A Clinical Study of of RN1701 Injection in the Treatment of Relapsed/Refractory B-Cell Lymphomas

Официальное название

An Exploratory Clinical Study of the Safety and Efficacy of RN1701 Injection in the Treatment of Relapsed/Refractory B-Cell Lymphomas

Обзор

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.

Вмешательства

• Биопрепарат RN1701 injection
  RN1701 injection is a bispecific CD19/CD20-targeted allogeneic CAR-T. A single infusion of CAR-T cells will be administered intravenously

Первичные конечные точки

• Toxicity and adverse-event grading after RN1701 treatment [Срок оценки: up to 12 months after infusion]
• CRS grading after RN1701 treatment [Срок оценки: up to 12 months after infusion]

Вторичные конечные точки (4)

• Overall response rate (ORR = CR + PR) of patients receive RN1701 treatment [Срок оценки: 1, 3, 6, and 12 months after infusion]
• Disease control rate (DCR = CR + PR + SD) of patients receive RN1701 treatment [Срок оценки: 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 [Срок оценки: 1, 3, 6, and 12 months after infusion]
• CAR copies and cell count of CAR-T in blood after RN1701 treatment [Срок оценки: Days 0, 1, 3, 5, 7, 9, 11, 14, 21, 28 and month 2, 3, 6, 9, 12 after infusion]

Критерии участия

Критерии включения

• 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 0-1.
• 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 1.
• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Affiliated Hospital of Jiangsu University — Zhenjiang

Идентификаторы

NCT: NCT07316920 · RN1701JB

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