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

Primary Purpose

B-cell Lymphoma

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Relmacabtagene Autoleucel

Fludarabine

Cyclophosphamide

About this trial

This is an interventional treatment trial for B-cell Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

≥ 18 years old;
Sign on the informed consent;
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)；
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
Expected survival greater than 12 weeks；
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；
Adequate vascular access for leukapheresis procedure;
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:

Lymphoma involving the central nervous system (CNS)；
History of another primary malignancy that has not been in remission for at least 2 years;
History of Richter's transformation of chronic lymphocytic leukemia or primary mediastinal B-cell lymphoma；
Subjects has HBV, HCV, HIV or syphilis infection at the time of screening;
Deep venous thrombosis (DVT)/Pulmonary embolism (PE), or DVT/PE requires anti-coagulation within 3 months prior to signing the ICF;
Subjects with uncontrolled systemic fungal, bacterial, viral or other infection;
Presence of acute or chronic graft-versus-host disease (GVHD);
History of any serious cardiovascular disease or presence of clinically relevant CNS pathology;
Pregnant or nursing women;
Subjects Received an autologous or allogeneic hematopoietic stem cell transplant；
Uncontrolled conditions or unwillingness or inability to follow the procedures required in the protocol;
Received CAR T-cell or other genetically-modified T-cell therapy previously；
Received live vaccination within 6 weeks prior to lymphocyte clearance chemotherapy；
History of severe hypersensitivity reactions to any of the drug ingredients used in this study product.

Sites / Locations

Beijing Cancer HospitalRecruiting
Peking University International HospitalRecruiting
Henan Cancer Hospital
Tianjin Medical University Cancer Institute and Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Relmacabtagene Autoleucel

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

Event-Free Survival (EFS)

First infusion date of Relmacabtagene Autoleucel to data cut off

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.

Overall Survival (OS)

OS is defined as the time from Relmacabtagene Autoleucel infusion to the date of death from any cause.

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

Physiological parameter

Pharmacokinetic (PK)- Cmax of Relmacabtagene Autoleucel

Maximum observed concentration of Relmacabtagene Autoleucel in peripheral blood

Pharmacokinetic (PK)- Tmax of Relmacabtagene Autoleucel

Time to maximum concentration of Relmacabtagene Autoleucel in peripheral blood

Pharmacokinetic (PK)- AUC of Relmacabtagene Autoleucel

Area under the concentration vs time curve of Relmacabtagene Autoleucel

The concentration of Car-T cell

The concentration of Car-T cell in peripheral blood

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

Full Information

NCT ID

NCT05590221

First Posted

October 12, 2022

Last Updated

October 15, 2023

Sponsor

Peking University Cancer Hospital & Institute

Collaborators

Shanghai Ming Ju Biotechnology Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT05590221

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Recruiting

Study Start Date

January 3, 2023 (Actual)

Primary Completion Date

February 10, 2024 (Anticipated)

Study Completion Date

December 10, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Peking University Cancer Hospital & Institute

Collaborators

Shanghai Ming Ju Biotechnology Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

B-cell Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Relmacabtagene Autoleucel

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Relmacabtagene Autoleucel

Other Intervention Name(s)

JWCAR029

Intervention Description

A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells

Intervention Type

Drug

Intervention Name(s)

Fludarabine

Intervention Description

Administered according to package insert

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Intervention Description

Administered according to package insert

Primary Outcome Measure Information:

Title

Complete Response (CR) Rate Per the Lugano Classification as Determined by Study Investigators

Description

Time Frame