Back to resultsET019003-T Cells in Relapsed/Refractory CD19+ B-Cell Leukemia and Lymphoma
Primary Purpose
Leukemia, Lymphoma
Status
Active
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
ET019003-T Cells
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia
Eligibility Criteria
Inclusion Criteria:
- Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
- Male or female, aged 18 to 75 years (including 18 and 75 years old).
Pathologically confirmed CD19+ B-cell malignancies, and patients met the following criteria for refractory or relapsed B-cell malignancies.
A. Refractory/relapsed B-cell lymphoblastic leukemia (meeting one of the following) i. Recurrence within 6 months after first remission. ii. Primary refractory disease which cannot achieve complete remission (CR) after 2 cycles of standardized chemotherapy regimen.
iii. Failure to achieve CR or relapse after one line or multiple lines of salvage chemotherapy.
iv. Not suitable for hematopoietic stem cell transplantation (HSCT), or abandon HSCT due to various restrictions, or relapse after HSCT.
B. Refractory/relapsed B-cell lymphoma (Meeting 1 of the first 3 items plus item 4) i. Tumor shrinkage less than 50% or disease progression after 4 cycles of standard chemotherapy.
ii. Achieved CR after standard chemotherapy, but relapsed within 6 months. iii. Two or more relapses after CR. iv. Subjects must have received adequate treatment in the past, including anti-CD20 monoclonal antibody and combination chemotherapy with anthracyclines.
Having a measurable or evaluable lesion:
A. Patients with lymphoma require a single lesion≥15mm or 2 or more lesions≥10mm.
B. Patients with leukemia require persistent positive or positive relapse of bone marrow MRD.
Patient's main organs functioning well:
A. Liver function: ALT/AST ≤ 3 times the upper limit of normal (ULN) and total bilirubin≤2 times ULN.
B. Renal function: Creatinine < 220μmol/L. C. Pulmonary function: Indoor oxygen saturation≥95%. D. Cardiac Function: Left ventricular ejection fraction (LVEF) ≥ 50%.
- ≥ 2 weeks since prior therapy at the time of enrollment, and the toxicity related to previous treatments returned to < grade 1 (except for low grade toxicity such as alopecia).
- ECOG score≤ 2.
- Estimated survival time≥3 months.
Exclusion Criteria:
- Women who are pregnant or breastfeeding.
- Women of child-bearing potential and all male participants can't use effective methods of contraception for at least 12 months following infusion.
- Patients fail to collect enough PBMC.
- Patients with other uncontrolled diseases, such as active infections.
- Active hepatitis B or active hepatitis C.
- Known HIV positive patients.
- Patients with active autoimmune diseases requiring systemic immunosuppressive therapy.
- Participants with other active malignancies (except non-melanoma skin cancer and cervical cancer) within 3 years.
- Patients with severe mental disorder or disorders of consciousness.
- Patients who need immediate treatment to control tumor progression or relieve tumor burden.
- Patients participated in other clinical treatments within 6 weeks.
- Patients with drug addiction.
- Patients with poor treatment compliance.
Sites / Locations
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ET019003-T Cells
Arm Description
The trial will enroll 9 patients with leukemia and 9 patients with lymphoma. Each disease has 3 dose-levels.
Outcomes
Primary Outcome Measures
Incidence of Treatment-related Adverse Events
Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0).
Secondary Outcome Measures
Overall Remission Rate(ORR) of ET019003-T cells in Leukemia and Lymphoma
ORR will be assessed from the first CAR-T cell infusion to death or last follow-up (censored).
Overall survival(OS) of ET019003-T cells in Leukemia and Lymphoma
OS will be assessed from the first CAR-T cell infusion to death or last follow-up (censored).
Progress-free survival(PFS) of ET019003-T cells in Leukemia and Lymphoma
PFS will be assessed from the first CAR-T cell infusion to death or last follow-up (censored).
duration of Response(DOR) of ET019003-T cells in Leukemia and Lymphoma
DOR will be assessed from the first CAR-T cell infusion to death or last follow-up (censored).
Rate of ET019003-T cells in bone marrow cells and peripheral blood cells
In vivo (bone marrow and peripheral blood) rate of ET019003-T cells were determined by means of flow cytometry.
