Clinical trial NCT05590221: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: B-cell Lymphoma
Lead sponsor: Peking University Cancer Hospital & Institute
Sponsor class: OTHER
Collaborators: name: Shanghai Ming Ju Biotechnology Co., Ltd.
First posted: 2022-10-21
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Complete Response (CR) Rate Per the Lugano Classification as Determined by Study Investigators
timeFrame: up to 2 years after Relmacabtagene Autoleucel infusion
Secondary outcomes:
measure: Objective Response Rate (ORR) Per the Lugano Classification as Determined by Study Investigators
timeFrame: up to 2 years after Relmacabtagene Autoleucel infusion
measure: Duration of Response (DOR) Per the Lugano Classification
timeFrame: up to 2 years after Relmacabtagene Autoleucel infusion
measure: Event-Free Survival (EFS)
timeFrame: up to 2 years after Relmacabtagene Autoleucel infusion
measure: Progression-Free Survival (PFS)
timeFrame: up to 2 years after Relmacabtagene Autoleucel infusion
measure: Overall Survival (OS)
timeFrame: up to 2 years after Relmacabtagene Autoleucel infusion
measure: Types, frequency, and severity of adverse events and laboratory anomalies
timeFrame: up to 2 years after Relmacabtagene Autoleucel infusion
measure: Pharmacokinetic (PK)- Cmax of Relmacabtagene Autoleucel
timeFrame: up to 1 year after Relmacabtagene Autoleucel infusion
measure: Pharmacokinetic (PK)- Tmax of Relmacabtagene Autoleucel
timeFrame: up to 1 year after Relmacabtagene Autoleucel infusion
measure: Pharmacokinetic (PK)- AUC of Relmacabtagene Autoleucel
timeFrame: up to 1 year after Relmacabtagene Autoleucel infusion
measure: The concentration of Car-T cell
timeFrame: up to 1 year after Relmacabtagene Autoleucel infusion
measure: The change of serum cytokines concentration
timeFrame: up to 1 year after Relmacabtagene Autoleucel infusion
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University International Hospital
state: Beijing
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Yuqin Song, PhD
role: PRINCIPAL_INVESTIGATOR
References: