Relmacabtagene Autoleucel as First-Line Therapy for High-Risk Large B-Cell Lymphoma

Study to Evaluate the Efficacy and Safety of Relmacabtagene Autoleucel (Relma-cel) as First-Line Therapy in Adult Participants With High-Risk Large B-Cell Lymphoma

The primary objective of this study is to estimate the efficacy of Relmacabtagene Autoleucel in participants with high-risk large B-cell lymphoma.

Study Overview

• Status: Recruiting
• Conditions: B-cell Lymphoma
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Relmacabtagene Autoleucel

Detailed Description

This is a prospective, open-label, multicenter, single-arm trial, assessed the efficacy and safety of JWCAR029(relma-cel) as part of first-line therapy after an incomplete first-line treatment regimen of two cycles of chemoimmunotherapy. High-risk LBCL was defined by the dynamic risk assessment of interim PET2+, together with either double- or triple-hit lymphomas or high-intermediate- and high-risk IPI scores (≥3). All sujects will be followed for 2 years following JWCAR029 infusion.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yuqin Song, PhD; Phone Number: +86 010-88121122; Email: songyuqin622@163.com
• Study Contact Backup: Name: Medical JWCAR029; Phone Number: +86 21 50464201; Email: JWCAR029Medical@jwtherapeutics.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100010
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Yuqin Song, PhD
    • Beijing, Beijing, China, 100010
      • Recruiting
      • Peking University International Hospital
      • Contact: Liu xinjian
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Not yet recruiting
      • Henan Cancer Hospital
      • Contact: Keshu Zhou; Email: drzhouks77@163.com
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Not yet recruiting
      • Tianjin Medical University Cancer Institute and Hospital
      • Contact: Huilai Zhang; Email: zhanghltch@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ≥ 18 years old;
2. Sign on the informed consent;
3. Histologically confirmed large B-cell lymphoma that also meets the definition of high-risk large B-cell lymphoma as a lymphoma International Prognostic Index (IPI) score of 3-5 and/or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement (double/triple-hit lymphoma) (DHL/THL) and must be treated with 2 cycles of CD20 monoclonal antibodies combined with anthracyclines. Presence of positive PET assessable lesions (DS score of 4 or 5) as determined by the Lugano criteria (Cheson et al., 2014)；
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
5. Expected survival greater than 12 weeks；

6. Adequate organ function：

   1. Absolute neutrophil count ≥ 1000/μL；Absolute lymphocyte count ≥ 100/μL； Platelet count ≥ 75,000/μL；Hb ≥ 80g/L；
   2. Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance (Cockcroft-Gault formula) > 50 mL/min (serum creatinine clearance due to lymphoma mass compression should be > 30 mL/min)；
   3. Serum alanine aminotransferase (ALT) ≤ 5 upper limit of normal (ULN) and total bilirubin ≤2ULN（or for subjects with Gilbert's syndrome or lymphoma invading the liver < 3 ULN）；
   4. Baseline oxygen saturation > 92% on room air；
   5. Left ventricular ejection fraction (LVEF) ≥50% assessed by echocardiography or radionuclide activity angiography (MUGA) within 1 month of enrollment；
7. Adequate vascular access for leukapheresis procedure;
8. Women of childbearing potential must agree to use highly effective methods of contraception for at least 28 days prior to lymphocyte clearance chemotherapy through 1 year after Relmacabtagene Autoleucel infusion; Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method for 1 year after Relmacabtagene Autoleucel infusion.

Exclusion Criteria:

1. Lymphoma involving the central nervous system (CNS)；
2. History of another primary malignancy that has not been in remission for at least 2 years;
3. History of Richter's transformation of chronic lymphocytic leukemia or primary mediastinal B-cell lymphoma；
4. Subjects has 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. Presence of acute or chronic graft-versus-host disease (GVHD);
8. History of any serious cardiovascular disease or presence of clinically relevant CNS pathology;
9. Pregnant or nursing women;
10. Subjects Received an autologous or allogeneic hematopoietic stem cell transplant；
11. Uncontrolled conditions or unwillingness or inability to follow the procedures required in the protocol;
12. Received CAR T-cell or other genetically-modified T-cell therapy previously；
13. Received live vaccination within 6 weeks prior to lymphocyte clearance chemotherapy；
14. 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; 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 Day 1.

