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

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Completed

CT.gov ID

NCT02678533

Collaborator

EuroFancolen (Other)

Enrollment

Location

Arm

26.7

Actual Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Fanconi Anemia	Drug: G-CSF Drug: Plerixafor	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

4 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 10, 2017

Actual Primary Completion Date :

Nov 20, 2018

Actual Study Completion Date :

May 3, 2019

Arms and Interventions

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)

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)

Outcome Measures

Primary Outcome Measures

level of CD34+ cells mobilization [from day 5 to day 8 after the first injection of G-CSF]

Secondary Outcome Measures

number of treatment-related adverse events as a measure of tolerability [30 days after cytapheresis]
Occurrence of adverse effect due to G-CSF and plerixafor administration

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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