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

Sponsor

Shanghai Ming Ju Biotechnology Co., Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT06149169

Collaborator

(none)

Enrollment

Location

Arm

19.4

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Non-Hodgkin Diffuse Large B Cell Lymphoma	Biological: CD19-targeted Chimeric Antigen Receptor(CAR) T Cells	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 17, 2023

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Mar 31, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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)-Tmax of Relma-cel [up to 1 year after Relma-cel infusion]
Time to maximum 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

Objective response rate (ORR) in LBCL subjects [3 months]
Objective response rate (ORR) in 3 month evaluated by investigator of LBCL subjects.
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.
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.
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.
Progression-free survival (PFS) [up to 1 year after Relma-cel infusion]
Progression-free survival
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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.