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

Study Overview
=================
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.

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

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

Intervention / Treatment
-----------------
* Biological: CD19-targeted Chimeric Antigen Receptor(CAR) T Cells


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥18 years old; Sign on the informed consent; Subjects must have histologically confirmed Large B-cell Lymphoma; 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); Subjects have accessible PET-positive lesion and have measurable CT-positive lesion according to Lugano Classification; Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1; Adequate organ function; Adequate vascular access for leukapheresis procedur; Subjects who have previously received CD19 targeted therapy must confirm that lymphoma lesions still expresss CD19; Women of childbearing potential must agree to use highly effective methods of contraception for 1 year after the last dose of Relma-cel; 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: Central nervous system(CNS) only involvement by malignancy or primary CNS lymphoma; History of another primary malignancyn that has not been in remission for at least 2 years; Subjects has HBV,HCV,HIV or syphilis nefection at the time of screening; Active deep venous thrombosis(DVT)/Pulmonary embolism(PE),or active DVT/PE requires anti-coagulation within 3 months prior to signing the ICF; Subjects with uncontrolled systemic fungal,bacterial,viral or other infection; Presence of acute or chronic graft-versus-host disease(GVHD); History of any serious cardiovascular disease or presence of clinically relevant CNS pathology; Pregnant or nursing woman; 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; Uncontrolled conditions or unwillingness or inability to follow the procedures required in the protocol; Received CAR T-cell or other genetically-modified T-cell therapy previously.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Relma-cel<br>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<br>* Relma-cel be administered at one dose level:1×10^8 CAR+T cells<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
JWCAR029, B-Cell Malignancies, CAR T cells, Chimeric antigen receptor, Relapsed/Refractory