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

NCT04014894 | Unknown Phase 1

• 1 other identifier: ET019003-T
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Leukemia; Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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).

  3 years

Secondary Outcomes (6)

• Overall Remission Rate(ORR) of ET019003-T cells in Leukemia and Lymphoma

  3 years

• Overall survival(OS) of ET019003-T cells in Leukemia and Lymphoma

  3 years

• Progress-free survival(PFS) of ET019003-T cells in Leukemia and Lymphoma

  3 years

• duration of Response(DOR) of ET019003-T cells in Leukemia and Lymphoma

  3 years

• Rate of ET019003-T cells in bone marrow cells and peripheral blood cells

  3 years

Study Arms (1)

ET019003-T Cells

EXPERIMENTAL

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

Drug: ET019003-T Cells

Interventions

ET019003-T Cells 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.

ET019003-T Cells

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead
• Eureka(Beijing) Biotechnology Co., Ltd.: collaborator

Study Sites (1)

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

Wuhan, Hubei, 430022, China

Location

Related Publications (5)

• 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.

  PMID: 30501490 BACKGROUND

• 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.

  PMID: 29385370 BACKGROUND

• 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.

  PMID: 29226797 BACKGROUND

• 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.

  PMID: 30479831 BACKGROUND

• 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.

  PMID: 36681817 DERIVED

MeSH Terms

Conditions

Leukemia; Lymphoma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Heng Mei, M.D., Ph.D

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: July 2, 2019
• First Posted: July 10, 2019
• Study Start: June 12, 2019
• Primary Completion: July 1, 2021
• Study Completion: July 1, 2022
• Last Updated: November 12, 2021

Record last verified: 2021-11

Locations

CN (1)