NCT06646666尚未招募2 期
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）
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Complete Response (CR) Rate at 3-month
研究概览
简要总结
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.
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
- •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.
排除标准
- •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.
研究组 & 干预措施
ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-T
Experimental
干预措施: All-trans retinoic acid (Drug)
ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-T
Experimental
干预措施: zanubrutinib (Drug)
ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-T
Experimental
干预措施: radiotherapy (Radiation)
ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-T
Experimental
干预措施: CAR-T (Drug)
ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-T
Experimental
干预措施: PD-1 inhibitor (Drug)
结局指标
主要结局
Complete Response (CR) Rate at 3-month
时间窗: 3 months post CAR-T infusion
Complete response rate at 3-month is defined as the incidence of subjects achieving complete remission (CR) within 3 months after CAR-T infusion according to the Lugano Classification (Cheson et al, 2014), as determined by study investigators.
次要结局
- Progression-Free Survival (PFS)(2 years post CAR-T infusion)
- Overall Survival (OS)(2 years post CAR-T infusion)
- Adverse Events rate as assessed by CTCAE version 5.0(2 years post CAR-T infusion)
研究者
研究点 (1)
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