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Gene Therapy Trial Report

Summary

ALS20-101 Lentiviral Gene Therapy for Beta Thalassemia


NCTID NCT06364774 (View at clinicaltrials.gov)
Description
Development Status Active
Indication Beta-Thalassemia Major
Disease Ontology Term DOID:0080771
Compound Name CHOP-ALS20
Compound Description βA-T87Q-globin
Sponsor Children's Hospital of Philadelphia
Funder Type Other
Recruitment Status
Enrollment Count 12 (ESTIMATED)
Results Posted Not Available

Therapy Information


Target Gene/Variant HBB
Therapy Type Gene transfer
Therapy Route Ex-vivo
Mechanism of Action Functional gene replacement
Route of Administration Intravenous
Drug Product Type Autologous cells
Target Tissue/Cell CD34+ cells
Delivery System Viral transduction
Vector Type LV
Editor Type none
Dose 1 Transduced CD34+ cells

Study Record Dates


Current Stage Phase1, Phase2
Submit Date 2024-03-26
Completion Date 2027-12-31
Last Update 2026-02-23

Participation Criteria


Eligible Age 18 Years - 35 Years
Standard Ages Adult
Sexes Eligible for Study ALL
Eligibility Criteria
Inclusion Criteria: 1. Age 18 to \< 36 years at the time of consent 2. Diagnosis of transfusion dependent beta thalassemia (β0 β0, β+β0, β+β+, βEβ0, βEβ+,β0 or β+ /βA + alpha triplication(s)). Transfusion-dependent is defined as a history of receiving at least 120 mL/kg/year packed red blood cells or at least 8 transfusions per year in the past two years. The first 2 subjects enrolled must have a non- β0 β0 genotype. 3. Genetic confirmation of α and β thalassemia diagnosis (β0β0, β+β0, β+β+, βEβ0, βEβ+, β0 or β+ /βA + alpha triplication(s)) by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory is required. 4. Clinically stable, Karnofsky score at least 70, and eligible to undergo Hematopoietic Stem Cell Transplantation (HSCT). 5. Female subjects of childbearing potential must agree to use acceptable method(s) of contraception from consent through at least 6 months after CHOP-ALS20 infusion 6. Male subjects of reproductive capacity must agree to use effective contraception from start of mobilization through at least 6 months after CHOP-ALS20 infusion 7. All potential treatment options including allogeneic HSCT (HLA-matched related, HLA-matched unrelated, and haploidentical) as well as FDA approved gene therapy options have been thoroughly discussed with the independent hematologist and/or transplant physician and subject agrees to proceed with this clinical trial. Exclusion Criteria: 1. Prior receipt of HSCT or gene therapy 2. More than one alpha globin gene deletions/mutations. 3. Any prior or current malignancy (excluding adequately treated basal or squamous cell carcinoma of the skin) 4. Known cancer predisposition syndrome 5. Positive for HIV-1, HIV-2, Human T Cell Lymphotropic Virus-1,2 (HTLV-1, HTLV-2) or active hepatitis B or active hepatitis C infection 6. Clinically significant active bacterial, viral (including COVID-19 and influenza), fungal, or parasitic infection (temporary exclusion) 7. Clinically significant bleeding disorder 8. Evidence of cardiac dysfunction (left ventricular ejection fraction \<50% or shortening fraction \<27%) or clinically significant arrhythmia 9. Evidence of advanced liver disease (ALT \>5x the upper limit of normal (ULN), prothrombin time \>1.5 x ULN, direct bilirubin \> 3x ULN) not attributable to iron chelation therapy, or evidence of bridging fibrosis on liver biopsy or fibrosis stage of F3 or higher by magnetic resonance elastography (MRE) if obtained as part of clinical care 10. Liver R2 or R2 MRI or liver biopsy with liver iron concentration 15 mg/g dw (temporary exclusion) 11. Diffusion capacity of the lungs for carbon monoxide (DLco) \<50% of predicted (corrected for Hb) 12. Pulse oximetry in room air \<92% 13. Evidence of renal dysfunction (creatinine \>1.5x ULN or Glomerular Filtration Rate (GFR) \<70 ml/min/1.73 m2 based on cystatin C/creatinine equation) 14. Cardiac T2 MRI \< 10 ms 15. Platelet count \<100,000/mcL or absolute neutrophil count \<1000/mcL except if attributed to benign ethnic neutropenia 16. Unable to receive red cell transfusion (significant allo/auto immunization) 17. Uncontrolled systemic hypertension 18. Uncontrolled seizure disorder 19. Diagnosis of a significant psychiatric disorder that could seriously impede the ability to participate in the study as determined by the investigator 20. Immediate family member with a known or suspected Familial Cancer Syndrome 21. Contraindication to anesthesia 22. For female subjects, pregnancy or breastfeeding 23. Participation in another clinical trial of an investigational drug within 30 days or 5 drug half-lives, whichever is longer, of screening (temporary exclusion) 24. Any other condition that would render the subject ineligible for mobilization/apheresis and/or HSCT as determined by the investigator
View Inclusion and Exclusion Criteria at ClinicalTrials.gov

Locations


No.of Trial Sites 1
Locations United States

Regulatory Information


Has US IND True
FDA Designations
Recent Updates

Resources/Links