Clinical Study of the Safety and Efficacy of the R/R B-NHL Regimen With BTK Inhibitor+Anti-CD19 CAR-T Cells

Prospective, Multicenter, Open, One-arm Clinical Study of the Safety and Efficacy of the R/R B-NHL Regimen With BTK Inhibitor+Anti-CD19 CAR-T Cells

To evaluate the ORR (CR+PR) of R/R B-NHL subjects treated with BTKi+Anti-CD19 CAR T cells.

Study Overview

• Status: Recruiting
• Conditions: B-cell Non Hodgkin Lymphoma
• Intervention / Treatment: Biological: regimen with BTK inhibitor +Anti-CD19 CAR T cells

Detailed Description

The most successful application of CAR-T cell technology in clinical practice is for the treatment of hematologic malignancies, which may be related to the strong specificity of tumor-associated antigen and the weak immunosuppressive effect of tumor microenvironment. CD19 is specifically expressed in B cells and is expressed in all stages of B-cell development and differentiation and in most B-cell tumors, but not in hematopoietic stem cells and other cells. CD19 is a promising target for B-cell tumors and is currently a hot spot in CAR studies.

Antigen-dependent BCR signaling is involved in several downstream pathways, including NF-kB pathway and PI3K/AKT/mTOR pathway, which can promote B cell survival. BTK inhibitors can jointly inhibit the survival of tumor cells by promoting apoptosis and inhibiting the proliferation of tumor cells, reducing the adhesion of tumor cells, and inhibiting chemokines to prevent the migration of B cells.

In this study, BTKi (Ibrutinib) combined with Anti-CD19 CAR-T cells were proposed to treat RR B-NHL, with the main purpose of observing the efficacy and safety of this regimen in patients with relapsed and refractory B-NHL.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221002
      • Recruiting
      • The Affiliated Hospital of Xuzhou Medical University
      • Contact: Wei Sang, M.D., Ph.D.; Phone Number: 13645207648; Email: xyfylbl515@xzhmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients or their legal guardians voluntarily participate and sign the informed consent;
2. Male or female patients aged 18-70 years old;
3. CD19+ B-NHL was confirmed by pathology and histology, and the patient had no effective treatment options at present, such as chemotherapy or hematopoietic stem cell transplantation after recurrence; Or patients voluntarily chose BTKi+Anti-CD19 CAR T as salvage therapy;
4. Subjects showed residual lesions after major treatment and were not suitable for HSCT; Relapse occurs after CR and is not suitable for HSCT; Patients with high risk factors; Relapse or no remission after hematopoietic stem cell transplantation or cellular immunotherapy;
5. Have measurable or evaluable lesions;
6. The patient's main tissues and organs function well;
7. The patient's peripheral shallow venous blood flow is smooth, which can meet the needs of intravenous drip.
8. Patients with ECOG score ≤2, estimated survival time ≥3 months, age ≥ 12 years, ≤ 75 years.

Exclusion Criteria:

1. Women who are pregnant (urine/blood pregnancy test is positive) or breastfeeding;
2. Men or women who have planned to get pregnant within the last 1 year;
3. The patients were not guaranteed to take effective contraceptive measures (condom or contraceptive, etc.) within 1 year after enrollment;
4. Patients had uncontrollable infectious diseases within 4 weeks prior to enrollment;
5. Active hepatitis B/C virus;
6. HIV-infected patients;
7. Suffering from a serious autoimmune disease or immunodeficiency disease;
8. The patient is allergic to antibodies, cytokines and other macromolecular biological drugs;
9. The patient had participated in other clinical trials within 6 weeks prior to enrollment;
10. Systemic use of hormones within 4 weeks prior to enrollment (except for inhaled hormones);
11. Suffering from mental illness;
12. The patient has substance abuse/addiction;
13. According to the researchers' judgment, the patient had other conditions that were not suitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CAR-T Cell Infusion; After FC regimen (fludarabine (25mg/m2/d) on days -5 to -3 and cyclophosphamide (750mg/m2) on days -5) were pretreated, Anti-CD19 CAR T cells were transfused on day 0. The dose was determined by the investigator according to the subjects' own disease conditions and in vitro preparation. Intravenous drip/push at a constant rate for 30 minutes; Ibrutinib, a BTK inhibitor, was enrolled with a standard dose of 560mg qd.

Biological: regimen with BTK inhibitor +Anti-CD19 CAR T cells; After FC regimen (fludarabine (25mg/m2/d) on days -5 to -3 and cyclophosphamide (750mg/m2) on days -5) were pretreated, Anti-CD19 CAR T cells were transfused on day 0. The dose was determined by the investigator according to the subjects' own disease conditions and in vitro preparation. Intravenous drip/push at a constant rate for 30 minutes; Ibrutinib, a BTK inhibitor, was enrolled with a standard dose of 560mg qd.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate	CR+PR	From 1 month to 1 year.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of complete response	Percentage of complete response	From 1 month to 1 year.
Progression-free survival	The time between treatment and observation of disease progression or death from any cause.	From 1 month to 1 year.
Duration of response	Duration of response	From 1 month to 1 year.

Collaborators and Investigators

• Sponsor: The Affiliated Hospital of Xuzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: February 14, 2023
• First Submitted That Met QC Criteria: February 23, 2023
• First Posted (Actual): February 24, 2023

Study Record Updates

• Last Update Posted (Actual): February 24, 2023
• Last Update Submitted That Met QC Criteria: February 23, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: BTK inhibitor; Anti CD19 CAR-T cells
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell
• Other Study ID Numbers: XYFY2022-KL365-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No