Base-edited Autologous Hematopoietic Stem Cell Transplantation in Treating Patients With β-thalassemia Major

Fudan University

Status and phase

Active, not recruiting

Early Phase 1

Conditions

Beta-Thalassemia

Treatments

Biological: CS-101 injection

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT06065189

CS-101-03

Details and patient eligibility

About

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.

Full description

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.

Enrollment

5 estimated patients

Sex

All

Ages

3 to 17 years old

Volunteers

No Healthy Volunteers

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