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

NCT06231368 | Active Not Recruiting Phase 1

• 1 other identifier: IIT2024003
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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

Keywords

Autoimmune Hemolytic Anemia; CNCT19 CAR T-Cell therapy

Outcome Measures

Primary Outcomes (1)

• Incidence and the severity of the adverse event

  Use Common Terminology Criteria for Adverse Events (CTCAE) Version 5 to assess the adverse event

  Within 12 months

Secondary Outcomes (1)

• Percentage of patients with hematological response

  Within 24 weeks

Study Arms (1)

CNCT19 CAR T-Cell Therapy

EXPERIMENTAL

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.

Biological: CNCT19 CAR-T cell therapy

Interventions

CNCT19 CAR-T cell therapy BIOLOGICAL

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

CNCT19 CAR T-Cell Therapy

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead
• Juventas Cell Therapy Ltd.: collaborator

Study Sites (1)

Regenerative Medicine Center

Tianjin, Tianjin Municipality, China

Location

Related Publications (1)

• Li R, Pan H, Zhang L, Ma J, Li W, Gao Z, Fang L, Tian L, Shen Y, Yang F, Zhao J, Nie N, Li J, Wang W, Pan X, Lian Y, Li X, Peng G, Li L, Yu X, Xu C, Liu Y, Kuang Z, Huang J, Zhao X, Ge M, Liu L, Chen S, Feng Y, Chang AH, Deng B, Dai M, Huang L, Lv L, Zheng Y, Luo Y, Xiong H, Shi J. CD19 CAR T-Cell Therapy for Autoimmune Hemolytic Anemia. N Engl J Med. 2026 Jan 15;394(3):253-267. doi: 10.1056/NEJMoa2509820.

  PMID: 41534043 DERIVED

MeSH Terms

Conditions

Anemia, Hemolytic, Autoimmune

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2024
• First Posted: January 30, 2024
• Study Start: February 4, 2024
• Primary Completion: November 18, 2024
• Study Completion: August 31, 2025
• Last Updated: May 16, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)