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

• Sponsor: Shanghai Ming Ju Biotechnology Co., Ltd. (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT06093841
• Collaborator: (none)
• Enrollment: 46
• Locations: 13
• Arm: 1
• Anticipated Duration (Months): 39
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Large B-Cell, Diffuse; Follicular Lymphoma Grade 3B; High-grade B-cell Lymphoma; Mediastinal B-Cell Diffuse Large Cell Lymphoma	Biological: Relmacabtagene Autoleucel; Drug: Fludarabine; Drug: Cyclophosphamide	Phase 2

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 46 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Relmacabtagene Autoleucel as Second-Line Therapy in Adult Patients With Aggressive B-cell NHL: a Single-arm, Multicenter, Open, Phase II Study
• Anticipated Study Start Date: Nov 1, 2023
• Anticipated Primary Completion Date: Aug 1, 2024
• Anticipated Study Completion Date: Feb 1, 2027

Arms and Interventions

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.

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

Outcome Measures

Primary Outcome Measures

1. ORR at 3 month [3 months]

   Percentage of participants with CR [CMR;CRR] or PR [partial metabolic response (PMR);

Secondary Outcome Measures

1. CRR at 3 month [3 months]

   Complete response rate in subjects at 3 month

2. 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.

3. 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.

4. 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.

5. Time to response (TTR) [up to 2 years after Relmacabtagene Autoleucel infusion]

   Time from JWCAR029 infusion to first documentation of CR or PR

6. 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.

7. 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.

8. Adverse events (AEs) [up to 2 year after Relmacabtagene Autoleucel infusion]

   Types, frequency, and severity of adverse events and laboratory anomalies Physiological parameter

9. Pharmacokinetic (PK)- Cmax of Relmacabtagene Autoleucel [up to 1 year after Relmacabtagene Autoleucel infusion]

   Maximum observed concentration of Relmacabtagene Autoleucel in peripheral blood

10. Pharmacokinetic (PK)- Tmax of Relmacabtagene Autoleucel [up to 1 year after Relmacabtagene Autoleucel infusion]

    Time to maximum concentration of Relmacabtagene Autoleucel in peripheral blood

11. Pharmacokinetic (PK)- AUC of Relmacabtagene Autoleucel [up to 1 year after Relmacabtagene Autoleucel infusion]

    Area under the concentration vs time curve of Relmacabtagene Autoleucel

12. The concentration of Car-T cell [up to 1 year after Relmacabtagene Autoleucel infusion]

    The concentration of Car-T cell in peripheral blood

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sun Yat-sen University Cancer Hospital	Guangzhou	Guangdong	China
2	Henan Cancer Hospital	Zhengzhou	Henan	China
3	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan	China
4	Hunan Cancer Hospital	Changsha	Hunan	China
5	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu	China	215006
6	Shandong Cancer Hospital	Jinan	Shandong	China
7	Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,	Shanghai	Shanghai	China	200025
8	Institute of Hematology&Hospital of Blood Disease CAMS	Tianjin	Tianjin	China	300000
9	Tianjin Cancer Hospital	Tianjin	Tianjin	China
10	The First Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang	China
11	Beijing Tongren Hospital	Beijing		China
12	Peking Union Medical College Hospital	Beijing		China
13	Jiangsu Provincial People's Hospital	Nanjing		China

Sponsors and Collaborators

• 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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shanghai Ming Ju Biotechnology Co., Ltd.
• ClinicalTrials.gov Identifier: NCT06093841
• Other Study ID Numbers: JWCAR029216
• First Posted: Oct 23, 2023
• Last Update Posted: Oct 25, 2023
• Last Verified: Oct 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Shanghai Ming Ju Biotechnology Co., Ltd.: Relmacabtagene Autoleucel; aggressive B-cell non-Hodgkin lymphoma; Chimeric antigen receptor T cells; second-line
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse; Aggression; Cyclophosphamide; Fludarabine

Study Results

No Results Posted as of Oct 25, 2023