LeukemiaPhase 1NCT04014894
ET019003-T Cells in Relapsed/Refractory CD19+ B-Cell Leukemia and Lymphoma
A Phase 1 study testing ET019003-T Cells in people with Leukemia and Lymphoma, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- What is being tested?
- ET019003-T Cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteChina
- Study dates
- 12 Jun 2019to 1 Jul 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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.
- Failure to achieve CR or relapse after one line or multiple lines of salvage chemotherapy.
- Not suitable for hematopoietic stem cell transplantation (HSCT), or abandon HSCT due to various restrictions, or relapse after HSCT.
Show all 17Show fewer
- 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.
- 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:
- Patients with lymphoma require a single lesion≥15mm or 2 or more lesions≥10mm.
- Patients with leukemia require persistent positive or positive relapse of bone marrow MRD.
- Patient's main organs functioning well:
- Liver function: ALT/AST ≤ 3 times the upper limit of normal (ULN) and total bilirubin≤2 times ULN.
- 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.
Who cannot join
- 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.
Show all 13Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430022
About this study
Official title: Safety and Efficiency Study of ET019003-T Cells in Relapsed/Refractory CD19+ B-Cell Leukemia and Lymphoma
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.
Read the 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.
- Being tested
- ET019003-T Cells
- Medical subject headings
- Leukemia, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ET019003-T CellsDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| ET019003-T Cells | Experimental | The trial will enroll 9 patients with leukemia and 9 patients with lymphoma. Each disease has 3 dose-levels. Receives: Drug: ET019003-T Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 3 years
Secondary outcomes (6)
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).
Measured: 3 years
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).
Measured: 3 years
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).
Measured: 3 years
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).
Measured: 3 years
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.
Measured: 3 years
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.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2019
- Study start12 Jun 2019
- Primary completion1 Jul 2021
- Study completion1 Jul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 9 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Eureka(Beijing) Biotechnology Co., Ltd.
- Responsible party
- Principal investigator, MEI HENG, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Investigators
- Heng Mei, M.D., Ph.D, Principal investigator, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04014894
- Sponsor's protocol ID
- ET019003-T
- Status last verified
- Nov 2021
- First submitted
- 2 Jul 2019
- Last updated
- 12 Nov 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 30501490Maude 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.
PubMed 29385370Neelapu 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.
PubMed 29226797Xu 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.
PubMed 30479831Li 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.
PubMed 36681817
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficiency Study of ET019003-T Cells in Relapsed/Refractory CD19+ B-Cell Leukemia and Lymphoma
- ClinicalTrials.gov ID
- NCT04014894
- Acronym / sponsor ID
- ET019003-T
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 9 participants (estimated)
- Lead sponsor
- Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyUniversity, hospital or other
- Collaborators
- Eureka(Beijing) Biotechnology Co., Ltd.
- Study start
- 12 Jun 2019 (actual)
- Primary completion
- 1 Jul 2021 (actual)
- Study completion
- 1 Jul 2022 (estimated)
- First posted
- 10 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| ET019003-T Cells | Experimental | Drug: ET019003-T CellsThe trial will enroll 9 patients with leukemia and 9 patients with lymphoma. Each disease has 3 dose-levels. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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.
- Having a measurable or evaluable lesion:
- Patient's main organs functioning well:
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ET019003-T CellsFludarabine 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. | Drug | ET019003-T Cells |
Primary outcome
Incidence of Treatment-related Adverse Events
Time frame: 3 years
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).
6 secondary outcomes
Overall Remission Rate(ORR) of ET019003-T cells in Leukemia and Lymphoma
Time frame: 3 years
Overall survival(OS) of ET019003-T cells in Leukemia and Lymphoma
Time frame: 3 years
Progress-free survival(PFS) of ET019003-T cells in Leukemia and Lymphoma
Time frame: 3 years
duration of Response(DOR) of ET019003-T cells in Leukemia and Lymphoma
Time frame: 3 years
Rate of ET019003-T cells in bone marrow cells and peripheral blood cells
Time frame: 3 years
Quantity of ET019003-T CAR copies in bone marrow cells and peripheral blood cells
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2021.
- Background: PubMed 30501490Schuster 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.
- Background: PubMed 29385370Maude 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.
- Background: PubMed 29226797Neelapu 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.
- Background: PubMed 30479831Xu 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.
- Derived from this study: PubMed 36681817Li 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.
Related trials for Leukemia
Not yet recruitingPhase 2
Nemtabrutinib for Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL) Refractory to Covalent Bruton Tyrosine Kinase Inhibitor or Pirtobrutinib and Previously Treated With a BCL2 Inhibitor
Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia
Not yet recruitingPhase 1
huCART19-IL18-CD428z Cells for the Treatment of Patients With HIV With CD19+ Cancers
Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
RecruitingPhase 1
Anti-CRLF2-R/TSLPR Chimeric Antigen Receptor T Cells (TSLPR-CART) in Participants With Recurrent or Refractory CRLF2-R/TSLPR-Overexpressing B-Cell Acute Lymphoblastic Leukemia (B-ALL)
B-All, Acute Lymphoblastic Leukemia
RecruitingPhase 1/2
Phase Ib/II Trial of Cladribine/Ruxolitinib/Venetoclax in Patients With Relapsed/Refractory T-cell Prolymphocytic Leukemia
T-cell Prolymphocytic Leukemia, Refractory T-Cell Prolymphocytic Leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Heng Mei, M.D., Ph.D principal investigator
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ET019003-T Cells in people with Leukemia and Lymphoma, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-related Adverse Events (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04014894, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2021.