Relmacabtagene Autoleucel As Second-Line Therapy in Adult Patients with Aggressive B-cell NHL
- Conditions
- Follicular Lymphoma Grade 3BMediastinal B-Cell Diffuse Large Cell LymphomaLymphoma, Large B-Cell, DiffuseHigh-grade B-cell Lymphoma
- Interventions
- Registration Number
- NCT06093841
- Lead Sponsor
- Shanghai Ming Ju Biotechnology Co., Ltd.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 46
- Age≥18 years;
- Signed written informed consent obtained prior to any study procedures;
- 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;
- Subjects must meet the definition of refractory or relapsed;
- Subjects were not eligible for HDCT/ASCT based on the investigator's assessment ;
- Adequate organ function;
- Presence of positive PET assessable lesions as determined by the Lugano criteria ;
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
- Expected survival greater than 12 weeks;
- Adequate vascular access for leukapheresis procedure;
- 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;
- Subjects with non-Hodgkin's lymphoma who have received second or more line therapy;
- Lymphoma of the primary center (subjects with secondary central nervous system lymphoma are allowed to enroll;
- History of another primary malignancy that has not been in remission for at least 2 years;
- Subjects has active HBV, HCV, HIV or syphilis infection at the time of screening;
- Deep venous thrombosis (DVT)/Pulmonary embolism (PE), or DVT/PE requires anti-coagulation within 3 months prior to signing the ICF;
- Subjects with uncontrolled systemic fungal, bacterial, viral or other infection;
- Uncontrolled diabetes and hypertension;
- Presence of acute or chronic graft-versus-host disease (GVHD);
- Active autoimmune disease requiring immunosuppressive therapy;
- History of any serious cardiovascular disease or presence of clinically relevant CNS pathology;
- Pregnant or nursing women;
- Subjects Received an autologous or allogeneic hematopoietic stem cell transplant;
- 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;
- Received live vaccination within 6 weeks prior to lymphocyte clearance chemotherapy;
- History of severe hypersensitivity reactions to any of the drug ingredients used in this study product.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Relmacabtagene Autoleucel Relmacabtagene Autoleucel Experimental: Relmacabtagene Autoleucel Participants will receive cyclophosphamide250 mg/m\^2/day intravenously (IV) and fludarabine 25 mg/m\^2/day IV conditioning chemotherapy for 3 days followed by Relmacabtagene Autoleucel administered as a single IV infusion at a target dose of 1 x 10\^8 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells on Day1. Relmacabtagene Autoleucel Fludarabine Experimental: Relmacabtagene Autoleucel Participants will receive cyclophosphamide250 mg/m\^2/day intravenously (IV) and fludarabine 25 mg/m\^2/day IV conditioning chemotherapy for 3 days followed by Relmacabtagene Autoleucel administered as a single IV infusion at a target dose of 1 x 10\^8 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells on Day1. Relmacabtagene Autoleucel Cyclophosphamide Experimental: Relmacabtagene Autoleucel Participants will receive cyclophosphamide250 mg/m\^2/day intravenously (IV) and fludarabine 25 mg/m\^2/day IV conditioning chemotherapy for 3 days followed by Relmacabtagene Autoleucel administered as a single IV infusion at a target dose of 1 x 10\^8 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells on Day1.
- Primary Outcome Measures
Name Time Method ORR at 3 month 3 months Percentage of participants with CR \[CMR;CRR\] or PR \[partial metabolic response (PMR);
- Secondary Outcome Measures
Name Time Method Pharmacokinetic (PK)- Cmax of Relmacabtagene Autoleucel up to 1 year after Relmacabtagene Autoleucel infusion Maximum observed concentration of Relmacabtagene Autoleucel 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.
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.
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 complete remission (DoCR) up to 2 years after Relmacabtagene Autoleucel infusion Time from complete response (CR) to disease progression 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.
Time to response (TTR) up to 2 years after Relmacabtagene Autoleucel infusion Time from JWCAR029 infusion to first documentation of CR or PR
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.
Adverse events (AEs) up to 2 year after Relmacabtagene Autoleucel infusion Types, frequency, and severity of adverse events and laboratory anomalies Physiological parameter
Trial Locations
- Locations (13)
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
Sun Yat-sen University Cancer Hospital
🇨🇳Guangzhou, Guangdong, China
Shandong Cancer Hospital
🇨🇳Jinan, Shandong, China
Tianjin Cancer Hospital
🇨🇳Tianjin, Tianjin, China
Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,
🇨🇳Shanghai, Shanghai, China
The First Affiliated Hospital of Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Peking Union Medical College Hospital
🇨🇳Beijing, China
Jiangsu Provincial People's Hospital
🇨🇳Nanjing, China
Institute of Hematology&Hospital of Blood Disease CAMS
🇨🇳Tianjin, Tianjin, China
Beijing Tongren Hospital
🇨🇳Beijing, China