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

NCT06646666 | Not Yet Recruiting Phase 2

• 1 other identifier: CAR-T 002
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

B-cell Non Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR) Rate at 3-month

  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.

  3 months post CAR-T infusion

Secondary Outcomes (3)

• 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

Study Arms (1)

ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-T

EXPERIMENTAL

Drug: All-trans retinoic acid; Drug: zanubrutinib; Radiation: radiotherapy; Drug: CAR-T; Drug: PD-1 inhibitor

Interventions

All-trans retinoic acid DRUG

10mg，tid，po (After apheresis and continued until post-infusion)

ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-T

zanubrutinib DRUG

160mg，bid，po (prior to apheresis and continued until post-infusion)

ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-T

radiotherapy RADIATION

If the patient's specific lesions are suitable for radiotherapy

ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-T

CAR-T DRUG

CAR-T cell therapy

ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-T

PD-1 inhibitor DRUG

IV 200 mg on D1, Q3W

ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-T

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

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

Shanghai, China

Location

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

Tretinoin; zanubrutinib; Radiotherapy; Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors; Therapeutics; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Weili Zhao

CONTACT

+862164370045; zwl_trial@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 15, 2024
• First Posted: October 17, 2024
• Study Start: December 1, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: November 1, 2024

Record last verified: 2024-10

Locations

CN (1)