Clinical trial · Interventional
ARTA-based Chemo-free Bridging/Maintenance Therapy in CAR-T Treatment for High-Risk R/R B-NHL Ineligible for HDCT and ASCT
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)
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| B-cell Non Hodgkin Lymphoma | B-Cell Non-Hodgkin Lymphoma | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (5)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| All-trans retinoic acid | Drug | Tretinoin | ALIAS |
| CAR-T | Drug | — | UNRESOLVED |
| PD-1 inhibitor | Drug | — | UNRESOLVED |
| radiotherapy | Radiation | — | UNRESOLVED |
| zanubrutinib | Drug | Zanubrutinib | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-T
- interventionNames
- Drug: All-trans retinoic acid
- Drug: zanubrutinib
- Radiation: radiotherapy
- Drug: CAR-T
- Drug: PD-1 inhibitor
Primary outcomes (1)
- measure
- Complete Response (CR) Rate at 3-month
- timeFrame
- 3 months post CAR-T infusion
- description
- 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 outcomes (3)
- measure
- Progression-Free Survival (PFS)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * 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. Exclusion Criteria: * 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.
References
Publications (0)
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