base-edited autologous hematopoietic stem cell transplantation in treating patients with β-thalassemia major

Conditions: Beta-Thalassemia

Summary: the goal of this open label, single-arm clinical study is to learn about the safety and efficacy of base-edited autologous hematopoietic stem cell transplantation(cs-101) in treating patients with β-thalassemia major.

cs-101 is an autologous cd34+ cell suspension modified by ex vivo base editing technology, removing the inhibitory effect of bcl11a on the γ-globin coding gene, inducing the production of γ-globin chains, increasing the concentration of fetal hemoglobin (hbf) in the blood, compensating for the loss of adult hemoglobin (hba) to treat transfusion-dependent type/ major β - thalassemia. the therapy addresses two major challenges in the treatment of the disease: lack of matching donors and graft-versus-host responses commonly seen in allogeneic hematopoietic stem cell transplantation. the study consists of the following five phases: screening phase: sign informed consent, complete screening assessments, and confirm the eligibility for enrollment; baseline: check the subject's baseline status; mobilization, collection and manufacturing phase: mobilize, collect autologous cd34+ cells and manufacture, release and transport cs-101 product; conditioning and treatment phase: including myeloablation and cs-101 product infusion; follow-up phase: 180 days post-infusion.

Eligibility criteria:
inclusion criteria: * 3 to 17 years old(inclusive) male or female subjects at the time of informed consenting * diagnosis of β-thalassemia, genotypes include but are not limited to β+β0, βeβ0, β0β0, etc * generally in good condition, karnofsky performance score≥60 points for subjects≥16 years old at the time of autologous hematopoietic stem cell collection, or lansky play-performance score≥60 points for subjects under 16 years old, or equivalent clinical evaluation as the investigator site's common practice * for female subjects of childbearing potential: use effective contraceptive measures for at least 1 month prior to screening and agree to continue using such measures for contraception throughout the study * for male subjects who have a potential ability to father a child: use condoms or other methods continuously from the start of mobilization to ensure effective contraception for sexual partners during the study period exclusion criteria: * treatment with other investigational medications or other experimental interventions 30 days prior to signing informed consent or within 6 half-lives of the drug, whichever is longer. * subjects who have received or are receiving thalidomide and/or luspatercept, when their drug-drug interaction on the efficacy and safety of cs-101 cannot be ruled out, unless at least there are 3 test results showing the total hemoglobin level before transfusion is below 9g/dl in the past 6 months before screening. * previously received allogeneic hematopoietic stem cell transplantation or gene(edited) therapy. * subjects have available related fully matching donors and are eligible and prepared for allogeneic hematopoietic stem cell transplantation. * subjects with coexisting α-thalassemia and more than 2 deletions or non-deletional mutations in the α-globin chain coding genes. * known to be allergic to drugs used during autologous hematopoietic stem cell transplantation (including but not limited to granulocyte colony-stimulating factor, busulfan, dextran), excipients(such as dimethyl sulfoxide), or instruments(such as intravenous catheters) as determined by the investigator are deemed unsuitable to participate in this study. * those with active infections, including but not limited to: hiv, hepatitis b, hepatitis c, cytomegalovirus, epstein-barr virus and treponema pallidum test positive, or known tuberculosis, parasitic infection, etc. who are judged by the investigator to be unsuitable to participate in this study * echocardiography results with ejection fraction below 45% * subjects who are febrile (temperature over 37.3° c) should be held back from enrolment. * advanced liver disease, defined as aspartate aminotransferase (ast), alanine aminotransferase (alt) \>3 × upper limit of normal (uln) or baseline international normalized ratio (inr) \>1.5 × uln * mri during the screening period showed heavy iron overload and is judged by the investigator to be unable to participate in the study. * patients with past/present history of cancer * known neurological disorders, psychological problems or mental illness, and is judged by the investigator to be unable to cooperate with the study procedures * known history of uncontrolled epileptic seizures and is judged by the investigator to be unfit to participate in this study * known history of other serious cardiovascular, pulmonary, renal diseases, digestive tract conditions, liver diseases and / or other conditions, etc., and are judged by the investigator to be intolerable or inappropriate for autologous hematopoietic stem cell mobilization, collection, and myeloablative conditioning and infusion * pregnant or lactating women