NCT07814001尚未招募2 期
A Phase II Trial Evaluating Fixed Dose and Faster Ramp-up of Epcoritamab With Lenalidomide for 3L Relapse/Refractory Large B-cell Lymphoma After CAR T-cells Therapy in 2nd Line
The Lymphoma Academic Research Organisation15 个研究点 分布在 1 个国家目标入组 55 人开始时间: 2026年12月1日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 55
- 试验地点
- 15
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
The goal of this Phase 2, open-label, multicenter clinical trial is to assess the efficacy and safety of accelerated ramp-up and fixed-dose subcutaneous epcoritamab combined with lenalidomide in adults with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) following progression after second-line CAR T-cell therapy.
The main question it aims to answer is :
- What is the overall response rate (ORR) after Cycle 2, or at premature treatment discontinuation (PTD), according to the 2014 Lugano Response Criteria?
Participants will:
- Receive subcutaneous epcoritamab administered according to an accelerated ramp-up schedule followed by fixed dosing, in combination with lenalidomide.
- Undergo clinical evaluations, laboratory assessments, and PET-CT imaging to determine disease status based on the 2014 Lugano Response Criteria.
- Continue study therapy for up to 48 weeks.
- Enter a follow-up period of at least 24 months after the last dose to monitor long-term outcomes and safety.
Approximately 55 adults will be enrolled across multiple centers in France. Eligible individuals must have R/R LBCL, including diffuse large B-cell lymphoma and other eligible LBCL subtypes, with progressive metabolic disease documented by PET-CT at least 1 month after second-line CAR T-cell therapy. The overall study duration is expected to be approximately 5 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant (or their legally acceptable representative / trusted person) who understand and voluntarily signs and dates an informed consent form prior to any study-specific assessments/procedures being conducted
- •Aged ≥ 18 years at the time of signing the informed consent form (ICF) with no upper age limit
- •Diagnosis at relapse/progression post CAR T-cells of LBCL (de novo or histologically transformed from follicular lymphoma) with histologically confirmed CD20+ disease, inclusive of the following according to WHO 2022 classification and documented in pathology report:
- •Diffuse large B-cell lymphoma (DLBCL), NOS
- •Large B-cell lymphoma (LBCL)
- •T-cell/histiocyte-rich large B-cell lymphoma
- •Transformed follicular lymphoma
- •DLBCL/High-grade B cell lymphoma with MYC and BCL-2 translocations per WHO
- •High-grade B-cell lymphoma, NOS
- •Follicular lymphoma Grade 3B
- •Note: The following, non-exhaustive list of histologies excluded from enrollment: patients with CLL, Richter's, indolent non-Hodgkin lymphoma, transformed WM, transformed MZL and Burkitt lymphoma
- •Participant must have no prior treatment with epcoritamab or any other bispecific antibody targeting CD3 and CD20
- •Relapsing or refractory after two systemic lines of treatment including CAR T-cells therapy (Note: bridging therapy is not considered as a line of treatment)
- •R/R status will be determined by a PET scan performed approximately 1 month after CAR T cells infusion or on subsequent PET scans
- •Note: Participant who received a combination of CAR T-cells therapy and immunomodulatory drugs (IMids) as second line are not eligible
- •ECOG performance status 0 to 2
- •Presence of disease specific criteria allowing response evaluation:
- •Bi-dimensionally measurable disease defined by at least one lymph node > 15 mm or extranodal lesion > 10mm
- •At least one hypermetabolic lesion demonstrated by 18FDG PET-CT (PET0)
- •Adequate hematopoietic function at screening as follows (unless cytopenia is clearly due to bone marrow involvement, or hypersplenism):
- •Hemoglobin level > 8g/dL without RBC transfusion performed within 7 days before epcoritamab infusion
- •ANC ≥ 1 G/L (except if related to lymphoma involvement, ANC must be > 0.5 G/L)
- •Platelets ≥ 50 G/L without platelet transfusion performed within 7 days before epcoritamab (except if related to lymphoma, hypersplenism, platelets must be > 30 G/L)
- •Adequate renal function (calculated MDRD or Cockcroft-Gault): Creatinine Clearance ≥ 40 ml/min
- •Adequate liver function:
- •Total bilirubin ≤ 1.5 x ULN
- •Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 3 x ULN Note: Patients with documented history of Gilbert's Syndrome and in whom total bilirubin elevations are
- •accompanied by elevated indirect bilirubin are eligible
- •No persistent CAR-T neurotoxicity symptoms (regardless of grade)
- •Other adverse events from prior anti-cancer therapy must have resolved to Grade ≤ 1 (excepted the events previously described in criteria 8 to 11)
- •Negative HIV test at screening, with the following exception: Individuals with a positive HIV test at screening are eligible provided they are stable on antiretroviral therapy for at least 4 weeks, have a CD4 count ≥ 200/uL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months.
