Gene therapy trials for β-thalassemia
| Trial name . | Study design . | Inclusion criteria . | Exclusion criteria . | Intervention . | Comparison . | Outcome . |
|---|---|---|---|---|---|---|
| NorthStar Hgb 2042,6 | Phase 1/2 N = 19 Multisite | TDT age 12-35 years Any genotype | Severe iron overload Prior transplant | Beti-cel | Standard of care: Transfusion dependence and chelation | Transfusion independence for 24 months in 61% |
| Hgb2052,6 | Phase 1/2 Single site (Paris) N = 4 | TDT Age 5-35 years Any genotype | Malignancy Organ damage Infection Neutropenia | Beti-cel | Standard of care: Transfusion dependence and chelation | Transfusion independence for 24 months in 75% |
| Northstar 2 Hgb 2072,3 | Phase 3 N = 23 Multisite | TDT Age <50 years Non-β0/β0 genotype | β0/β0 genotype Known HLA match | Beti-cel | Standard of care: Transfusion dependence and chelation | Transfusion independence in 91% |
| Northstar 3 Hgb 2122,3 | Phase 2 Multisite N = 23 | TDT β0/β0, β0/β+ IVS-I-110, and β+ IVS-I-110/β+ IVS-I-110 genotypes Age <50 years | Presence of a mutation characterized as other than β0 (eg, β+, βE, βC) on at least 1 β-globin gene (HBB) allele | Beti-cel | Standard of care: Transfusion dependence and chelation | Transfusion independence in 86% |
| LTF-3032,8 | Multiphase Multisite N = 41 | TDT Previously treated with beti-cel | None | Follow-up after beti-cel 13 years | Standard of care: Transfusion dependence and chelation | Transfusion and chelation independence in 68% in phase 1/2 and 89% in phase 3 |
| β-Thalassemia Major With Autologous CD34+ Hematopoietic Progenitor Cells Transduced With TNS9.3.55 a Lentiviral Vector Encoding the Normal Human β-Globin Gene1,9 | Phase 1 Multisite N = 4 | TDT of any genotype | Infection Diabetes Myelodysplasia | Autologous CD34+ HSPCs transduced with TNS9.3.55, a lentiviral vector encoding the normal human β-globin gene Reduced-intensity busulfan | Standard of care: Transfusion dependence and chelation | Transfusion requirements reduced by 50% |
| GLOBE1,10 | Phase 1/2 N = 7 | TDT of any genotype Age >3 years | If age <18 years with an HLA match | GLOBE lentiviral vector–transduced CD34+ cells | Standard of care: Transfusion dependence and chelation | Three adults with reduced transfusion requirements Four pediatric patients with transfusion independence |
| CLIMB-THAL 1111,4 | Phase 1/2 | TDT of any genotype Age 3-64 years | Infection Malignancy | Autologous CRISPR-Cas9–edited CD34+ HSPCs | Standard of care: Transfusion dependence and chelation | 42/44 = 95% transfusion independence 2/44 = 5% reduced transfusion requirements |
| Trial name . | Study design . | Inclusion criteria . | Exclusion criteria . | Intervention . | Comparison . | Outcome . |
|---|---|---|---|---|---|---|
| NorthStar Hgb 2042,6 | Phase 1/2 N = 19 Multisite | TDT age 12-35 years Any genotype | Severe iron overload Prior transplant | Beti-cel | Standard of care: Transfusion dependence and chelation | Transfusion independence for 24 months in 61% |
| Hgb2052,6 | Phase 1/2 Single site (Paris) N = 4 | TDT Age 5-35 years Any genotype | Malignancy Organ damage Infection Neutropenia | Beti-cel | Standard of care: Transfusion dependence and chelation | Transfusion independence for 24 months in 75% |
| Northstar 2 Hgb 2072,3 | Phase 3 N = 23 Multisite | TDT Age <50 years Non-β0/β0 genotype | β0/β0 genotype Known HLA match | Beti-cel | Standard of care: Transfusion dependence and chelation | Transfusion independence in 91% |
| Northstar 3 Hgb 2122,3 | Phase 2 Multisite N = 23 | TDT β0/β0, β0/β+ IVS-I-110, and β+ IVS-I-110/β+ IVS-I-110 genotypes Age <50 years | Presence of a mutation characterized as other than β0 (eg, β+, βE, βC) on at least 1 β-globin gene (HBB) allele | Beti-cel | Standard of care: Transfusion dependence and chelation | Transfusion independence in 86% |
| LTF-3032,8 | Multiphase Multisite N = 41 | TDT Previously treated with beti-cel | None | Follow-up after beti-cel 13 years | Standard of care: Transfusion dependence and chelation | Transfusion and chelation independence in 68% in phase 1/2 and 89% in phase 3 |
| β-Thalassemia Major With Autologous CD34+ Hematopoietic Progenitor Cells Transduced With TNS9.3.55 a Lentiviral Vector Encoding the Normal Human β-Globin Gene1,9 | Phase 1 Multisite N = 4 | TDT of any genotype | Infection Diabetes Myelodysplasia | Autologous CD34+ HSPCs transduced with TNS9.3.55, a lentiviral vector encoding the normal human β-globin gene Reduced-intensity busulfan | Standard of care: Transfusion dependence and chelation | Transfusion requirements reduced by 50% |
| GLOBE1,10 | Phase 1/2 N = 7 | TDT of any genotype Age >3 years | If age <18 years with an HLA match | GLOBE lentiviral vector–transduced CD34+ cells | Standard of care: Transfusion dependence and chelation | Three adults with reduced transfusion requirements Four pediatric patients with transfusion independence |
| CLIMB-THAL 1111,4 | Phase 1/2 | TDT of any genotype Age 3-64 years | Infection Malignancy | Autologous CRISPR-Cas9–edited CD34+ HSPCs | Standard of care: Transfusion dependence and chelation | 42/44 = 95% transfusion independence 2/44 = 5% reduced transfusion requirements |
HLA, human leukocyte antigen; HSPC, hematopoietic stem cells; TDT, transfusion-dependent thalassemia.