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

NCT05590221 | Unknown Phase 2 DMC

• 1 other identifier: JWCAR029011
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 4

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.

Conditions

B-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Objective Response Rate (ORR) Per the Lugano Classification as Determined by Study Investigators

  up to 2 years after Relmacabtagene Autoleucel infusion

• Duration of Response (DOR) Per the Lugano Classification

  up to 2 years after Relmacabtagene Autoleucel infusion

• Event-Free Survival (EFS)

  up to 2 years after Relmacabtagene Autoleucel infusion

• Progression-Free Survival (PFS)

  up to 2 years after Relmacabtagene Autoleucel infusion

• Overall Survival (OS)

  up to 2 years after Relmacabtagene Autoleucel infusion

Study Arms (1)

Relmacabtagene Autoleucel

EXPERIMENTAL

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.

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

Interventions

Relmacabtagene Autoleucel BIOLOGICAL

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

Also known as: JWCAR029

Relmacabtagene Autoleucel

Fludarabine DRUG

Administered according to package insert

Relmacabtagene Autoleucel

Cyclophosphamide DRUG

Administered according to package insert

Relmacabtagene Autoleucel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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：
• Absolute neutrophil count ≥ 1000/μL；Absolute lymphocyte count ≥ 100/μL； Platelet count ≥ 75,000/μL；Hb ≥ 80g/L；
• 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)；
• 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）；
• Baseline oxygen saturation \> 92% on room air；
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead
• Shanghai Ming Ju Biotechnology Co., Ltd.: collaborator

Study Sites (4)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100010, China

RECRUITING

Peking University International Hospital

Beijing, Beijing Municipality, 100010, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, 450003, China

NOT YET RECRUITING

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, 300060, China

NOT YET RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

relmacabtagene autoleucel; fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Yuqin Song, PhD

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuqin Song, PhD

CONTACT

+86 010-88121122; songyuqin622@163.com

Medical JWCAR029

CONTACT

+86 21 50464201; JWCAR029Medical@jwtherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2022
• First Posted: October 21, 2022
• Study Start: January 3, 2023
• Primary Completion: February 10, 2024
• Study Completion: December 10, 2024
• Last Updated: January 8, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)