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

An Open-Label, Single-Arm Study of Relma-cel, CD19-targeted Chimeric Antigen Receptor (CAR)T Cells for Relapsed and Refractory (R/R) LBCL

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Lymphoma, Non-Hodgkin; Diffuse Large B Cell Lymphoma
• Intervention / Treatment: Biological: CD19-targeted Chimeric Antigen Receptor(CAR) T Cells

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 Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Cancer Hospital

Participation Criteria

Eligibility Criteria

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

Description

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 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
Experimental: Relma-cel; The PK, safety and efficacy of Relma-cel will be evaluated in 1 x 10^8 CAR+T cells dose level	Biological: CD19-targeted Chimeric Antigen Receptor(CAR) T Cells; Relma-cel be administered at one dose level:1×10^8 CAR+T cells

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Shanghai Ming Ju Biotechnology Co., Ltd.
• Investigators: Principal Investigator: Huilai Zhang, Tianjin Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2023
• Primary Completion (Estimated): October 30, 2024
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: November 14, 2023
• First Submitted That Met QC Criteria: November 19, 2023
• First Posted (Actual): November 28, 2023

Study Record Updates

• Last Update Posted (Actual): August 21, 2024
• Last Update Submitted That Met QC Criteria: August 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Chimeric antigen receptor; Relapsed/Refractory; B-Cell Malignancies; CAR T cells; JWCAR029
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: JWCAR029-017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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