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

Autoimmune Hemolytic Anemia Clinical Trial

Official title:

The Safety and Efficacy of CNCT19 for Patients With Autoimmune Hemolytic Anemia After Failure of Three or More Lines of Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06231368
• Other study ID #: HY001010
• Status: Recruiting
• Phase: Phase 1
• Start date: February 4, 2024
• Est. completion date: August 31, 2025

Study information

• Verified date: February 2024
• Source: Institute of Hematology & Blood Diseases Hospital, China
• Contact: Jun Shi, PhD
• Phone: 13752253515
• Email: shijun[@]ihcams.ac.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6
• Est. completion date: August 31, 2025
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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 antibody 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

Related Conditions & MeSH terms

• Anemia
• Anemia, Hemolytic
• Anemia, Hemolytic, Autoimmune
• Autoimmune Hemolytic Anemia
• Hemolysis

Intervention

Biological:
• CNCT19 CAR-T cell therapy
CNCT19 was a second-generation CAR T-cell with scFv derived from clone HI19a and 4-1BB/CD3-? costimulatory domain.

Locations

Country	Name	City	State
China	Regenerative Medicine Center	Tianjin	Tianjin

Sponsors (2)

Lead Sponsor	Collaborator
Institute of Hematology & Blood Diseases Hospital, China	Juventas Cell Therapy Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percentage of patients with hematological response	Hematological response is mainly evaluated by hemoglobin (Hb), laboratory Indicators of hemolysis (serum bilirubin and lactate dehydrogenase) and blood transfusion.	Within 24 weeks