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

Lymphoma, Large B-Cell, Diffuse Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06093841
• Other study ID #: JWCAR029216
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: November 2023
• Est. completion date: February 2027

Study information

• Verified date: October 2023
• Source: Shanghai Ming Ju Biotechnology Co., Ltd.
• Contact: Medical JWCAR029, PhD
• Phone: +86 21 50464201
• Email: JWCAR029Medical[@]jwtherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 46
• Est. completion date: February 2027
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Aggression
• Follicular Lymphoma Grade 3B
• High-grade B-cell Lymphoma
• Lymphoma
• Lymphoma, Large B-Cell, Diffuse

Intervention

Biological:
• Relmacabtagene Autoleucel
A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells

Drug:
• Fludarabine
Administered according to package insert
• Cyclophosphamide
Administered according to package insert

Locations

Country	Name	City	State
China	Beijing Tongren Hospital	Beijing
China	Peking Union Medical College Hospital	Beijing
China	Hunan Cancer Hospital	Changsha	Hunan
China	Sun Yat-sen University Cancer Hospital	Guangzhou	Guangdong
China	The First Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Shandong Cancer Hospital	Jinan	Shandong
China	Jiangsu Provincial People's Hospital	Nanjing
China	Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,	Shanghai	Shanghai
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Institute of Hematology&Hospital of Blood Disease CAMS	Tianjin	Tianjin
China	Tianjin Cancer Hospital	Tianjin	Tianjin
China	Henan Cancer Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Ming Ju Biotechnology Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ORR at 3 month	Percentage of participants with CR [CMR;CRR] or PR [partial metabolic response (PMR);	3 months
Secondary	CRR at 3 month	Complete response rate in subjects at 3 month	3 months
Secondary	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
Secondary	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
Secondary	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
Secondary	Time to response (TTR)	Time from JWCAR029 infusion to first documentation of CR or PR	up to 2 years after Relmacabtagene Autoleucel infusion
Secondary	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
Secondary	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
Secondary	Adverse events (AEs)	Types, frequency, and severity of adverse events and laboratory anomalies Physiological parameter	up to 2 year after Relmacabtagene Autoleucel infusion
Secondary	Pharmacokinetic (PK)- Cmax of Relmacabtagene Autoleucel	Maximum observed concentration of Relmacabtagene Autoleucel in peripheral blood	up to 1 year after Relmacabtagene Autoleucel infusion
Secondary	Pharmacokinetic (PK)- Tmax of Relmacabtagene Autoleucel	Time to maximum concentration of Relmacabtagene Autoleucel in peripheral blood	up to 1 year after Relmacabtagene Autoleucel infusion
Secondary	Pharmacokinetic (PK)- AUC of Relmacabtagene Autoleucel	Area under the concentration vs time curve of Relmacabtagene Autoleucel	up to 1 year after Relmacabtagene Autoleucel infusion
Secondary	The concentration of Car-T cell	The concentration of Car-T cell in peripheral blood	up to 1 year after Relmacabtagene Autoleucel infusion