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RecruitingNCT05020392Updated Jul 25, 2023

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

A Phase 3 interventional study of BTK inhibitor+ Fludarabine-based chemotherapy + CAR-T-CD19 Cells and Fludarabine-based chemotherapy + CAR-T-CD19 Cells in Diffuse Large B Cell Lymphoma, Burkitt Lymphoma and Follicular Lymphoma, sponsored by Wuhan Union Hospital, China. Recruiting at 1 site in China. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2023-07-25.

Sponsored by Wuhan Union Hospital, China · Phase 3, Interventional, and Treatment

From the registry’s dates

  • Primary completion was expected by Oct 2023, 2 years 11 months ago, but the record still lists the study as recruiting.
  • Started Sep 2021; still recruiting 5 years later.
Phase
Phase 3
Study type
Interventional
Enrollment
24
Allocation
Non-randomized
Ages
18 Years to 70 Years
Sex
All
01

Study 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

Read the 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.

02

Conditions studied

  • Diffuse Large B Cell Lymphoma
  • Burkitt Lymphoma
  • Follicular Lymphoma
  • Chronic Lymphocytic Leukemia
  • Mantle Cell Lymphoma
03

In context

Burkitt Lymphoma

392 studies on the registry are indexed under Burkitt Lymphoma; 114 are open to participants now.

This study's planned enrollment of 24 is below the median of 41 across 354 interventional studies indexed under Burkitt Lymphoma.

Browse Burkitt Lymphoma studies →

Lead sponsor

Wuhan Union Hospital, China is the lead sponsor of 230 studies on the registry; 104 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

-

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.

    -

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
24 participants (estimated)

Study arms

  • 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

  • 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

Interventions

  • DrugBTK 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.

  • DrugFludarabine-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.

06

What researchers measure

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).

    Time frame: within 2 years after infusion

Secondary outcomes

  1. 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.

    ORR will be assessed from CAR-T cell infusion to death or last follow-up (censored).

    Time frame: within 2 years after infusion

  2. 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.

    DOR will be assessed from CAR-T cell infusion to death or last follow-up (censored).

    Time frame: within 2 years after infusion

  3. 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.

    OS will be assessed from CAR-T cell infusion to death or last follow-up (censored).

    Time frame: within 2 years after infusion

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

    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.

    Time frame: within 2 years after infusion

  5. 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.

    CR will be assessed from CAR-T cell infusion to death or last follow-up (censored).

    Time frame: within 2 years after infusion

  6. 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.

    PR will be assessed from CAR-T cell infusion to death or last follow-up.

    Time frame: within 2 years after infusion

Other outcomes

  1. In vivo expansion and survival of CAR-T-CD19 cells

    Quantity of CAR-T-CD19 CAR copies in bone marrow, peripheral blood and cerebrospinal fluid will be determined by using quantitative polymerase chain reaction.

    Time frame: within 2 years after infusion

07

Study locations

1 of 1 sites recruiting
  • Union Hospital, Huazhong University of Science and Technology
    Wuhan, Hubei 430022, China
    Recruiting
08

References and documents

Publications

  • 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. PubMed 32076701 ↗
  • 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. PubMed 26813675 ↗
  • Cameron F, Sanford M. Ibrutinib: first global approval. Drugs. 2014 Feb;74(2):263-71. doi: 10.1007/s40265-014-0178-8. PubMed 24464309 ↗

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 25, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05020392
Lead sponsor
Wuhan Union Hospital, China
Collaborators
Wuhan Si'an Medical Technology Co., Ltd
Responsible party
MEI HENG (Proferssor, Cheif Doctor, Wuhan Union Hospital, China) — Principal investigator
First posted
Aug 25, 2021
Start date
Sep 14, 2021
Primary completion
Oct 13, 2023 (estimated)
Completion
Oct 13, 2024 (estimated)
Last update
Jul 25, 2023

Study contacts

Heng Mei
Contact
hmei@hust.edu.cn
027-8572600
Wenjing Luo
Contact
weerfi@hust.edu.cn
15927552323
Yu Hu
principal investigator · Wuhan Union Hospital, China

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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