- •Participant must not have documented refractoriness to IMids and must be suitable for treatment with lenalidomide in the opinion of the investigator.
- •Note: Refractoriness to IMids is defined as:
- •Best response to prior IMids regimen of SD or PD, OR
- •Progressive disease within 6 months of completion of prior IMids regimen
- •Participant must not have had lenalidomide exposure within 12 months prior to screening.
- •Participant must be willing to take aspirin prophylaxis or prophylactic anticoagulation for thromboembolic event (or per local guidelines for lenalidomide administration).
- •Participant must be able to swallow capsules and must not have any disease significantly affecting gastrointestinal function (e.g., resection of the stomach or small bowel, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction).
- •Women of childbearing potential (WOCBP):
- •should have a negative result for pregnancy test (minimum sensitivity of 25mIU/mL, urine or serum) at screening
- •should agree to use at least one efficient method of birth control from 4 weeks prior to study treatment initiation, during study treatment administration and until 4 weeks after the last dose of lenalidomide and until
- •Men of reproductive potential should agree to use an acceptable method of birth control (condom) and must agree not to donate sperm during treatment and for 7 days after the last dose of lenalidomide and until 12 months after the last dose of epcoritamab
排除标准
- •Previously known CD20 negative status, excepted if a new biopsy or cytometry analysis proving a CD20 positive status is available before enrollment
- •Prior solid organ transplantation
- •Prior allogeneic SCT
- •Autologous SCT within 100 days prior to epcoritamab infusion
- •Known or current central nervous system or meningeal involvement by lymphoma
- •Current or past history of Progressive Multifocal Leukoencephalopathy (PML)
- •Current or past history of aphasia, delirium, dementia, cerebellar disease, cognitive disorder, epilepsy under treatment, CNS vasculitis, neurodegenerative disease or dysarthria
- •History of cerebrovascular ischemia / hemorrhage with sequelae
- •Any serious psychiatric illness that would prevent the participant from signing the informed consent form
- •Patients with known active infection, or reactivation of a latent infection, whether bacterial, viral (including, but not limited to symptomatic SARS CoV-2 infection), fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics (for IV antibiotics this pertains to completion of last course of antibiotic treatment) within 1 week prior epcoritamab first injection Note: positive PCR EBV related to lymphoma could be enrolled
- •Known positive HTLV1 serology
- •Active Hepatitis C Virus (HCV) infection (RNA PCR-positive). Participants who received treatment for HCV infection that was intended to eradicate the virus may participate if hepatitis C RNA levels are undetectable,
- •Active Hepatitis B Virus (HBV) infection (DNA PCR-positive).
- •LVEF < 45% as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan
- •Any serious active disease or co-morbid medical condition (such as New York Heart Association Class III or IV cardiac disease, severe arrhythmia, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease (including uncontrolled obstructive pulmonary disease and history of bronchospasm or other according to investigator's decision)
- •Uncontrolled cirrhosis
- •Major surgery or significant traumatic injury < 28 days prior to the epcoritamab infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment
- •Received systemic immunosuppressive medications (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) with the exception ofcorticosteroid treatment < 25 mg/day prednisone or equivalent within 2 weeks prior to epcoritamab first infusion. Inhaled and topical steroids are permitted.
- •Active malignancy other than the one treated in this Study.
