Autologous Cells Derived Anti-CD19 CAR-Engineered T Cells With Concurrent BTK Inhibitor for B Cell Lymphoma
NCT ID: NCT05020392
Last Updated: 2023-07-25
Study Results
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Basic Information
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UNKNOWN
PHASE3
24 participants
INTERVENTIONAL
2021-09-14
2024-10-13
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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.
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.
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.
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.
Interventions
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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.
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.
Eligibility Criteria
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Inclusion Criteria
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.
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Exclusion Criteria
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.
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18 Years
70 Years
ALL
No
Sponsors
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Wuhan Si'an Medical Technology Co., Ltd
UNKNOWN
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
OTHER
Responsible Party
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MEI HENG
Proferssor, Cheif Doctor
Principal Investigators
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Yu Hu
Role: PRINCIPAL_INVESTIGATOR
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Locations
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Union Hospital, Huazhong University of Science and Technology
Wuhan, Hubei, China
Countries
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Central Contacts
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Facility Contacts
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References
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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.
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.
Cameron F, Sanford M. Ibrutinib: first global approval. Drugs. 2014 Feb;74(2):263-71. doi: 10.1007/s40265-014-0178-8.
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.
Other Identifiers
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auto-CART-CD19 cells and BTKi
Identifier Type: -
Identifier Source: org_study_id
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