CNCT19 for Patients With Autoimmune Hemolytic Anemia After Failure ≥3 Lines of Therapy.

NCT ID: NCT06231368

Last Updated: 2025-05-16

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-04
• Study Completion Date: 2025-08-31

Brief Summary

This is a Phase 1, single-arm, open-label, dose-escalation and dose-expansion study. The main purpose is to evaluate the safety and tolerability, efficacy of CNCT19 CAR T-cell therapy in patients with autoimmune hemolytic anemia after failure of three or more lines of therapy. Participants will receive CNCT19 cell infusion after preconditioning, and they will receive a 1-year follow-up.

Conditions

Autoimmune Hemolytic Anemia; Autologous CD19 CAR-T; Failure of Three or More Lines of Therapy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CNCT19 CAR T-Cell Therapy

Participants will receive CNCT19 cell infusion after preconditioning, and they need to be closely monitored for 24 hours following CAR-T cell infusion. Participants are advised to remain in the hospital for a minimum of 14 days following cell infusion. The duration of hospitalization and observation will be determined based on the researcher's comprehensive assessment of the subject's condition.

Group Type: EXPERIMENTAL

CNCT19 CAR-T cell therapy

Intervention Type: BIOLOGICAL

CNCT19 was a second-generation CAR T-cell with scFv derived from clone HI19α and 4-1BB/CD3-ζ costimulatory domain.

Interventions

CNCT19 CAR-T cell therapy

CNCT19 was a second-generation CAR T-cell with scFv derived from clone HI19α and 4-1BB/CD3-ζ costimulatory domain.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Subject and/or subject's legal personal representative fully understand and voluntarily sign informed consent forms
• Male or female age ≥ 12 years
• Subjects with autoimmune hemolytic anemia or Evans syndrome after Failure ≥3 lines of therapy. The Failure of ≥3 lines of therapy meets all the following conditions: Hemoglobin less than 10g/dl and symptoms of anemia; Failure of first-line corticosteroid therapy; Failure of second-line rituximab therapy; Failure of any one or more of the third-line treatments (splenectomy, cyclosporine, cyclophosphamide, azathioprine, mycophenolate mofetil, fludarabine, bortezomib, etc.)
• Female subjects of childbearing potential must have a negative Serum HCG test within 7 days before enrollment. Subjects of childbearing potential will be required to follow contraception requirements from the time of enrollment until the 1-year follow-up after cell infusion
• Laboratory tests of adequate organ function: Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×ULN; and have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and the blood oxygen saturation in a non-oxygenated state is >93%
• ECOG performance status ≤2
• Subject with a life expectancy of more than 3 months

Exclusion Criteria

• History of other lymphoproliferative neoplasms
• Secondary AIHA caused by drugs or infection
• Platelets in subjects with Evans syndrome<30×10^9/L
• Pregnant or breast-feeding subjects
• Treatment with any of the following within the noted period prior to study entry: a.anti-CD20 monoclonal antibodies <12 weeks, b.sutimlimab or other marketed biologics <5 half-lives; c.plasma exchange <4 weeks; d.post-splenectomy <12 weeks
• Previously received organ or stem cell transplantation
• History of new thrombosis or organ infarction in the past 6 months
• Diagnosis of the active stage of the connective tissue disease
• Had other inherited or acquired hemolytic diseases
• Have active infections, such as sepsis, bacteremia, fungemia, uncontrolled pulmonary infection and active tuberculosis, etc.
• Positive hepatitis B surface antigen (HBsAg) or hepatitis B e antigen (HBeAg); positive hepatitis B e antibody (HBe-Ab) or hepatitis B core antibody (HBc-Ab), and the HBV-DNA copy number is above the lower limit of the measurable capacity; positive hepatitis C (HCV) antibody; positive human immunodeficiency virus (HIV) antibody; positive syphilis test
• Received major surgery within 4 weeks before screening that was assessed by the researcher as unsuitable for enrollment
• Have malignant tumors within 5 years before enrollment, except tumors with negligible risk of metastasis or death and curable tumors, such as adequately treated cervical carcinoma in situ, cutaneous basal cell carcinoma, etc.
• Have any of the following cardiovascular diseases: a.Left ventricular ejection fraction (LVEF) ≤45%, b. presence of active heart disease or congestive heart failure (New York Heart Association [NYHA] Class III or IV)), c.severe arrhythmias requiring treatment (except atrial fibrillation, paroxysmal supraventricular tachycardia), d.QTcB interval ≥450ms for men and ≥470ms for women, e.have myocardial infarction, bypass surgery, or stent placement within the 6 months before the study, f.other heart diseases judged by the researcher to be unsuitable for enrollment
• Have a history of live attenuated vaccines within 6 weeks before enrollment
• Participate in other interventional clinical studies during CNCT19 CAR T-Cell therapy, and the drug has a half-life of <5. Subjects treated with active investigational drugs or intend to participate in another clinical trial or receive treatment other than that specified in the protocol throughout the study period
• Have a history of epilepsy or other active central nervous system diseases
• Have an allergy to the ingredients of the medicine used in this study
• Previously received CAR-T cell therapy
• Patients considered to be ineligible for the study by the investigator for reasons other than the above

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Juventas Cell Therapy Ltd.

INDUSTRY

Sponsor Role: collaborator

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Regenerative Medicine Center

Tianjin, Tianjin Municipality, China

Countries

China

Other Identifiers

IIT2024003

Identifier Type: -

Identifier Source: org_study_id