Lentiviral-mediated Gene Therapy for Pediatric Patients With Fanconi Anemia Subtype A

Sponsor

Rocket Pharmaceuticals Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04069533

Collaborator

(none)

Enrollment

Location

Arm

37.1

Anticipated Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an open-label Phase II clinical trial to evaluate the efficacy of a hematopoietic cell-based gene therapy for pediatric patients with Fanconi Anemia, subtype A (FA-A).

Hematopoietic stem cells from mobilized peripheral blood of patients with FA-A will be transduced ex vivo (outside the body) with a lentiviral vector carrying the FANCA gene. After transduction, the corrected stem cells will be infused intravenously back to the patient with the goal of preventing bone marrow failure.

Condition or Disease	Intervention/Treatment	Phase
Fanconi Anemia Complementation Group A	Biological: RP-L102	Phase 2

Detailed Description

This is a pediatric open-label Phase II clinical trial to assess the efficacy of a hematopoietic gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the FANCA gene in pediatric subjects with FA-A.

Enriched CD34+ hematopoietic stem cells will be transduced ex vivo with the therapeutic lentiviral vector and infused via intravenous infusion following transduction without any prior conditioning.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

5 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Clinical Trial to Evaluate the Efficacy of the Infusion of Autologous CD34+ Cells Transduced With a Lentiviral Vector Carrying the FANCA Gene (Orphan Drug) in Patients With Fanconi Anemia Subtype A

Actual Study Start Date :

Nov 28, 2019

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Jan 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RP-L102 RP-L102 is CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with lentiviral vector carrying the FANCA gene	Biological: RP-L102 CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with lentiviral vector carrying the FANCA gene

Arm

Intervention/Treatment

Experimental: RP-L102

RP-L102 is CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with lentiviral vector carrying the FANCA gene

Biological: RP-L102

CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with lentiviral vector carrying the FANCA gene

Outcome Measures

Primary Outcome Measures

Phenotypic correction of bone marrow colony forming units after infusion of RP-L102 [3 years]
During months 12-36 post-infusion, the survival of bone marrow colony forming units to 10nM mitomycin C (MMC) increases to over or equal to 10% with respect to values determined at baseline (pretreatment evaluation).

Secondary Outcome Measures

Phenotypic correction of T-lymphocytes in peripheral blood after infusion of RP-L102 [3 years]
Assessment of the percentage of peripheral blood T-cells with diepoxybutane (DEB)-induced chromosomal aberrations that decreases from over or equal to 50% at baseline (defined as the interval between the pre-treatment evaluation and 2 months post-infusion) to less than 50% during the interval between 12 and 36 months post-infusion.
Engraftment of gene-corrected hematopoietic cells after infusion of RP-L102 [3 years]
The level of gene marking of the FANCA-lentiviral vector (LV) provirus in total peripheral blood cells is at least 0.1 vector copy number (VCN) in peripheral blood cells during months 6-36 post-infusion.
Prevention or rescue of bone marrow failure after infusion of RP-L102 [3 years]
Assessment of the need for treatment of bone marrow failure 6-36 months post-infusion. During the 3rd year post-infusion, peripheral blood parameters: hemoglobin levels, neutrophils, and platelets will be assessed and considered stable if they remain at over or equal to 80% of values determined at pre-treatment evaluation visit or immediately prior to mobilization before the administration of granulocyte-colony stimulating factor.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Fanconi anemia as diagnosed by chromosomal fragility assay of cultured lymphocytes in the presence of DEB or a similar DNA-crosslinking agent
Patients of the complementation group FA-A
Minimum age: 1 year and a minimum weight of 8 kg
Maximum age: 17 years
At least 30 CD34+ cells/μL are determined in one bone marrow (BM) aspiration within 3 months prior to CD34+ cell collection OR (see subsequent criterion)
If the number of CD34+ cells/ μL in BM is in the range of 10-29, peripheral blood (PB) parameters should meet two of the three following criteria:

Hemoglobin: ≥11g/dL
Neutrophils: ≥900 cells/μL
Platelets: ≥60,000 cells/μL

Provide informed consent in accordance with current legislation
Women of childbearing age must have a negative urine pregnancy test at the baseline visit, and accept the use of an effective contraception method during participation in the trial

Exclusion Criteria:

Patients with an available and medically eligible human leukocyte antigen (HLA)-identical sibling donor
Evidence of myelodysplastic syndrome or leukemia, or cytogenetic abnormalities other than those predictive of these conditions in BM aspirate analysis. This assessment should be made by valid studies conducted within the 3 months before the patient enters the clinical trial
Patients with somatic mosaicism associated with stable or improved counts in all PB cell lineages
Lansky performance index ≤ 60%
Any concomitant disease or condition that, in the opinion of the Principal Investigator, deems the patient unfit to participate in the trial
Pre-existing sensory or motor impairment > = grade 2 according to the criteria of the National Cancer Institute (NCI)
Pregnant or breastfeeding women
Hepatic dysfunction as defined by either:

Bilirubin > 3 x the upper limit of normal (ULN)
Alanine aminotransferase (ALT ) > 5 x ULN
Aspartate aminotransferase (AST) > 5 x ULN For subjects with bilirubin, ALT, or AST above ULN, a workup to identify the etiology of liver abnormality should be conducted prior to confirmation of eligibility as stipulated in exclusion criterion 5, including evaluation of viral hepatitis, iron overload, drug injury or other causes.

Renal dysfunction requiring either hemodialysis or peritoneal dialysis
Pulmonary dysfunction as defined by either:

Need for supplemental oxygen during the prior 2 weeks (in absence of acute infection)
Oxygen saturation (by pulse oximetry) <90%

Evidence of active metastatic or locoregionally advanced malignancy for which survival is anticipated to be less than 3 years
Subject is receiving androgens (i.e. danazol, oxymetholone)
Subject is receiving other investigational therapy for treatment/prevention of FA-associated bone marrow failure