ARTA-based Chemo-free Bridging/Maintenance Therapy in CAR-T Treatment for High-Risk R/R B-NHL Ineligible for HDCT and ASCT
- Conditions
- Interventions
- Registration Number
- NCT06646666
- Lead Sponsor
- Ruijin Hospital
- Brief Summary
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 ATR...
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 35
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Willingly sign the informed consent form.
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Age ≥ 18 years, any gender.
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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)
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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.
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Maximum tumor diameter (long axis) > 4 cm.
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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.
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Measurable target lesions: lymph nodes ≥ 15 mm in longest diameter, or extranodal lesions > 10 mm.
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Expected survival ≥ 12 weeks.
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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%
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Patients with primary central nervous system lymphoma are allowed (secondary CNS lymphoma is not allowed).
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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.
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History of allergy to any component of the cellular product or study treatment.
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History of allogeneic hematopoietic stem cell transplantation.
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History of organ transplantation.
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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.
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Clinical significance of CNS diseases
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Presence of active primary central nervous system lymphoma.
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Prior treatment with other genetically modified T-cell therapies or CAR-T therapies.
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Severe genetic diseases or autoimmune diseases (e.g., systemic lupus erythematosus).
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Thromboembolic events (e.g., myocardial infarction, pulmonary embolism, deep vein thrombosis) within 6 months prior to screening.
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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.
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Active infections requiring systemic treatment or uncontrolled infections.
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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.
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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.
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Participation in other drug clinical trials (e.g., new drug trials, registrational studies, investigator-initiated trials) within 4 weeks prior to PBMC collection.
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Researcher's judgment that the patient is unsuitable for the trial (e.g., poor compliance, drug abuse).
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Vaccination with live or attenuated vaccines within 3 months prior to PBMC collection, or expected vaccination during the trial.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-T All-trans retinoic acid - ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-T zanubrutinib - ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-T radiotherapy - ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-T CAR-T - ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-T PD-1 inhibitor -
- Primary Outcome Measures
Name Time Method Complete Response (CR) Rate at 3-month 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.
- Secondary Outcome Measures
Name Time Method Progression-Free Survival (PFS) 2 years post CAR-T infusion PFS is defined as the time from the CAR-T infusion date to the date of disease progression or death from any cause.
Overall Survival (OS) 2 years post CAR-T infusion OS is defined as the time from CAR-T infusion to the date of death from any cause.
Adverse Events rate as assessed by CTCAE version 5.0 2 years post CAR-T infusion An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associate...
Trial Locations
- Locations (1)
Department of Hematology, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, China