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

Overview

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.

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.

Interventions

• 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 w

Primary outcome measures

• Safety indicators [Time frame: 6 months after CAR-T infusion]

Secondary outcome measures (7)

• Efficacy indicators [Time frame: Three months after treatment]
• Efficacy indicators [Time frame: Three months after treatment]
• Efficacy indicators [Time frame: Three months after treatment]
• Efficacy indicators [Time frame: Three months after treatment]
• Cellular Metabolic Kinetics Indicators [Time frame: On the fourth, seventh, tenth, fourteenth, twenty-first, and twenty-eighth days after retransfusion]
• Cellular Metabolic Kinetics Indicators [Time frame: Peripheral blood CAR copy number of research participants during follow-up]
• Cellular Metabolic Kinetics Indicators [Time frame: 28 days after treatment]

Eligibility criteria

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:

• Creatinine ≤ 1.5 × ULN;
• Left ventricular ejection fraction ≥ 50%;
• Blood oxygen saturation > 90%;
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07539688 · IIT2025149

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