Relmacabtagene Autoleucel As Second-Line Therapy in Adult Patients with Aggressive B-cell NHL

Shanghai Ming Ju Biotechnology

Status and phase: Active, not recruiting; Phase 2

Conditions: High-grade B-cell Lymphoma; Lymphoma, Large B-Cell, Diffuse; Mediastinal B-Cell Diffuse Large Cell Lymphoma; Follicular Lymphoma Grade 3B

Treatments: Biological: Relmacabtagene Autoleucel; Drug: Cyclophosphamide; Drug: Fludarabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT06093841

JWCAR029216

Details and patient eligibility

About

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.

Full 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.

Enrollment: 46 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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46 participants in 1 patient group

Relmacabtagene Autoleucel

Experimental group

Description:

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.

Treatment:

Drug: Fludarabine

Drug: Cyclophosphamide

Biological: Relmacabtagene Autoleucel