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
Complete Response (CR) Rate Per the Lugano Classification as Determined by Study Investigators	Complete Response Rate (CRR): percentage of participants with CR [complete metabolic response (CMR); complete radiological response (CRR)]. CMR: positron emission tomography (PET) 5-point scale (5-PS) scores of 1 (no uptake above background), 2 (uptake ≤ mediastinum), 3 (uptake > mediastinum but ≤ liver) with/without a residual mass); no new lesions; and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow (BM). CRR: target nodes/nodal masses regressed to ≤ 1.5 cm in longest transverse diameter of lesion (LDi); no extralymphatic sites of disease; absent non-measured lesion (NMLs); organ enlargement regress to normal; no new sites; and bone marrow normal by morphology.	up to 2 years after Relmacabtagene Autoleucel infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Per the Lugano Classification as Determined by Study Investigators	ORR: percentage of participants with CR [CMR;CRR] or PR [partial metabolic response (PMR); partial radiologic response (PRR)].CMR: PET 5PS scores of 1 (no uptake above background, 2 (uptake ≤ mediastinum), 3 (uptake > mediastinum but ≤ liver) with/without a residual mass; no new lesions; no evidence of FDG-avid disease in BM. CRR:target nodes/nodal masses regressed to ≤ 1.5 cm in LDi;no extralymphatic sites of disease;absent NMLs;organ enlargement regress to normal;no new sites;bone marrow morphology normal. PMR:scores 4 (uptake moderately > liver),5 (uptake markedly > liver, new lesions) with reduced uptake compared with baseline and residual mass;no new lesions;responding disease at interim/residual disease at end of treatment (EOT).PRR: ≥ 50% decrease in sum of the product of perpendicular diameters (SPD) of up to 6 target measurable nodes and extra-nodal sites;absent/normal, regressed, but no increase of NMLs;spleen regressed by > 50% in length beyond normal;no new sites.	up to 2 years after Relmacabtagene Autoleucel infusion
Duration of Response (DOR) Per the Lugano Classification	DOR is defined only for participants who experience an objective response after Relmacabtagene Autoleucel infusion and is the time from the first objective response to disease progression or death from any cause. Objective response is defined in outcome measure (OM) 2.	up to 2 years after Relmacabtagene Autoleucel infusion
Event-Free Survival (EFS)	First infusion date of Relmacabtagene Autoleucel to data cut off	up to 2 years after Relmacabtagene Autoleucel infusion
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
Overall Survival (OS)	OS is defined as the time from Relmacabtagene Autoleucel infusion to the date of death from any cause.	up to 2 years after Relmacabtagene Autoleucel infusion
Types, frequency, and severity of adverse events and laboratory anomalies	Physiological parameter	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
The change of serum cytokines concentration	The change of serum cytokines(IL-2、IL-4、IL-6、IL-8、IL-10、IL-17A、IFN-γ、TNF-α、IFN-α) concentration after Relmacabtagene Autoleucel infusion	up to 1 year after Relmacabtagene Autoleucel infusion

Collaborators and Investigators

• Sponsor: Peking University Cancer Hospital & Institute
• Collaborators: Shanghai Ming Ju Biotechnology Co., Ltd.
• Investigators: Principal Investigator: Yuqin Song, PhD, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2023
• Primary Completion (Estimated): February 10, 2024
• Study Completion (Estimated): December 10, 2024

Study Registration Dates

• First Submitted: October 12, 2022
• First Submitted That Met QC Criteria: October 19, 2022
• First Posted (Actual): October 21, 2022

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: January 5, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; 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: JWCAR029011

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
• product manufactured in and exported from the U.S.: No