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

Lymphoma, Non-Hodgkin Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06149169
• Other study ID #: JWCAR029-017
• Status: Recruiting
• Phase: Phase 2
• Start date: August 17, 2023
• Est. completion date: March 31, 2025

Study information

• Verified date: March 2024
• Source: Shanghai Ming Ju Biotechnology Co., Ltd.
• Contact: Relma-cel Medical
• Phone: +86 21 50464201
• Email: JWCAR029Medical[@]jwtherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: March 31, 2025
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• CD19-targeted Chimeric Antigen Receptor(CAR) T Cells
Relma-cel be administered at one dose level:1×10^8 CAR+T cells

Locations

Country	Name	City	State
China	Tianjin Cancer Hospital	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Ming Ju Biotechnology Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic(PK)-Cmax of Relma-cel	Maximum observed concentration of Relma-cel in peripheral blood	up to 1 year after Relma-cel infusion
Primary	Pharmacokinetic(PK)-Tmax of Relma-cel	Time to maximum concentration of Relma-cel in peripheral blood	up to 1 year after Relma-cel infusion
Primary	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	Objective response rate (ORR) in LBCL subjects	Objective response rate (ORR) in 3 month evaluated by investigator of LBCL subjects.	3 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Progression-free survival (PFS)	Progression-free survival	up to 1 year after Relma-cel infusion
Secondary	Overall survival (OS)	Overall survival	up to 1 year after Relma-cel infusion
Secondary	Changes of serum cytokines-IL-2,IL-6,IL-8 and IFN- ?	The changes of serum cytokines-IL-2,IL-6,IL-8 and IFN- ? after Relma-cel infusion.	up to 1 year after Relma-cel infusion
Secondary	Changes of inflammation biomarker-CRP	The changes of inflammation biomarker-CRP after Relma-cel infusion.	up to 1 year after Relma-cel infusion
Secondary	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