NCT07316920尚未招募1 期
An Exploratory Clinical Study of the Safety and Efficacy of RN1701 Injection in the Treatment of Relapsed/Refractory B-Cell Lymphomas
YANRU WANG1 个研究点 分布在 1 个国家目标入组 19 人开始时间: 2025年12月22日最近更新:
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Toxicity and adverse-event grading after RN1701 treatment
研究概览
简要总结
This single-arm, open-label pilot study will assess the safety and efficacy of RN1701, a bispecific CD19/CD20-targeted allogeneic CAR-T-cell product, in patients with relapsed or refractory B-cell lymphoma. Up to 19 participants will be enrolled in a conventional 3 + 3 dose-escalation scheme. The primary objective of the study is to evaluate the safety and feasibility of RN1701 for the treatment of relapsed/refractory B-cell lymphoma. The secondary objective is to evaluate the efficacy of RN1701 for the treatment of relapsed/refractory B-cell lymphoma. The exploratory objective is to evaluate the expansion, persistence, and ability of RN1701 to deplete CD19- and/or CD20-positive cells in patients with relapsed/refractory B-cell lymphoma.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary participation; full understanding of the study and provision of written informed consent obtained before any study-related procedure not part of standard care; willingness to comply with follow-up.
- •Age 18-75 years; either sex.
- •ECOG performance status 0-
- •Histologically confirmed large B-cell lymphoma, follicular lymphoma, mantle-cell lymphoma, or indolent lymphoma transformed to DLBCL; CD19 and/or CD20 positive.
- •At least one measurable lesion per Lugano criteria: nodal lesion longest diameter >1.5 cm, extranodal lesion >1.0 cm.
- •Prior treatment response must meet one of the following:
- •Large B-cell lymphoma, grade 3B follicular lymphoma, transformed indolent lymphoma: i. Primary refractory and ineligible/unable to receive autologous CAR-T: best response PD after ≥2 cycles of first-line therapy, or SD after ≥4 cycles.
- •ii. Relapse ≤12 months after achieving CR with first-line chemo-immunotherapy. iii. Relapse/progression ≤12 months after autologous HSCT. iv. Refractory to, relapsed after, or progressed on ≥2 prior lines (including autologous CAR-T): best response PD or SD after ≥2 cycles of the most recent regimen.
- •v. Transformed indolent lymphoma: prior chemotherapy for iNHL and ≥1 systemic regimen after transformation, fulfilling the above refractory/relapse criteria.
- •Grade 1, 2, or 3A follicular lymphoma: i. Primary refractory and ineligible/unable to receive autologous CAR-T: best response PD after ≥2 cycles of first-line therapy.
- •ii. Refractory to, relapsed after, or progressed on ≥2 prior lines (including autologous CAR-T): best response PD or SD after ≥2 cycles of the most recent regimen.
- •Mantle-cell lymphoma: i. Primary refractory and ineligible/unable to receive autologous CAR-T: best response PD after ≥2 cycles of first-line therapy, or SD after ≥4 cycles.
- •ii. Refractory to, relapsed after, or progressed on ≥2 prior lines (including autologous CAR-T): best response PD or SD after ≥2 cycles of the most recent regimen.
- •Estimated life expectancy ≥3 months.
- •Screening laboratory values (may be repeated once):
- •Hemoglobin ≥8.0 g/dL (no transfusion within 7 days).
- •Platelets ≥50×10⁹/L (no transfusion within 7 days).
- •ANC ≥1.0×10⁹/L (growth-factor support allowed if none within 7 days of test).
- •AST/ALT ≤3×ULN (≤5×ULN if liver involvement).
- •Serum creatinine ≤1.5×ULN or CrCl ≥60 mL/min (Cockcroft-Gault).
- •Total bilirubin ≤2×ULN (≤3×ULN if liver involvement); except congenital bilirubin disorders (e.g., Gilbert's syndrome: direct bilirubin ≤1.5×ULN).
- •INR, PT, APTT <1.5×ULN.
- •Toxicities from prior anti-cancer therapy (except alopecia, nausea, and the above lab values) must have stabilized at baseline or resolved to ≤Grade
- •WOCBP must have a negative high-sensitivity serum β-hCG pregnancy test at screening and again before the first dose of cyclophosphamide/fludarabine.
- •Subjects of reproductive potential must use effective contraception for ≥12 months after completing study therapy.
排除标准
- •Subjects with any of the following conditions are ineligible for this trial:
- •Any malignancy other than B-cell non-Hodgkin lymphoma ever diagnosed or treated, except:
- •Malignancy that received curative therapy and has shown no evidence of active disease for ≥2 years before enrolment; or
- •Adequately treated non-melanoma skin cancer with no current evidence of disease.