Quantity of ET019003-T CAR copies in bone marrow cells and peripheral blood cells
In vivo (bone marrow and peripheral blood) quantity of ET019003-T CAR copies copies were determined by means of qPCR.
Full Information
NCT ID
NCT04014894
First Posted
July 2, 2019
Last Updated
November 11, 2021
Sponsor
Wuhan Union Hospital, China
Collaborators
Eureka(Beijing) Biotechnology Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04014894
Brief Title
ET019003-T Cells in Relapsed/Refractory CD19+ B-Cell Leukemia and Lymphoma
Official Title
Safety and Efficiency Study of ET019003-T Cells in Relapsed/Refractory CD19+ B-Cell Leukemia and Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 12, 2019 (Actual)
Primary Completion Date
July 1, 2021 (Actual)
Study Completion Date
July 1, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Wuhan Union Hospital, China
Collaborators
Eureka(Beijing) Biotechnology Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a single center, open-label, 3+3 dose escalation, phase 1 study to evaluate the efficacy and safety of ET019003-T cells therapy for patients with relapsed/refractory CD19+ acute lymphoblastic leukemia and lymphoma.
Detailed Description
ET019003-T cells is a human anti-CD19 CAR-T cells by fusing the anti-CD19 antibody Fab domain with the transmembrane and intracellular domains from the γδTCR, which can avoid mispairing with the T cell's endogenous αβTCR chains. Meanwhile, an independent ET190L1-CSR(Chimeric Signaling Receptor) is added to ET019003-T cells in trans, which can bind CD19 to activate a novel costimulatory domain to further promote T cell proliferation and persistence.
The trial is conducted to explore the safety and efficacy of ET019003-T cells in CD19+ Leukemia and Lymphoma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
This study was a single-center, open-label, single-arm, non-randomized,3+3 dose escalation clinical trial.18 patients are separated into 9 leukemia and 9 lymphoma. Each disease has 3 groups by infusion dose level. Each dose group has 3 patients.If no DLT emerges in the group, then the next group uses the subsequent higher dose. If DLT emerges in a single subject in any dose level, 3 more subjects will be enrolled to the same dose level.The maximum dose could be extended.
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ET019003-T Cells
Arm Type
Experimental
Arm Description
The trial will enroll 9 patients with leukemia and 9 patients with lymphoma. Each disease has 3 dose-levels.
Intervention Type
Drug
Intervention Name(s)
ET019003-T Cells
Intervention Description
Fludarabine 25 mg/day on day -5, -4 and -3; Cyclophosphamide 250 or 300 mg/day on day -5, -4 and -3; ET019003-T Cells on day 0.
Primary Outcome Measure Information:
Title
Incidence of Treatment-related Adverse Events
Description
Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0).
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Overall Remission Rate(ORR) of ET019003-T cells in Leukemia and Lymphoma
Description
ORR will be assessed from the first CAR-T cell infusion to death or last follow-up (censored).
Time Frame
3 years
Title
Overall survival(OS) of ET019003-T cells in Leukemia and Lymphoma
Description
OS will be assessed from the first CAR-T cell infusion to death or last follow-up (censored).
Time Frame
3 years
Title
Progress-free survival(PFS) of ET019003-T cells in Leukemia and Lymphoma
Description
PFS will be assessed from the first CAR-T cell infusion to death or last follow-up (censored).
Time Frame
3 years
Title
duration of Response(DOR) of ET019003-T cells in Leukemia and Lymphoma
Description
DOR will be assessed from the first CAR-T cell infusion to death or last follow-up (censored).
Time Frame
3 years
Title
Rate of ET019003-T cells in bone marrow cells and peripheral blood cells
Description
In vivo (bone marrow and peripheral blood) rate of ET019003-T cells were determined by means of flow cytometry.
Time Frame
3 years
Title
Quantity of ET019003-T CAR copies in bone marrow cells and peripheral blood cells
Description
In vivo (bone marrow and peripheral blood) quantity of ET019003-T CAR copies copies were determined by means of qPCR.
Time Frame
3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
Male or female, aged 18 to 75 years (including 18 and 75 years old).
Pathologically confirmed CD19+ B-cell malignancies, and patients met the following criteria for refractory or relapsed B-cell malignancies.
