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
- Conditions
- Fanconi anemia (subtype A)MedDRA version: 20.0Level: LLTClassification code 10055206Term: Fanconi's anemiaSystem Organ Class: 100000004850Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2018-002502-31-GB
- Lead Sponsor
- Rocket Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 5
1. FA as diagnosed by chromosomal fragility assay of cultured lymphocytes in the presence of DEB or a similar DNA-crosslinking agent
2. Patients of the complementation group FA-A
3. Minimum age: 1 year and a minimum weight of 8 kg.
4. Maximum age: 17 years
5. At least 30 CD34+ cells/µL are determined in one BM aspiration within 3 months prior to CD34+ cell collection OR (see subsequent criterion)
6. If the number of CD34+ cells/µL in BM is in the range of 10–29, PB parameters should meet two of the three following criteria:
• Hemoglobin: =11g/dL
• Neutrophils: =900 cells/µL
• Platelets: =60,000 cells/µL
7. Provide informed consent in accordance with current legislation
8. Women of childbearing age must have a negative urine pregnancy test at the baseline visit, specifically within 14 days prior to infusion of IMP and must accept the use of an effective contraception method during participation in the trial as defined in the note below.
Note: Female patients of childbearing potential (e.g., are menstruating or could reach menarche during the study) should be counselled on the need for contraception should they be sexually active or, in the opinion of the Investigator, likely to be sexually active. Such subjects must agree to the use of contraception as defined in the subsequent paragraph. Male patients who are sexually active must agree to use a condom during intercourse for the duration of their participation in the study.
Acceptable methods of contraception for female subjects of childbearing potential include the following:
- male or female condom with or without spermicide;
- cap, diaphragm or sponge with spermicide;
- intrauterine device (IUD);
- bilateral tubal occlusion;
- vasectomised partner;
- sexual abstinence.
Are the trial subjects under 18? yes
Number of subjects for this age range: 5
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Patients with an available and medically eligible HLA-identical sibling donor
2. Evidence of myelodysplastic syndrome or leukaemia, or cytogenetic abnormalities other than those reported as variant(s) of normal in BM aspirate analysis. This assessment should be made by valid studies conducted within the 3 months before the patient enters the clinical trial
3. Patients with somatic mosaicism associated with stable or improved counts in all PB cell lineages (If T-lymphocyte chromosomal fragility analysis indicates potential mosaicism, a medically significant decrease in at least one blood lineage over time must be documented to enable eligibility)
4. Lansky performance index =60%
5. Any concomitant disease or condition that, in the opinion of the Principal Investigator, deems the patient unfit to participate in the trial
6. Pre-existing sensory or motor impairment =grade 2 according to the criteria of the National Cancer Institute (NCI)
7. Pregnant or breastfeeding women
8. Hepatic dysfunction as defined by either:
• Bilirubin > 3.0× the upper limit of normal (ULN)
• Alanine aminotransferase (ALT) >5.0× ULN
• Aspartate aminotransferase (AST) >5.0× 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.
9. Renal dysfunction requiring either hemodialysis or peritoneal dialysis
10. 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%.
11. Evidence of active metastatic or locoregionally advanced malignancy for which survival is anticipated to be less than 3 years
12. Subject is receiving androgens (i.e., danazol, oxymetholone)
13. Subject is receiving other investigational therapy for treatment/prevention of FA-associated bone marrow failure.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The main objective of this trial is to assess the therapeutic efficacy of a haematopoietic gene therapy procedure with an orphan drug consisting of a LV carrying the FANCA gene in patients with FA-A.;Secondary Objective: Not applicable;Primary end point(s): The primary endpoint of this study is the extent of phenotypic correction to mosaic or normal range as determined by MMC-resistance of bone marrow colony forming cells (also known as colony forming units or CFUs), targeting an increase of at least 10% BM CFUs resistant to 10 nM MMC at any timepoint at least 12 months subsequent to investigational infusion (progressive increases in the percentage of resistant cells over at least 2 points in time will be considered confirmatory).;Timepoint(s) of evaluation of this end point: Up to 3 years after infusion
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Level of phenotypic correction of haematopoietic cells as determined by additional parameters (T-lymphocyte chromosomal fragility assay; targeting fewer than 50% aberrant cells following DEB-culture and a minimum decrease of at least 20% from baseline) after the infusion of the IMP in subjects with FA-A.<br>2. Level of engraftment of gene-corrected haematopoietic cells after the infusion of the IMP in subjects with FA-A.<br>3. Clinical response: prevention or rescue of BMF after the infusion of the IMP in subjects with FA-A.<br>4. Ongoing evaluation of the short- and long-term safety of the infusion of the IMP in subjects with FA-A.;Timepoint(s) of evaluation of this end point: Up to 3 years after infusion