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

July 23, 2023 updated by: MEI HENG, Wuhan Union Hospital, China

Efficacy and Safety of Autologous Cells Derived Anti-CD19 CAR-Engineered T Cells With Concurrent BTK Inhibitor for B Cell Lymphoma：a Single-center, Open-label, Pragmatic Clinical Trial

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Anti-CD19 chimeric antigen receptor (CAR) T-cell has shown dramatical efficacy in B cell malignancies. And Bruton tyrosine kinase (BTK) inhibitor agents have been validated as an effective drug to treat B cell malignancies. Combined therapies comprising ibrutinib (a BTK inhibitor) and anti-CD19 CAR-T cells in patients with CLL after ibrutinib failure are considered feasible and safe.

Ibrutinib is the first-generation BTK inhibitror and Zanubrutinib is the second-generation BTK inhibitor. Orelabrutinib is a newly developed BTK inhibitor with high selectivity and have received its approval in China. Autologous cells derived T cells are purified and transduced with a lentiviral vector encoding the humanized CD19 scFv.

To evaluate whether the addition of BTK inhibitor (Ibrutinib, Zanubrutinib and Orelabrutinib) in anti-CD19 CAR-T cells therapy would further improve efficacy and safety, we intend to conduct this pragmatic clinical trial.

Study Type

Interventional

Enrollment (Estimated)

24

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Hubei
      • Wuhan, Hubei, China, 430022
        • Recruiting
        • Union Hospital, Huazhong University of Science and Technology
        • Contact:
        • Contact:
        • Principal Investigator:
          • Yu Hu, M.D., Ph.D

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Aged ≥ 18 years and ≤70 years.
  2. Expected survival over 6 months.
  3. Eastern Cooperative Oncology Group score≤ 2.
  4. 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.
  5. Patients have failed at least 1 line of prior therapy
  6. Negativity of blood pregnancy test for woman, and participants use effective methods of contraception until last follow-up.

  7. Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.

    -

Exclusion Criteria:

  1. 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.
  2. Existing or preexisting CNS conditions, such as epileptic seizures, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any CNS related autoimmune diseases.
  3. Patients with graft-versus-host reaction and need immunosuppressive agents, or patients with autoimmune diseases.
  4. Participants with other active malignancies (except non-melanoma skin cancer and cervical cancer) within five years.
  5. History of Richter's syndrome.
  6. 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.
  7. Patients who are pregnant or breast-feeding.

  8. 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).

  9. Major surgery within 4 weeks of randomization.
  10. Systemic steroids are used within 2 weeks before apheresis (Except for those who are using inhaled steroids recently or currently).
  11. 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).
  12. Prior treatment with any gene therapy product.
  13. Active hepatitis B, active hepatitis C, or active human immunodeficiency virus (HIV) infection.
  14. Systemic fungal, bacterial, viral, or other infection that is not controlled.
  15. The absolute value of lymphocytes was too low to manufacture CAR-T cells.

  16. Other conditions considered inappropriate by the researcher.

    -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Effective of CAR-T-CD19 cells with concurrent BTK inhibitor
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
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.
Active Comparator: Effective of CAR-T-CD19 cells monotherapy
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
Fludarabine-based lymphodepletion chemotherapy was followed by CART19 infusion at a dose of 1x10^6/kg on day 0 and day 1 respectively.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Treatment-related Adverse Events
Time Frame: within 2 years after infusion
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: within 2 years after infusion
ORR will be assessed from CAR-T cell infusion to death or last follow-up (censored).
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.
Time Frame: within 2 years after infusion
DOR will be assessed from CAR-T cell infusion to death or last follow-up (censored).
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.
Time Frame: within 2 years after infusion
OS will be assessed from CAR-T cell infusion to death or last follow-up (censored).
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.
Time Frame: within 2 years after infusion
CR will be assessed from CAR-T cell infusion to death or last follow-up (censored).
within 2 years after infusion
Partial response rate (PR) of administering CAR-T-CD19 cells or CAR-T-CD19 cells with oral BTK inhibitor in Relapsed/Refractory B cell lymphoma.
Time Frame: within 2 years after infusion
PR will be assessed from CAR-T cell infusion to death or last follow-up.
within 2 years after infusion
PFS will be assessed from CAR-T cell infusion to death or last follow-up
Time Frame: within 2 years after infusion
Progress-free survival (PFS) 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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
In vivo expansion and survival of CAR-T-CD19 cells
Time Frame: within 2 years after infusion
Quantity of CAR-T-CD19 CAR copies in bone marrow, peripheral blood and cerebrospinal fluid will be determined by using quantitative polymerase chain reaction.
within 2 years after infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wuhan Union Hospital, China

Collaborators

Wuhan Si'an Medical Technology Co., Ltd

Investigators

  • Principal Investigator: Yu Hu, Wuhan Union Hospital, China

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 14, 2021

Primary Completion (Estimated)

October 13, 2023

Study Completion (Estimated)

October 13, 2024

Study Registration Dates

First Submitted

August 19, 2021

First Submitted That Met QC Criteria

August 19, 2021

First Posted (Actual)

August 25, 2021

Study Record Updates

Last Update Posted (Actual)

July 25, 2023

Last Update Submitted That Met QC Criteria

July 23, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • auto-CART-CD19 cells and BTKi

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

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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