CD19-targeted CAR T Cells for Relapsed and Refractory (R/R) Large B-cell Lymphoma

Phase 2

Active, not recruiting

• Conditions: Diffuse Large B Cell Lymphoma; Lymphoma, Non-Hodgkin
• Interventions: Biological: CD19-targeted Chimeric Antigen Receptor(CAR) T Cells

• Registration Number: NCT06149169
• Lead Sponsor: Shanghai Ming Ju Biotechnology Co., Ltd.

Brief Summary

This is an open-label, single-arm study to treat the adult R/R Large B-cell Lymphoma subjects with Relmacabtagene autoleucel (relma-cel) in China.

Detailed Description

This is an open-label, single-arm study conducted in adult subjects with R/R LBCL in China to evaluate the pharmacokinetics(PK), safety and efficacy of relma-cel, monitor the immune response after relma-cel treatment.

Relma-cel was approved by the China National Medical Products Administration(NMPA)in September 2021(Acceptance No:CXSS2000036)for the treatment of adult patients with R/R LBCL after second-line or more systemic therapy.The recommended dose is 1×10\^8 CAR+T cells.The indication for this application is R/R LBCL(supplement study) and the recommended dose is 1×10\^8 CAR+T cells.

Study Timeline

• Study Start: 2023-08-17
• Study First Submitted: 2023-11-14
• Study First Submitted QC: 2023-11-19
• Study First Posted: 2023-11-28
• Status Verified: 2024-03
• Last Update Submitted: 2024-08-19
• Last Update Posted: 2024-08-21
• Primary Completion: 2024-10-30
• Study Completion: 2025-03-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

1. ≥18 years old;
2. Sign on the informed consent;
3. Subjects must have histologically confirmed Large B-cell Lymphoma;
4. Subjects had been treated with anthracyclines and rituximab(or other CD20-targeted antibodies) and had relapsed, failed to respond, or progressed after at least two lines of therapy include autologous hematopoietic stem cell transplantation(auto-HSCT);
5. Subjects have accessible PET-positive lesion and have measurable CT-positive lesion according to Lugano Classification;
6. Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1;
7. Adequate organ function;
8. Adequate vascular access for leukapheresis procedur;
9. Subjects who have previously received CD19 targeted therapy must confirm that lymphoma lesions still expresss CD19;
10. Women of childbearing potential must agree to use highly effective methods of contraception for 1 year after the last dose of Relma-cel;
11. Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method for 1 year after the last dose of Relma-cel.

Exclusion Criteria

1. Central nervous system(CNS) only involvement by malignancy or primary CNS lymphoma;
2. History of another primary malignancyn that has not been in remission for at least 2 years;
3. Subjects has HBV,HCV,HIV or syphilis nefection at the time of screening;
4. Active deep venous thrombosis(DVT)/Pulmonary embolism(PE),or active DVT/PE requires anti-coagulation within 3 months prior to signing the ICF;
5. Subjects with uncontrolled systemic fungal,bacterial,viral or other infection;
6. Presence of acute or chronic graft-versus-host disease(GVHD);
7. History of any serious cardiovascular disease or presence of clinically relevant CNS pathology;
8. Pregnant or nursing woman;
9. Subjects using of any chemotherapy,corticisteriod,experiment agents,GVHD therapies,radiation,allo-HSCT or any other therapies for lymphoma must go through a specific wash-out period before leukapheresis;
10. Uncontrolled conditions or unwillingness or inability to follow the procedures required in the protocol;
11. Received CAR T-cell or other genetically-modified T-cell therapy previously.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Relma-cel	CD19-targeted Chimeric Antigen Receptor(CAR) T Cells	The PK, safety and efficacy of Relma-cel will be evaluated in 1 x 10\^8 CAR+T cells dose level

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic(PK)-Tmax of Relma-cel	up to 1 year after Relma-cel infusion	Time to maximum concentration of Relma-cel in peripheral blood
Pharmacokinetic(PK)-Cmax of Relma-cel	up to 1 year after Relma-cel infusion	Maximum observed concentration of Relma-cel in peripheral blood
Pharmacokinetic(PK)-AUC of Relma-cel	up to 1 year after Relma-cel infusion	Area under the concentration vs time curve of Relma-cel

Secondary Outcome Measures

Name	Time	Method
Objective response rate (ORR) in LBCL subjects	3 months	Objective response rate (ORR) in 3 month evaluated by investigator of LBCL subjects.
Complete response rate (CRR) in LBCL subjects	up to 1 year after Relma-cel infusion	Complete response rate (CRR) at any time points evaluated by the investigator.
Best objective response rate ( Best ORR) in LBCL subjects	up to 1 year after Relma-cel infusion	Best objective response rate (ORR) evaluated by the investigator of LBCL subjects.
Adverse events (AEs)	up to 1 year after Relma-cel infusion	These adverse events would be measured by assessment scale method according to NCI-CTCAE v4.03 classification standard.
Duration of response (DOR)	up to 1 year after Relma-cel infusion	Time from first response (PR or CR) to disease progression or death from any cause.
Overall survival (OS)	up to 1 year after Relma-cel infusion	Overall survival
Changes of serum cytokines-IL-2，IL-6，IL-8 and IFN- γ	up to 1 year after Relma-cel infusion	The changes of serum cytokines-IL-2，IL-6，IL-8 and IFN- γ after Relma-cel infusion.
Changes of inflammation biomarker-CRP	up to 1 year after Relma-cel infusion	The changes of inflammation biomarker-CRP after Relma-cel infusion.
Progression-free survival (PFS)	up to 1 year after Relma-cel infusion	Progression-free survival
Changes of inflammation biomarker-serum ferritin	up to 1 year after Relma-cel infusion	The changes of inflammation biomarker-serum ferritin after Relma-cel infusion.

Trial Locations

Locations (1)

Tianjin Cancer Hospital; 🇨🇳 Tianjin, Tianjin, China