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

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

NCT ID: NCT06646666

Condition: B-cell Non Hodgkin Lymphoma

Conditions: Official terms:
Lymphoma, B-Cell
Tretinoin
Zanubrutinib
Immune Checkpoint Inhibitors

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: All-trans retinoic acid
Description: 10mg，tid，po (After apheresis and continued until post-infusion)
Arm group label: ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-T

Intervention type: Drug
Intervention name: zanubrutinib
Description: 160mg，bid，po (prior to apheresis and continued until post-infusion)
Arm group label: ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-T

Intervention type: Radiation
Intervention name: radiotherapy
Description: If the patient's specific lesions are suitable for radiotherapy
Arm group label: ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-T

Intervention type: Drug
Intervention name: CAR-T
Description: CAR-T cell therapy
Arm group label: ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-T

Intervention type: Drug
Intervention name: PD-1 inhibitor
Description: IV 200 mg on D1, Q3W
Arm group label: ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-T

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 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.

Criteria for eligibility:
Criteria:
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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Department of Hematology, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Address:
City: Shanghai
Country: China

Start date: December 1, 2024

Completion date: December 1, 2027

Lead sponsor:
Agency: Ruijin Hospital
Agency class: Other

Source: Ruijin Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06646666