- •Prior history of malignancies unless the participant has been free of the disease (in CR) for ≥ 2 years. However, participants with the following history/concurrent conditions are allowed:
- •Non-invasive basal cell or epidermoid carcinoma
- •In situ carcinoma of the cervix
- •In situ carcinoma of the breast
- •Incidental histologic finding of prostate cancer (T1a or T1b) using the tumor, nodes, metastasis [TNM] clinical staging system Note: Woman with adjuvant endocrine therapy (i.e., hormonotherapy) after breast cancer treatment can be enrolled if hormonotherapy was started for ≥ 2 years
- •Known or suspected hypersensitivity to the active substance or to any of the excipients.
- •Prior treatment within 4 weeks or five half-lives of the drug, whichever is shorter, before epcoritamab infusion with: - standard radiotherapy
- •any chemotherapeutic agent or treatment with any other investigational anti-cancer agents (defined as treatment for which there is currently no regulatory authority approved indication)
- •systemic immunotherapeutic agents, including, but not limited to, radio-immunoconjugates, antibody-drug conjugates, immune/cytokines and monoclonal antibodies (e.g., anti-CTLA4, anti-PD1 and anti-PDL1)
- •Pregnant, planning to become pregnant or lactating or breastfeeding woman of childbearing potential
- •Pregnant, planning to become pregnant or lactating or breastfeeding woman of childbearing potential
- •Any significant medical conditions, or laboratory abnormality or psychiatric illness likely to interfere with participation in this clinical study (according to the investigator's decision)
- •Participant deprived of his/her liberty by a judicial or administrative decision
- •Participant hospitalized without consent
- •Adult participant under legal protection
研究组 & 干预措施
Epcoritamab plus Lenalidomide
Experimental
All enrolled participants will be included in a single cohort. No comparator group will be included.
干预措施: Epcoritamab (Drug)
Epcoritamab plus Lenalidomide
Experimental
All enrolled participants will be included in a single cohort. No comparator group will be included.
干预措施: Lenalidomide (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: At the end of Cycle 2 (each cycle is 28 days) or until premature treatment discontinuation (PTD) from any cause, whichever occurs first, assessed up to 56 days
Overall response rate (ORR), defined as the proportion of participants achieving a complete response (CR) or partial response (PR) according to the 2014 Lugano Response Criteria following treatment with accelerated ramp-up dosing and fixed-dose epcoritamab in combination with lenalidomide.
次要结局
- Best Overall Response Rate (Best ORR)(From Cycle 1 through the end of Cycle 8 (each cycle is 28 days) or until premature treatment discontinuation (PTD) from any cause, whichever occurs first, assessed up to 224 days.)
- Complete Metabolic Response (CMR) Rate(At Cycles 1, 2, 5, 8, and 12 (each cycle is 28 days), assessed up to 336 days.)
- Duration of Response (DoR)(From the date of first documented partial or complete response until the date of first documented disease progression, relapse, or death from any cause, whichever occurs first, assessed up to 54 months ( end of follow-up).)
- Incidence of Cytopenias(From Cycle 1 until Cycle 12 ( each cycle is 28 days) or until the date of the permanent treatment discontinuation (PTD) from any cause, whichever occurs first. Assessed up to 336 days)
- Progression-Free Survival (PFS)(From date of Cycle 1 (each cycle is 28 days)until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 54 months)
- Overall Survival (OS)(From Cycle 1 ( 28 days) until date of death, or until end of follow-up (up to 54 months))
- Incidence of Tumor Lysis Syndrome (TLS)(From Cycle 1 until Cycle 12 ( each cycle is 28 days) or until the date of the permanent treatment discontinuation (PTD) or date of death from any cause, whichever occurs first. Assessed up to 336 days.)
- Incidence of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)(From Cycle 1 until Cycle 12 ( each cycle is 28 days) or until the date of the permanent treatment discontinuation (PTD) from any cause, whichever occurs first. Assessed up to 336 days)
- Incidence of Cytokine Release Syndrome (CRS)(From Cycle 1 until Cycle 12 ( each cycle is 28 days) or until the date of the permanent treatment discontinuation (PTD) from any cause, whichever occurs first. Assessed up to 336 days)
- Incidence of Infections(From Cycle 1 until Cycle 12 ( each cycle is 28 days) or until the date of the permanent treatment discontinuation (PTD) from any cause, whichever occurs first. Assessed up to 336 days)
研究者
研究点 (15)
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