheresis
Occurrence of adverse effect due to G-CSF and plerixafor administration
30 days after cytapheresis

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

EuroFancolen

Investigators

  • Study Director: Marina CAVAZZANA, MD, PhD, AP-HP, Necker hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 10, 2017

Primary Completion (Actual)

November 20, 2018

Study Completion (Actual)

May 3, 2019

Study Registration Dates

First Submitted

February 5, 2016

First Submitted That Met QC Criteria

February 8, 2016

First Posted (Estimate)

February 9, 2016

Study Record Updates

Last Update Posted (Actual)

December 22, 2021

Last Update Submitted That Met QC Criteria

December 20, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P130103
  • 2014-005264-14 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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