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ET019003-T Cells in Relapsed/Refractory CD19+ B-Cell Leukemia and Lymphoma

NCT ID: NCT04014894

Last Updated: 2021-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-06-12

Study Completion Date

2022-07-01

Brief Summary

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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

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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.

Conditions

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Leukemia Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ET019003-T Cells

The trial will enroll 9 patients with leukemia and 9 patients with lymphoma. Each disease has 3 dose-levels.

Group Type EXPERIMENTAL

ET019003-T Cells

Intervention Type DRUG

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.

Interventions

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ET019003-T Cells

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
2. Male or female, aged 18 to 75 years (including 18 and 75 years old).
3. 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.
4. 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.
5. 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%.
6. ≥ 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).
7. ECOG score≤ 2.
8. Estimated survival time≥3 months.

Exclusion Criteria

1. Women who are pregnant or breastfeeding.
2. Women of child-bearing potential and all male participants can't use effective methods of contraception for at least 12 months following infusion.
3. Patients fail to collect enough PBMC.
4. Patients with other uncontrolled diseases, such as active infections.
5. Active hepatitis B or active hepatitis C.
6. Known HIV positive patients.
7. Patients with active autoimmune diseases requiring systemic immunosuppressive therapy.
8. Participants with other active malignancies (except non-melanoma skin cancer and cervical cancer) within 3 years.
9. Patients with severe mental disorder or disorders of consciousness.
10. Patients who need immediate treatment to control tumor progression or relieve tumor burden.
11. Patients participated in other clinical treatments within 6 weeks.
12. Patients with drug addiction.
13. Patients with poor treatment compliance.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eureka(Beijing) Biotechnology Co., Ltd.

UNKNOWN

Sponsor Role collaborator

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

OTHER

Sponsor Role lead

Responsible Party

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MEI HENG

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Heng Mei, M.D., Ph.D

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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

Wuhan, Hubei, China

Site Status

Countries

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China

References

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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.

Reference Type BACKGROUND
PMID: 30501490 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29385370 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29226797 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30479831 (View on PubMed)

Li C, Zhou F, Wang J, Chang Q, Du M, Luo W, Zhang Y, Xu J, Tang L, Jiang H, Liu L, Kou H, Lu C, Liao D, Wu J, Wei Q, Ke S, Deng J, Liu C, Mei H, Hu Y. Novel CD19-specific gamma/delta TCR-T cells in relapsed or refractory diffuse large B-cell lymphoma. J Hematol Oncol. 2023 Jan 21;16(1):5. doi: 10.1186/s13045-023-01402-y.

Reference Type DERIVED
PMID: 36681817 (View on PubMed)

Other Identifiers

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ET019003-T

Identifier Type: -

Identifier Source: org_study_id