Diffuse Large B Cell Lymphoma, Lymphoma, Non-Hodgkin
Conditions
Keywords
JWCAR029, B-Cell Malignancies, CAR T cells, Chimeric antigen receptor, Relapsed/Refractory
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.
Interventions
BIOLOGICALCD19-targeted Chimeric Antigen Receptor(CAR) T Cells
Relma-cel be administered at one dose level:1×10\^8 CAR+T cells
Sponsors
Shanghai Ming Ju Biotechnology Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Objective response rate (ORR) in LBCL subjects | 3 months | Objective response rate (ORR) in 3 month evaluated by investigator of LBCL subjects. |
| 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. |
| Overall survival (OS) | up to 1 year after Relma-cel infusion | Overall survival |
| 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. |
Countries
China
Outcome results
None listed