Relmacabtagene Autoleucel as Second-Line Therapy in Adult Patients With Aggressive B-cell NHL

Relmacabtagene Autoleucel as Second-Line Therapy in Adult Patients With Aggressive B-cell NHL: a Single-arm, Multicenter, Open, Phase II Study

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Lymphoma, Large B-Cell, Diffuse; High-grade B-cell Lymphoma; Follicular Lymphoma Grade 3B; Mediastinal B-Cell Diffuse Large Cell Lymphoma
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Relmacabtagene Autoleucel

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.

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Medical JWCAR029, PhD; Phone Number: +86 21 50464201; Email: JWCAR029Medical@jwtherapeutics.com

Study Locations

• China
  • Beijing, China
    • Beijing Tongren Hospital
    • Contact: Liang Wang; Email: wangliangtrhos@126.com
  • Beijing, China
    • Peking Union Medical College Hospital
    • Contact: Wei Zhang; Email: vv1223@vip.sina.com
  • Nanjing, China
    • Jiangsu Provincial People's Hospital
    • Contact: Huayuan Zhu; Email: huayuan.zhu@hotmal.com
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-sen University Cancer Hospital
      • Contact: Qingqing Cai; Email: caiqq@sysucc.org.cn
  • Henan
    • Zhengzhou, Henan, China
      • Henan Cancer Hospital
      • Contact: Keshu Zhou; Email: drzhouks77@163.com
    • Zhengzhou, Henan, China
      • The First Affiliated Hospital of Zhengzhou University
      • Contact: Mingzhi Zhang
  • Hunan
    • Changsha, Hunan, China
      • Hunan Cancer Hospital
      • Contact: Hui Zhou; Email: liyajun@hnca.org.cn
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University
      • Contact: Depei Wu, PhD; Email: drwudepei@163.com
  • Shandong
    • Jinan, Shandong, China
      • Shandong Cancer Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,
      • Contact: Weili Zhao, PhD; Email: zwl_trial@163.com
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Cancer Hospital
    • Tianjin, Tianjin, China, 300000
      • Institute of Hematology&Hospital of Blood Disease CAMS
      • Contact: Dehui Zou, PhD; Email: zoudehui@ihcams.ac.cn
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital of Zhejiang University School of Medicine
      • Contact: Jie Jin; Email: jiej0503@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: Cyclophosphamide; Administered according to package insert; Drug: Fludarabine; Administered according to package insert; Biological: Relmacabtagene Autoleucel; A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells; Other Names: JWCAR029

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR at 3 month	Percentage of participants with CR [CMR;CRR] or PR [partial metabolic response (PMR);	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	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.	up to 2 years after Relmacabtagene Autoleucel infusion
Pharmacokinetic (PK)- Cmax of Relmacabtagene Autoleucel	Maximum observed concentration of Relmacabtagene Autoleucel in peripheral blood	up to 1 year after Relmacabtagene Autoleucel infusion
Pharmacokinetic (PK)- Tmax of Relmacabtagene Autoleucel	Time to maximum concentration of Relmacabtagene Autoleucel in peripheral blood	up to 1 year after Relmacabtagene Autoleucel infusion
Pharmacokinetic (PK)- AUC of Relmacabtagene Autoleucel	Area under the concentration vs time curve of Relmacabtagene Autoleucel	up to 1 year after Relmacabtagene Autoleucel infusion
The concentration of Car-T cell	The concentration of Car-T cell in peripheral blood	up to 1 year after Relmacabtagene Autoleucel infusion
CRR at 3 month	Complete response rate in subjects at 3 month	3 months
Duration of response (DOR)	Time from first response(PR or CR) to disease progression or death from any cause.	up to 2 years after Relmacabtagene Autoleucel infusion
Duration of complete remission (DoCR)	Time from complete response (CR) to disease progression or death from any cause.	up to 2 years after Relmacabtagene Autoleucel infusion
Duration of partial remission (DoPR)	Time from partial response (PR) to disease progression or death from any cause.	up to 2 years after Relmacabtagene Autoleucel infusion
Time to response (TTR)	Time from JWCAR029 infusion to first documentation of CR or PR	up to 2 years after Relmacabtagene Autoleucel infusion
Overall Survival (OS)	OS is defined as the time from Relmacabtagene Autoleucel infusion to the date of death from any cause.	up to 2 year after Relmacabtagene Autoleucel infusion
Adverse events (AEs)	Types, frequency, and severity of adverse events and laboratory anomalies Physiological parameter	up to 2 year after Relmacabtagene Autoleucel infusion

Collaborators and Investigators

• Sponsor: Shanghai Ming Ju Biotechnology Co., Ltd.
• Investigators: Principal Investigator: Weili Zhao, PhD, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,; Principal Investigator: Depei Wu, PhD, The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2023
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: October 16, 2023
• First Submitted That Met QC Criteria: October 16, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): October 25, 2023
• Last Update Submitted That Met QC Criteria: October 24, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: second-line; Chimeric antigen receptor T cells; Relmacabtagene Autoleucel; aggressive B-cell non-Hodgkin lymphoma
• Additional Relevant MeSH Terms: Behavioral Symptoms; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Aggression; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: JWCAR029216

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No