ARTA-based Chemo-free Bridging/Maintenance Therapy in CAR-T Treatment for High-Risk R/R B-NHL Ineligible for HDCT and ASCT

Официальное название

Efficacy and Safety of All-trans Retinoic Acid (ATRA)-Based Chemo-free Bridging/Maintenance Therapy in CAR-T Treatment of High-risk Relapsed/Refractory B-NHL Ineligible for High-dose Chemotherapy （HDCT） and Autologous Stem Cell Transplantation （ASCT）

Обзор

This is a single-center, open-label, prospective study enrolling high-risk (tumor diameter \> 4 cm) relapsed/refractory B-NHL patients ineligible for HDCT and ASCT. The treatment consists of ATRA combined with zanubrutinib ± radiotherapy and CAR-T therapy. Based on the efficacy at day 28 post-CAR-T infusion, patients achieving CR will receive 3 months of ATRA and zanubrutinib, while those with PR will receive 3 months of zanubrutinib plus 2 years of ATRA and a PD-1 inhibitor. Patients with stable disease or progression will discontinue. The primary endpoint is the 3-month CR rate following CAR-T infusion.

Вмешательства

• Препарат All-trans retinoic acid
  10mg，tid，po (After apheresis and continued until post-infusion)
• Препарат zanubrutinib
  160mg，bid，po (prior to apheresis and continued until post-infusion)
• Лучевая терапия radiotherapy
  If the patient's specific lesions are suitable for radiotherapy
• Препарат CAR-T
  CAR-T cell therapy
• Препарат PD-1 inhibitor
  IV 200 mg on D1, Q3W

Первичные конечные точки

• Complete Response (CR) Rate at 3-month [Срок оценки: 3 months post CAR-T infusion]

Вторичные конечные точки (3)

• Progression-Free Survival (PFS) [Срок оценки: 2 years post CAR-T infusion]
• Overall Survival (OS) [Срок оценки: 2 years post CAR-T infusion]
• Adverse Events rate as assessed by CTCAE version 5.0 [Срок оценки: 2 years post CAR-T infusion]

Критерии участия

Критерии включения

• Willingly sign the informed consent form.
• Age ≥ 18 years, any gender.
• Histologically confirmed as B-cell non-Hodgkin lymphoma, including:

• Diffuse large B-cell lymphoma (DLBCL) not otherwise specified (DLBCL-NOS)
• Transformed follicular lymphoma (tFL)
• High-grade B-cell lymphoma (HGBL) with MYC, BCL2, and/or BCL6 rearrangements
• High-grade B-cell lymphoma not otherwise specified (HGBL-NOS)
• Primary mediastinal large B-cell lymphoma (PMBL)
• Follicular lymphoma grade 3b (FL3b)
• Patients must have experienced at least one line of treatment for relapsed or refractory disease, meeting the following definitions:

• Refractory: At least partial response (PR) after the last chemotherapy or relapse within 12 months after autologous transplantation.
• Relapsed: Complete response (CR) after the last chemotherapy, followed by relapse before enrollment, or relapse or progression 12 months or longer after autologous transplantation.
• Maximum tumor diameter (long axis) > 4 cm.
• Evaluator determines that the patient does not meet HDCT/ASCT criteria and meets at least one of the following:

• Age ≥ 60 years
• ECOG score = 2
• FEV1% or DLCO% ≤ 60%
• LVEF < 50%
• Creatinine clearance < 60 mL/min
• ALT or AST > 2× upper limit of normal (ULN)
• Patient unwilling to receive high-dose chemotherapy and autologous stem cell transplantation.
• Measurable target lesions: lymph nodes ≥ 15 mm in longest diameter, or extranodal lesions > 10 mm.
• Expected survival ≥ 12 weeks.
• Laboratory tests must meet the following requirements at screening:

• Lymphocyte count ≥ 0.1 × 10\^9/L
• Hemoglobin ≥ 80 g/L
• Platelets ≥ 50 × 10\^9/L
• ALT/AST ≤ 5 × ULN and total bilirubin < 2 × ULN
• Creatinine clearance ≥ 30 mL/min
• Lung function: ≤ CTCAE grade 1 dyspnea, and oxygen saturation (SpO2) ≥ 92% in room air.
• LVEF ≥ 40%
• Patients with primary central nervous system lymphoma are allowed (secondary CNS lymphoma is not allowed).
• Sufficient venous access for apheresis, and no other contraindications for blood cell separation; female participants of childbearing potential must have a negative pregnancy test at screening.

Критерии исключения

• History of allergy to any component of the cellular product or study treatment.
• History of allogeneic hematopoietic stem cell transplantation.
• History of organ transplantation.
• Patients with active viral hepatitis requiring treatment, including:

• Chronic HBV carriers with HBV DNA ≥ 500 IU/mL.
• Positive HCV RNA in patients with positive HCV antibodies.
• Positive HIV antibodies (HIV-Ab).
• Positive Treponema pallidum antibodies (TP-Ab).
• Elevated CMV DNA or EBV DNA above normal limits.
• Clinical significance of CNS diseases
• Presence of active primary central nervous system lymphoma.
• Prior treatment with other genetically modified T-cell therapies or CAR-T therapies.
• Severe genetic diseases or autoimmune diseases (e.g., systemic lupus erythematosus).
• Thromboembolic events (e.g., myocardial infarction, pulmonary embolism, deep vein thrombosis) within 6 months prior to screening.
• History of malignancies other than the indication for this trial within the last 5 years, except for in situ cancers (e.g., cervical, bladder, breast) or non-melanoma skin cancer.
• Active infections requiring systemic treatment or uncontrolled infections.
• Received lenalidomide, calcineurin inhibitors, chemotherapy (e.g., methotrexate, cyclophosphamide, ifosfamide, nitrogen mustard, or melphalan), mycophenolate, thalidomide, immunosuppressive antibodies (e.g., anti-TNF, anti-IL6, or anti-IL6R), radiation therapy, or any drug that binds FKBP12 (e.g., rapamycin, tacrolimus, everolimus) within 4 weeks prior to PBMC collection.
• Pregnant or breastfeeding women, or men or women of childbearing potential unwilling to use contraception during the trial and for 2 years after RJ CAR-T 002 cell infusion.
• Participation in other drug clinical trials (e.g., new drug trials, registrational studies, investigator-initiated trials) within 4 weeks prior to PBMC collection.
• Researcher's judgment that the patient is unsuitable for the trial (e.g., poor compliance, drug abuse).
• Vaccination with live or attenuated vaccines within 3 months prior to PBMC collection, or expected vaccination during the trial.

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

• Department of Hematology, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao — Шанхай

Идентификаторы

NCT: NCT06646666 · CAR-T 002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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