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NCT06646666 | NOT YET RECRUITING | B-cell Non Hodgkin Lymphoma

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

Ruijin Hospital

Information provided by (Responsible Party):

Zhao Weili

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 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.

Condition or disease

B-cell Non Hodgkin Lymphoma

Intervention/treatment

All-trans retinoic acid

zanubrutinib

radiotherapy

CAR-T

PD-1 inhibitor

Phase

PHASE2

Study Type : INTERVENTIONAL
Estimated Enrollment : 35 participants
Masking : NONE
Primary Purpose : TREATMENT
Official Title : 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）
Actual Study Start Date : 2024-12-01
Estimated Primary Completion Date : 2027-06-01
Estimated Study Completion Date : 2027-12-01

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
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.
ARTA-based Chemo-free Bridging/Maintenance Therapy in CAR-T Treatment for High-Risk R/R B-NHL Ineligible for HDCT and ASCT

Location Details

NCT06646666

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How to Participate

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Locations

Not yet recruiting

China,

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

Shanghai, China,