Phase I Clinical Study on the Safety and Efficacy of CY-219 CAR-T Cell Injection in the Treatment of Relapsed/Refractory B-Cell Lymphoma

This study is an open-label, single-arm, prospective clinical trial involving patients with relapsed/refractory B-cell lymphoma, aimed at evaluating the safety and efficacy of CAR-T cell infusion.

Study Overview

• Status: Not yet recruiting
• Conditions: Diffuse Large B-cell Lymphoma; Relapsed/Refractory B-cell Lymphoma; Inert B-cell Lymphoma Transformed Into Large B-cell Lymphoma (Excluding Richter Transformation, THRLBCL, and BL)
• Intervention / Treatment: Drug: CY-219 CAR-T

Detailed Description

This study is an open-label, single-arm, prospective clinical trial involving patients with relapsed/refractory B-cell lymphoma. It plans to enroll 9-18 participants and uses a "3+3" dose-escalation design (with 3 dose groups: 1×10^6, 2×10^6, and 3×10^6 CAR cells/kg) along with a dose-expansion study to administer CAR-T cell injection. Patients will be followed to observe adverse reactions and collect data on treatment efficacy, evaluating the safety and effectiveness of the CAR-T cell injection. The DLT observation period is 28 days after CAR-T cell infusion.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Liang Huang; Phone Number: 02223608359; Email: huangliang@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. The participant has given consent and signed the informed consent form, and is willing and able to comply with the planned visits, research treatments, laboratory tests, and other trial procedures;

• 2. Clinically diagnosed as a patient with relapsed/refractory B-cell lymphoma, and confirmed by pathological and histological examination as CD19 and/or CD22 B-cell lymphoma, including: diffuse large B-cell lymphoma, or transformed large B-cell lymphoma from indolent B-cell lymphoma (excluding Richter transformation, THRLBCL, BL). And meets the following criteria (meets any one of the first three items and the fourth): i. Recurrence ≥6 months after achieving remission with first-line full treatment, or ≥12 months after achieving remission following stem cell transplantation; ii. Progression during first-line treatment combined with high-risk factors (double-expressor lymphoma, double-hit lymphoma, TP53 gene mutation or deletion, IPI score ≥3); iii. Disease relapse after ≥2 lines of treatment or failure to achieve remission; iv. The participant has received the following treatment regimens after being diagnosed with LBCL:

  • Anti-CD20 monoclonal antibody;
  • Combination chemotherapy containing anthracyclines.
• 3. Age 18 or older, both men and women are eligible;
• 4. Study participants with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
• 5. Expected survival of more than 3 months from the date of signing the informed consent;
• 6. HGB ≥ 60 g/L (transfusion allowed); LYM ≥ 0.3×10^9/L;

• 7. Liver and kidney function and cardiopulmonary function must meet the following requirements:

  1. Creatinine ≤ 1.5 × ULN;
  2. Left ventricular ejection fraction ≥ 50%;
  3. Blood oxygen saturation > 90%;
  4. Total bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 2.5 × ULN;
• 8. Participants intending to become pregnant must agree to use contraception before enrollment in the study and for one year after CAR-T cell infusion; if a participant becomes pregnant or suspects pregnancy, they should immediately inform the investigator.

Exclusion Criteria:

• 1. Severe heart failure or left ventricular ejection fraction <50%;
• 2. History of severe pulmonary function impairment;
• 3. Concurrent other malignant tumors in the progressive stage;
• 4. Concurrent severe infection that cannot be effectively controlled;
• 5. Concurrent severe autoimmune disease or congenital immunodeficiency;
• 6. History of CAR-T cell immunotherapy;
• 7. Active hepatitis (hepatitis B virus deoxyribonucleic acid [HBV-DNA] or hepatitis C virus ribonucleic acid [HCV-RNA] test results above the detection limit);
• 8. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), or syphilis infection.
• 9. A history of severe allergic reactions to biological products (including antibiotics);
• 10. Allogeneic hematopoietic stem cell transplant patients who still have acute graft-versus-host disease (GvHD) one month after stopping immunosuppressive agents;
• 11. Women who are pregnant, breastfeeding, or planning to become pregnant within 12 months;
• 12. Patients with other serious physical or mental illnesses or abnormal laboratory test results that may increase the risk of participating in the study, or interfere with study results, or who are deemed by the investigators to be unsuitable for participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: CY-219 CAR-T

Drug: CY-219 CAR-T; Eligible participants should receive preconditioning 5 to 3 days before CAR-T cell infusion. The recommended preconditioning regimen is fludarabine (30 mg/m²/day, for 3 consecutive days) and cyclophosphamide (300 mg/m²/day, for 3 consecutive days) (Flu/Cy). Thirty minutes before infusion, prophylactic medication for allergic reactions should be administered: 25 mg of promethazine hydrochloride or 12.5 mg of diphenhydramine, either intramuscularly or orally. A '3+3' dose-escalation study design will be used, aiming to recruit 9-18 subjects with relapsed/refractory B-cell lymphoma.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety indicators	Six months after CAR-T infusion, analyze the recorded possible adverse reactions, mainly including the number of cases, incidence, and severity of immune-related toxicities such as cytokine release syndrome, immune effector cell-associated neurotoxicity, hematologic toxicity, and organ toxicity. The incidence of DLT.	6 months after CAR-T infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy indicators	Tumor objective response rate (ORR) at 3 months follow-up after treatment.	Three months after treatment
Efficacy indicators	Complete remission (CR) rate at 3 months post-treatment follow-up	Three months after treatment
Efficacy indicators	Overall survival (OS) at 3 months post-treatment follow-up	Three months after treatment
Efficacy indicators	Progression-free survival (PFS) at 3 months after treatment follow-up	Three months after treatment
Cellular Metabolic Kinetics Indicators	Peripheral blood CAR copy number of research participants during follow-up	On the fourth, seventh, tenth, fourteenth, twenty-first, and twenty-eighth days after retransfusion
Cellular Metabolic Kinetics Indicators	Maximum concentration (Cmax) of CAR-T cells in peripheral blood and the time to reach it	Peripheral blood CAR copy number of research participants during follow-up
Cellular Metabolic Kinetics Indicators	Area under the CAR-T expansion curve AUC0-28d over 28 days	28 days after treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
CAR-T single-cell phenotype and clonal characteristics	CY-219 CAR-T cell infusion product and the in vivo CAR-T single-cell phenotype, clonal characteristics of research participants, as well as other indicators of interest to researchers, such as cytokine profiles.	Test the product on the day of infusion. Follow-up will be conducted on day 10 and day 28 after infusion. From the 2nd month to the 3rd month, follow-up will be conducted once a month; from the 6th month to the 1st year, follow-up will be conducted once

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: February 26, 2026
• First Submitted That Met QC Criteria: April 13, 2026
• First Posted (Actual): April 20, 2026

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: IIT2025149

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No