- •Prior anti-cancer therapy within the stated windows (before lymphodepletion):
- •CNS prophylaxis (e.g., intrathecal methotrexate and/or cytarabine) within 7 days;
- •Cytotoxic chemotherapy or radiotherapy within 14 days;
- •Small-molecule targeted or epigenetic therapy within 14 days or 5 half-lives, whichever is longer;
- •Monoclonal antibody, bispecific antibody, or antibody-drug conjugate within 21 days or 5 half-lives, whichever is shorter;
- •Investigational drug or invasive investigational device within 28 days (if the therapy is also investigational, the 28-day wash-out applies);
- •Autologous haematopoietic stem-cell transplant or CD19-directed autologous CAR-T therapy within 100 days.
- •Any autologous cellular or gene therapy other than CD19-directed autologous CAR-T.
- •Any allogeneic cellular (including CAR-T) or gene therapy.
- •Prior allogeneic haematopoietic stem-cell transplantation.
- •Positive donor-specific antibody (DSA).
- •At least one of the following high-risk features:
- •Sum of the product of perpendicular diameters (SPD) of all measurable lesions ≥100 cm²;
- •Bulky disease: single mass ≥7.5 cm; mediastinal mass with maximum diameter >1/3 of thoracic diameter;
- •Obstructive/compressive emergency (e.g., bowel obstruction, vascular compression) requiring urgent intervention at screening.
- •Active CNS involvement (symptomatic or positive CSF/imaging); subjects with prior CNS disease now in remission (asymptomatic with negative CSF and imaging) are eligible.
- •Significant bleeding diathesis: gastrointestinal bleeding, haemorrhagic cystitis, coagulopathy, hypersplenism (splenomegaly on exam/US, cytopenias, hyperplastic marrow) or ongoing anticoagulation.
- •Chronic concomitant systemic corticosteroids or other immunosuppressants, except: topical, ocular, intra-articular, nasal or inhaled corticosteroids; short-course steroids for prophylaxis (e.g., contrast allergy).
- •Severe underlying medical conditions:
- •Active serious viral, bacterial or uncontrolled systemic fungal infection;
- •Active systemic autoimmune disease requiring therapy.
- •Significant cardiac disease:
- •NYHA class III or IV congestive heart failure;
- •Myocardial infarction or CABG within 6 months before enrolment;
- •Clinically relevant ventricular arrhythmia or unexplained syncope not vasovagal or dehydration-related;
- •Severe non-ischaemic cardiomyopathy;
- •Left ventricular ejection fraction (LVEF) <45% by echo or MUGA within 4 weeks before lymphodepletion.
- •Resting oxygen saturation <92%.
- •Clinically relevant prior or current CNS disorder: epilepsy, seizure-like episodes, paralysis, aphasia, stroke, severe head trauma, dementia, Parkinson's disease, cerebellar disorder, organic brain syndrome or major psychiatric illness.
- •Live-attenuated vaccine within 4 weeks before screening.
- •Major surgery within 2 weeks before screening or planned within 2 weeks after study treatment (local anaesthesia allowed).
- •Positive screen for HBsAg, HBeAg, HBV DNA, HCV antibody, HCV RNA, or HIV antibody.
- •Life-threatening allergy, hypersensitivity or intolerance to study-drug excipients including, but not limited to, DMSO.
- •Lactating women.
- •Any condition that, in the investigator's opinion, renders the subject unsuitable for the study.
研究组 & 干预措施
Relapsed/refractory B-cell lymphoma
Experimental
Relapsed/refractory B-cell lymphoma patients to be treated with RN1701 cells.
干预措施: RN1701 injection (Biological)
结局指标
主要结局
Toxicity and adverse-event grading after RN1701 treatment
时间窗: up to 12 months after infusion
all toxicities and AEs will be assessed according to the National Cancer Institute CTCAE v5.0
CRS grading after RN1701 treatment
时间窗: up to 12 months after infusion
Cytokine Release Syndrome (CRS) will be graded using the Lee DW et al. CRS grading scale. Grade 1: Fever, mild symptoms, manageable with supportive care Grade 2: Moderate symptoms (eg, hypotension, hypoxia), requires intervention (eg, intravenous fluids, antipyretics) Grade 3: Severe symptoms (eg, multiorgan involvement), requires corticosteroids and tocilizumab Grade 4: Life-threatening, requires intensive care unit (ICU) care and urgent interventions
次要结局
- Overall response rate (ORR = CR + PR) of patients receive RN1701 treatment(1, 3, 6, and 12 months after infusion)
- Disease control rate (DCR = CR + PR + SD) of patients receive RN1701 treatment(1, 3, 6, and 12 months after infusion)
- Assessment includes contrast-enhanced CT of head/neck, chest, abdomen, and pelvis, plus whole-body PET-CT(1, 3, 6, and 12 months after infusion)
- CAR copies and cell count of CAR-T in blood after RN1701 treatment(Days 0, 1, 3, 5, 7, 9, 11, 14, 21, 28 and month 2, 3, 6, 9, 12 after infusion)
研究者
YANRU WANG
Clinical Professor
Affiliated Hospital of Jiangsu University
研究点 (1)
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