A. Refractory/relapsed B-cell lymphoblastic leukemia (meeting one of the following) i. Recurrence within 6 months after first remission. ii. Primary refractory disease which cannot achieve complete remission (CR) after 2 cycles of standardized chemotherapy regimen.
iii. Failure to achieve CR or relapse after one line or multiple lines of salvage chemotherapy.
iv. Not suitable for hematopoietic stem cell transplantation (HSCT), or abandon HSCT due to various restrictions, or relapse after HSCT.
B. Refractory/relapsed B-cell lymphoma (Meeting 1 of the first 3 items plus item 4) i. Tumor shrinkage less than 50% or disease progression after 4 cycles of standard chemotherapy.
ii. Achieved CR after standard chemotherapy, but relapsed within 6 months. iii. Two or more relapses after CR. iv. Subjects must have received adequate treatment in the past, including anti-CD20 monoclonal antibody and combination chemotherapy with anthracyclines.
Having a measurable or evaluable lesion:
A. Patients with lymphoma require a single lesion≥15mm or 2 or more lesions≥10mm.
B. Patients with leukemia require persistent positive or positive relapse of bone marrow MRD.
Patient's main organs functioning well:
A. Liver function: ALT/AST ≤ 3 times the upper limit of normal (ULN) and total bilirubin≤2 times ULN.
B. Renal function: Creatinine < 220μmol/L. C. Pulmonary function: Indoor oxygen saturation≥95%. D. Cardiac Function: Left ventricular ejection fraction (LVEF) ≥ 50%.
≥ 2 weeks since prior therapy at the time of enrollment, and the toxicity related to previous treatments returned to < grade 1 (except for low grade toxicity such as alopecia).
ECOG score≤ 2.
Estimated survival time≥3 months.
Exclusion Criteria:
Women who are pregnant or breastfeeding.
Women of child-bearing potential and all male participants can't use effective methods of contraception for at least 12 months following infusion.
Patients fail to collect enough PBMC.
Patients with other uncontrolled diseases, such as active infections.
Active hepatitis B or active hepatitis C.
Known HIV positive patients.
Patients with active autoimmune diseases requiring systemic immunosuppressive therapy.
Participants with other active malignancies (except non-melanoma skin cancer and cervical cancer) within 3 years.
Patients with severe mental disorder or disorders of consciousness.
Patients who need immediate treatment to control tumor progression or relieve tumor burden.
Patients participated in other clinical treatments within 6 weeks.
Patients with drug addiction.
Patients with poor treatment compliance.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Heng Mei, M.D., Ph.D
Organizational Affiliation
Wuhan Union Hospital, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430022
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
30501490
Citation
Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, Jager U, Jaglowski S, Andreadis C, Westin JR, Fleury I, Bachanova V, Foley SR, Ho PJ, Mielke S, Magenau JM, Holte H, Pantano S, Pacaud LB, Awasthi R, Chu J, Anak O, Salles G, Maziarz RT; JULIET Investigators. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2019 Jan 3;380(1):45-56. doi: 10.1056/NEJMoa1804980. Epub 2018 Dec 1.
Results Reference
background
PubMed Identifier
29385370
Citation
Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M, De Moerloose B, Hiramatsu H, Schlis K, Davis KL, Martin PL, Nemecek ER, Yanik GA, Peters C, Baruchel A, Boissel N, Mechinaud F, Balduzzi A, Krueger J, June CH, Levine BL, Wood P, Taran T, Leung M, Mueller KT, Zhang Y, Sen K, Lebwohl D, Pulsipher MA, Grupp SA. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med. 2018 Feb 1;378(5):439-448. doi: 10.1056/NEJMoa1709866.
Results Reference
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PubMed Identifier
29226797
Citation
Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. doi: 10.1056/NEJMoa1707447. Epub 2017 Dec 10.
Results Reference
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PubMed Identifier
30479831
Citation
Xu Y, Yang Z, Horan LH, Zhang P, Liu L, Zimdahl B, Green S, Lu J, Morales JF, Barrett DM, Grupp SA, Chan VW, Liu H, Liu C. A novel antibody-TCR (AbTCR) platform combines Fab-based antigen recognition with gamma/delta-TCR signaling to facilitate T-cell cytotoxicity with low cytokine release. Cell Discov. 2018 Nov 20;4:62. doi: 10.1038/s41421-018-0066-6. eCollection 2018.
Results Reference
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ET019003-T Cells in Relapsed/Refractory CD19+ B-Cell Leukemia and Lymphoma
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