Follicular Lymphoma Grade 3B, High-grade B-cell Lymphoma, Lymphoma, Large B-Cell, Diffuse, Mediastinal B-Cell Diffuse Large Cell Lymphoma
Conditions
Keywords
Relmacabtagene Autoleucel, aggressive B-cell non-Hodgkin lymphoma, Chimeric antigen receptor T cells, second-line
Brief summary
The primary objective of this study is to asess the efficacy of Relmacabtagene autoleucel as second-line therapy in adult patients with aggressive B-cell Non-Hodgkins Lymphoma who are ineligible for haematopoietic stem cell transplantation.
Detailed description
This is an open-label, multicenter, Phase 2 study to determine the antitumor activity, PK, and safety of JWCAR029(Relmacabtagene autoleucel ) in subjects who have relapsed within 12 months from, or are refractory to, a single line of immunochemotherapy for aggressive Bcell NHL and are ineligible for HSCT (as defined in the eligibility criteria). Subjects will be treated with lymphodepleting chemotherapy and JWCAR029.
Interventions
BIOLOGICALRelmacabtagene Autoleucel
A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells
DRUGFludarabine
Administered according to package insert
DRUGCyclophosphamide
Administered according to package insert
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. Age≥18 years; 2. Signed written informed consent obtained prior to any study procedures; 3. Histologically confirmed relapsed or refractory (R/R) aggressive B-cell NHL of the following histologiesLBCL as defined by the World Health Organization (WHO) Classification 2022:Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), high-grade B-cell lymphoma (HGL) with MYC and BCL2 rearrangements,HGL-NOS, Primary mediastinal large B-cell lymphoma, Follicular lymphoma Grade 3B (FL3B),Indolent B-NHL-transformed large B-cell lymphoma with adequate prior treatment with anthracycline-containing agents and rituximab or other CD20-targeted agents; 4. Subjects must meet the definition of refractory or relapsed; 5. Subjects were not eligible for HDCT/ASCT based on the investigator's assessment ; 6. Adequate organ function; 7. Presence of positive PET assessable lesions as determined by the Lugano criteria ; 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; 9. Expected survival greater than 12 weeks; 10. Adequate vascular access for leukapheresis procedure; 11. Women of childbearing potential must agree to use highly effective methods of contraception for at least 28 days prior to lymphocyte clearance chemotherapy through 2 year after Relmacabtagene Autoleucel infusion; Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method for 2 year after Relmacabtagene Autoleucel infusion;
Exclusion criteria
1. Subjects with non-Hodgkin's lymphoma who have received second or more line therapy; 2. Lymphoma of the primary center (subjects with secondary central nervous system lymphoma are allowed to enroll; 3. History of another primary malignancy that has not been in remission for at least 2 years; 4. Subjects has active HBV, HCV, HIV or syphilis infection at the time of screening; 5. Deep venous thrombosis (DVT)/Pulmonary embolism (PE), or DVT/PE requires anti-coagulation within 3 months prior to signing the ICF; 6. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection; 7. Uncontrolled diabetes and hypertension; 8. Presence of acute or chronic graft-versus-host disease (GVHD); 9. Active autoimmune disease requiring immunosuppressive therapy; 10. History of any serious cardiovascular disease or presence of clinically relevant CNS pathology; 11. Pregnant or nursing women; 12. Subjects Received an autologous or allogeneic hematopoietic stem cell transplant; 13. Uncontrolled conditions or unwillingness or inability to follow the procedures required in the protocol; 14. Received CAR T-cell or other genetically-modified T-cell therapy previously; 15. Received live vaccination within 6 weeks prior to lymphocyte clearance chemotherapy; 16. History of severe hypersensitivity reactions to any of the drug ingredients used in this study product.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR at 3 month | 3 months | Percentage of participants with CR \[CMR;CRR\] or PR \[partial metabolic response (PMR); |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | up to 2 year after Relmacabtagene Autoleucel infusion | OS is defined as the time from Relmacabtagene Autoleucel infusion to the date of death from any cause. |
| Progression-Free Survival (PFS) | up to 2 years after Relmacabtagene Autoleucel infusion | PFS is defined as the time from the Relmacabtagene Autoleucel infusion date to the date of disease progression per Lugano classification or death from any cause. |
| CRR at 3 month | 3 months | Complete response rate in subjects at 3 month |
| Duration of response (DOR) | up to 2 years after Relmacabtagene Autoleucel infusion | Time from first response(PR or CR) to disease progression or death from any cause. |
| Duration of complete remission (DoCR) | up to 2 years after Relmacabtagene Autoleucel infusion | Time from complete response (CR) to disease progression or death from any cause. |
| Adverse events (AEs) | up to 2 year after Relmacabtagene Autoleucel infusion | Types, frequency, and severity of adverse events and laboratory anomalies Physiological parameter |
| Time to response (TTR) | up to 2 years after Relmacabtagene Autoleucel infusion | Time from JWCAR029 infusion to first documentation of CR or PR |
| Pharmacokinetic (PK)- Cmax of Relmacabtagene Autoleucel | up to 1 year after Relmacabtagene Autoleucel infusion | Maximum observed concentration of Relmacabtagene Autoleucel in peripheral blood |
| Pharmacokinetic (PK)- Tmax of Relmacabtagene Autoleucel | up to 1 year after Relmacabtagene Autoleucel infusion | Time to maximum concentration of Relmacabtagene Autoleucel in peripheral blood |
| Pharmacokinetic (PK)- AUC of Relmacabtagene Autoleucel | up to 1 year after Relmacabtagene Autoleucel infusion | Area under the concentration vs time curve of Relmacabtagene Autoleucel |
| The concentration of Car-T cell | up to 1 year after Relmacabtagene Autoleucel infusion | The concentration of Car-T cell in peripheral blood |
| Duration of partial remission (DoPR) | up to 2 years after Relmacabtagene Autoleucel infusion | Time from partial response (PR) to disease progression or death from any cause. |
Countries
China
Outcome results
None listed