Clinical Phase II Trial to Evaluate CD34+ Cells Mobilization and Collection in Patients With Fanconi Anemia for Subsequent Transduction With a Lentiviral Vector Carring FANCA Gene. FANCOSTEM-1

Clinical Phase II Trial to Evaluate Efficacy and Safety of CD34+ Cells Mobilization and Collection After Treatment With Plerixafor and Filgrastim in Patients With Fanconi Anemia for Subsequent Transduction With a Lentiviral Vector Carring FANCA Gene and Reinfusion in the Patient

Fanconi anemia (FA) is a congenital disease characterized by bone marrow failure and increased incidence of malignant tumors. The Project pursue the optimization of the collection of hematopoietic progenitor cells for later use in another clinical trial entitled "Clinical Trial Phase I/II to evaluate the safety and efficacy of the infusion of autologous CD34+ cells mobilized with mozobil and filgrastim, and transduced with a lentiviral vector carrying the FANCA gene (Orphan Drug) for patients with Fanconi Anemia Subtype A ". The objectives of this study are, therefore, to assess the safety and efficacy of CD34+ cells mobilization with mozobil and filgrastim, which is postulated the most efficient for the collection of CD34+ cells from FA patients.

Study Overview

• Status: Completed
• Conditions: Fanconi Anemia
• Intervention / Treatment: Drug: filgrastim; Drug: plerixafor

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28009
    • Hospital Infantil Universitario Niño Jesús

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 64 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female > 1 year
• diagnosed of Fanconi's anemia confirmed by instability chromosomal test with diepoxy-butane or mitomycin C
• At least one of the following parameters must be higher than these values: Hemoglobin:8,0 g/dL; neutrophils: 750/mm3; platelets: 30.000/mm3
• Lansky index> 60%.
• Left ventricular ejection fraction >50%.
• To grant informed consent in agreement with current law norms
• Women in childbearing age must obtain a negative result in the pregnancy test in serum or urine in the visit of selection and accept the use of suitable contraceptive methods since at least 14 days prior to the first dose of mobilizing treatment until the 14 days following the last

Exclusion Criteria:

• Evidence of myelodysplastic syndromes or leukemia, or cytogenetic abnormalities predicted of these syndromes in bone marrow aspiration. Cytogenetic analyses performed 2 months before starting study are accepted
• Patients with active infection process or any other underlaying severe medical process
• Severe Functional alteration of organs (hepatic, renal, respiratory)(?3), according to National Cancer Institute (NCI CTCAE v3) criteria
• Haematopoietic transplant
• Any disease or concomitant process that is not compatible with the study as per investigator opinion
• Patients not elegible because of an psico-social evaluation
• Patients that received transfusional support during the last 3 months.
• Pregnant or breastfeeding women

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: plerixafor and filgrastim treatment; to assess the safety and efficacy of CD34+ cells mobilization with plerixafor and filgrastim	Drug: filgrastim; G-CSF (12 μg/Kg/12 h) 8 days.; Drug: plerixafor; Plerixafor 0,24 mg/kg/day after the fourth day of G-CSF, and until 5 cells CD34+/μL, max 4 doses of plerixafor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity of the mobilization procedure according to National Cancer Institute (CTC NCI, versión 3.0)	At a year (± 30 days) after the last apheresis, a complete physical examination, blood cell count, basic biochemistry and bone marrow aspirate will be done to the patient in order to control their general health status.	after 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients that reach >5 CD34+ cells/mcl after treatment with filgrastim and plerixafor	mobilization protocol will be determined by the percentage of patients who achieve peripheral blood counts exceeding 5 CD34+ cells /microliter	after 8 days
Percentage of patients that reach a total CD34+ yield >4x10E6/kg, using the estimated weight of the patient in 5 years	the CD34+ cell collection protocol will be determined by the percentage of patients who reach at least one million CD34 + cells per kilogram of body weight projected to 5 years after the mobilization process	after 8 days
Percentage of samples in which the recovery of CD34+ cells after the immunomagnetic selection procedure is >50%	the of CD34+ cell selection process will be determined by the proportion of immunoselected samples where the recovery of CD34 + cells is at least 50%, and where the final percentage of CD34+ cells is at least 50%	after 8 days
Percentage of patients in which the CD34+ cells after the immunomagnetic selection is ³ 4x10E6/kg, using the projected weight at 5 years	will be determined by the percentage of patients who reach at least one million CD34 + cells per kilo of weight projected to 5 years after the immunomagnetic selection process of all the collected cells	after 8 days

Collaborators and Investigators

• Sponsor: Hospital Universitari Vall d'Hebron Research Institute
• Collaborators: CIEMAT; CIBERER
• Investigators: Principal Investigator: Cristina Díaz de Heredia, MD, PhD, Hospital Vall d'Hebron

Publications and helpful links

General Publications

• Sevilla J, Navarro S, Rio P, Sanchez-Dominguez R, Zubicaray J, Galvez E, Merino E, Sebastian E, Azqueta C, Casado JA, Segovia JC, Alberquilla O, Bogliolo M, Roman-Rodriguez FJ, Gimenez Y, Larcher L, Salgado R, Pujol RM, Hladun R, Castillo A, Soulier J, Querol S, Fernandez J, Schwartz J, Garcia de Andoin N, Lopez R, Catala A, Surralles J, Diaz-de-Heredia C, Bueren JA. Improved collection of hematopoietic stem cells and progenitors from Fanconi anemia patients for gene therapy purposes. Mol Ther Methods Clin Dev. 2021 Jun 12;22:66-75. doi: 10.1016/j.omtm.2021.06.001. eCollection 2021 Sep 10.

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): October 1, 2018
• Study Completion (Actual): October 1, 2018

Study Registration Dates

• First Submitted: September 6, 2016
• First Submitted That Met QC Criteria: October 10, 2016
• First Posted (Estimate): October 12, 2016

Study Record Updates

• Last Update Posted (Actual): May 27, 2020
• Last Update Submitted That Met QC Criteria: May 25, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Bone Marrow Diseases; Hematologic Diseases; Genetic Diseases, Inborn; DNA Repair-Deficiency Disorders; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Renal Tubular Transport, Inborn Errors; Anemia; Fanconi Syndrome; Fanconi Anemia; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Plerixafor
• Other Study ID Numbers: FANCOSTEM-1; 2011-006197-88 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No