Clinical trial NCT06093841: Relmacabtagene Autoleucel As Second-Line Therapy in Adult Patients with Aggressive B-cell NHL
Official title: Relmacabtagene Autoleucel As Second-Line Therapy in Adult Patients with Aggressive B-cell NHL: a Single-arm, Multicenter, Open, Phase II Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Lymphoma, Large B-Cell, Diffuse
Follicular Lymphoma Grade 3B
High-grade B-cell Lymphoma
Mediastinal B-Cell Diffuse Large Cell Lymphoma
Keywords: Relmacabtagene Autoleucel
aggressive B-cell non-Hodgkin lymphoma
Chimeric antigen receptor T cells
second-line
Lead sponsor: Shanghai Ming Ju Biotechnology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-10-23
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: ORR at 3 month
timeFrame: 3 months
Secondary outcomes:
measure: CRR at 3 month
timeFrame: 3 months
measure: Duration of response (DOR)
timeFrame: up to 2 years after Relmacabtagene Autoleucel infusion
measure: Duration of complete remission (DoCR)
timeFrame: up to 2 years after Relmacabtagene Autoleucel infusion
measure: Duration of partial remission (DoPR)
timeFrame: up to 2 years after Relmacabtagene Autoleucel infusion
measure: Time to response (TTR)
timeFrame: up to 2 years after Relmacabtagene Autoleucel infusion
measure: Progression-Free Survival (PFS)
timeFrame: up to 2 years after Relmacabtagene Autoleucel infusion
measure: Overall Survival (OS)
timeFrame: up to 2 year after Relmacabtagene Autoleucel infusion
measure: Adverse events (AEs)
timeFrame: up to 2 year after Relmacabtagene Autoleucel infusion
measure: Pharmacokinetic (PK)- Cmax of Relmacabtagene Autoleucel
timeFrame: up to 1 year after Relmacabtagene Autoleucel infusion
measure: Pharmacokinetic (PK)- Tmax of Relmacabtagene Autoleucel
timeFrame: up to 1 year after Relmacabtagene Autoleucel infusion
measure: Pharmacokinetic (PK)- AUC of Relmacabtagene Autoleucel
timeFrame: up to 1 year after Relmacabtagene Autoleucel infusion
measure: The concentration of Car-T cell
timeFrame: up to 1 year after Relmacabtagene Autoleucel infusion
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Hospital
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Shanghai
country: China
facility: Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,
state: Shanghai
city: Tianjin
country: China
facility: Institute of Hematology&Hospital of Blood Disease CAMS
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
city: Beijing
country: China
facility: Beijing Tongren Hospital
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Nanjing
country: China
facility: Jiangsu Provincial People's Hospital
Study officials:
affiliation: Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,
name: Weili Zhao, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of Soochow University
name: Depei Wu, PhD
role: PRINCIPAL_INVESTIGATOR
References: