Autologous Cells Derived Anti-CD19 CAR-Engineered T Cells With Concurrent BTK Inhibitor for B Cell Lymphoma

NCT05020392 | Unknown Phase 3 FDA Drug

• 1 other identifier: auto-CART-CD19 cells and BTKi
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, open-label and pragmatic clinical trial to evaluate the primary efficacy and safety of anti-CD19 chimeric antigen receptor (CAR)-modified T cells (CART-CD19) with concurrent BTK inhibitor in patients with relapsed or refractory B cell lymphoma

Conditions

Diffuse Large B Cell Lymphoma; Burkitt Lymphoma; Follicular Lymphoma; Chronic Lymphocytic Leukemia; Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-related Adverse Events

  Therapy-related adverse events (AE), including severe adverse events (SAE) and laboratory outliers with clinical significance, will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).

  within 2 years after infusion

Secondary Outcomes (6)

• Overall response rate (ORR) of administering CAR-T-CD19 cells or CAR-T-CD19 cells with oral BTK inhibitor in Relapsed/Refractory B cell lymphoma.

  within 2 years after infusion

• Duration of Response (DOR) of administering CAR- T-CD19 cells or CAR-T-CD19 cells with oral BTK inhibitor in Relapsed/Refractory CD19+ B-cell lymphoma.

  within 2 years after infusion

• Overall survival (OS) of administering CAR- T-CD19 cells or CAR-T-CD19 cells with oral BTK inhibitor in Relapsed/Refractory CD19+ B-cell lymphoma.

  within 2 years after infusion

• PFS will be assessed from CAR-T cell infusion to death or last follow-up

  within 2 years after infusion

• Complete response rate (CR) of administering CAR-T-CD19 cells or CAR-T-CD19 cells with oral BTK inhibitor in Relapsed/Refractory B cell lymphoma.

  within 2 years after infusion

Other Outcomes (1)

• In vivo expansion and survival of CAR-T-CD19 cells

  within 2 years after infusion

Study Arms (2)

Effective of CAR-T-CD19 cells with concurrent BTK inhibitor

EXPERIMENTAL

After enrollment, all subjects will receive oral BTK inhibitor immediately and BTK inhibitor treatment will continue for up to 90 days (or longer for who are benefiting from BTK inhibitor) after CAR-T-CD19 infusion. Eligible patients will undergo leukapheresis to obtain peripheral blood mononuclear cells (PBMCs) for CAR T-cell production. Upon successful generation CAR-T-CD19 product, participants will receive fludarabine-based lymphodepletion chemotherapy, followed by infusion of CAR-T-CD19 cells (2\*10\^6 cells/kg) on day 0 and day 1 respectively.

Drug: BTK inhibitor+ Fludarabine-based chemotherapy + CAR-T-CD19 Cells

Effective of CAR-T-CD19 cells monotherapy

ACTIVE COMPARATOR

Eligible patients will undergo leukapheresis to obtain peripheral blood mononuclear cells (PBMCs) for CAR T-cell production. Upon successful generation CAR-T-CD19 product, participants will receive fludarabine-based lymphodepletion chemotherapy, followed by infusion of CAR-T-CD19 cells (2\*10\^6 cells/kg) on day 0 and day 1 respectively.

Drug: Fludarabine-based chemotherapy + CAR-T-CD19 Cells

Interventions

BTK inhibitor+ Fludarabine-based chemotherapy + CAR-T-CD19 Cells DRUG

BTK inhibitor from enrollment to more than 90 days after CAR-T-CD19 infusion. Fludarabine-based lymphodepletion chemotherapy was followed by CART19 infusion at a dose of 1x10\^6/kg on day 0 and day 1 respectively.

Effective of CAR-T-CD19 cells with concurrent BTK inhibitor

Fludarabine-based chemotherapy + CAR-T-CD19 Cells DRUG

Fludarabine-based lymphodepletion chemotherapy was followed by CART19 infusion at a dose of 1x10\^6/kg on day 0 and day 1 respectively.

Effective of CAR-T-CD19 cells monotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥ 18 years and ≤70 years.
• Expected survival over 6 months.
• Eastern Cooperative Oncology Group score≤ 2.
• Diagnosed pathologically and histologically CD19+B cell lymphoma, including mantle cell lymphoma, chronic lymphocytic leukemia, follicular cell lymphoma, Burkitt lymphoma and diffuse large B cell lymphoma.
• Patients have failed at least 1 line of prior therapy
• Negativity of blood pregnancy test for woman, and participants use effective methods of contraception until last follow-up.
• Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.

You may not qualify if:

• Investigators judge the patients with gastrointestinal lymph node and/or central nervous system involvement who may be at high-risk of receiving CAR-T-CD19 cell treatment.
• Existing or preexisting CNS conditions, such as epileptic seizures, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any CNS related autoimmune diseases.
• Patients with graft-versus-host reaction and need immunosuppressive agents, or patients with autoimmune diseases.
• Participants with other active malignancies (except non-melanoma skin cancer and cervical cancer) within five years.
• History of Richter's syndrome.
• History of any one of the following cardiovascular conditions within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease.
• Patients who are pregnant or breast-feeding.
• Patients with any one of the following terms:
• A. Creatine \>2.5mg/dl (221.0umol/L). B. Alanine aminotransferase/aspartate aminotransferase \>3 times the upper limit of normal (ULN).
• C. Total bilirubin\>2.0 mg/dl (34.2umol/L).
• Major surgery within 4 weeks of randomization.
• Systemic steroids are used within 2 weeks before apheresis (Except for those who are using inhaled steroids recently or currently).
• Patients receive cytotoxic chemotherapy or radiotherapy within 21 days before enrollment (Tyrosine kinase inhibitors or other targeted therapies can be used two weeks before lymphodepleting chemotherapy).
• Prior treatment with any gene therapy product.
• Active hepatitis B, active hepatitis C, or active human immunodeficiency virus (HIV) infection.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead
• Wuhan Si'an Medical Technology Co., Ltd: collaborator

Study Sites (1)

Union Hospital, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

RECRUITING

Related Publications (4)

• Gauthier J, Hirayama AV, Purushe J, Hay KA, Lymp J, Li DH, Yeung CCS, Sheih A, Pender BS, Hawkins RM, Vakil A, Phi TD, Steinmetz RN, Shadman M, Riddell SR, Maloney DG, Turtle CJ. Feasibility and efficacy of CD19-targeted CAR T cells with concurrent ibrutinib for CLL after ibrutinib failure. Blood. 2020 May 7;135(19):1650-1660. doi: 10.1182/blood.2019002936.

  PMID: 32076701 BACKGROUND

• Fraietta JA, Beckwith KA, Patel PR, Ruella M, Zheng Z, Barrett DM, Lacey SF, Melenhorst JJ, McGettigan SE, Cook DR, Zhang C, Xu J, Do P, Hulitt J, Kudchodkar SB, Cogdill AP, Gill S, Porter DL, Woyach JA, Long M, Johnson AJ, Maddocks K, Muthusamy N, Levine BL, June CH, Byrd JC, Maus MV. Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia. Blood. 2016 Mar 3;127(9):1117-27. doi: 10.1182/blood-2015-11-679134. Epub 2016 Jan 26.

  PMID: 26813675 BACKGROUND

• Cameron F, Sanford M. Ibrutinib: first global approval. Drugs. 2014 Feb;74(2):263-71. doi: 10.1007/s40265-014-0178-8.

  PMID: 24464309 BACKGROUND

• Luo W, Zhang Y, Li C, Xu J, Wu Z, Wang X, Kang Y, Liao D, Kou H, Xie W, Xiong W, Deng J, Mei H, Hu Y. BTK Inhibitor Synergizes With CD19-Targeted Chimeric Antigen Receptor-T Cells in Patients With Relapsed or Refractory B-Cell Lymphoma: An Open-Label Pragmatic Clinical Trial. Cancer Med. 2025 Oct;14(20):e71321. doi: 10.1002/cam4.71321.

  PMID: 41123227 DERIVED

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Burkitt Lymphoma; Lymphoma, Follicular; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Yu Hu

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heng Mei

CONTACT

027-8572600; hmei@hust.edu.cn

Wenjing Luo

CONTACT

15927552323; weerfi@hust.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Proferssor, Cheif Doctor

Model Details: This study was a pragmatic clinical trial in which patients were divided into two groups, one receiving anti-CD19 CAR-T cells infusion, the other group receiving anti-CD19 CAR-T cells infusion and concurrent oral BTK inhibitor.

Study Record Dates

• First Submitted: August 19, 2021
• First Posted: August 25, 2021
• Study Start: September 14, 2021
• Primary Completion: October 13, 2023
• Study Completion: October 13, 2024
• Last Updated: July 25, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)