Non-hodgkin Lymphoma,B CellPhase 1/2Trident19-HNCT03497533
Treatment of Refractory/Relapsed Non-Hodgkin Lymphoma With TriCAR-T_CD19
A Phase 1/2 study testing TriCAR-T-CD19 in people with Non-hodgkin Lymphoma,B Cell, run by Timmune Biotech Inc. at 1 site in China.
Trial summary
This is a single arm, open-label, single-center, phase 1/2 study, to determine the safety and efficacy of TriCAR-T-CD19, an autologous tri-functional anti-CD19 chimeric antigen receptor (CAR)-positive T cell therapy, in refractory/Relapsed Non-Hodgkin Lymphoma (NHL). Read more about this study
- Who is it for?
- Ages 18 to 68 years
- Conditions the study is for
- Non-hodgkin Lymphoma,B Cell
- What is being tested?
- TriCAR-T-CD19
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteChina
- Study dates
- 3 Aug 2018to 31 Dec 2020
- Phase
- Phase 1/2
- 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 68 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All subjects must personally sign and date the consent form before initiating any study specific procedures or activities;
- All subjects must be able to comply with all the scheduled procedures in the study;
- Histologically or cytologically confirmed CD19 positive non-Hodgkin lymphoma;
- Chemotherapy-refractory disease, defined as one or more of the following: Relapsed in 6 months after most recent therapy; Progressive disease in the standard R-CHOP or CHOP chemotherapy; Disease progression or relapsed in ≤12 months of ASCT (must have biopsy proven recurrence in relapsed subjects); If salvage therapy is given post-ASCT, the subject must have had no response to or relapsed after the last line of therapy.
- No available standard therapy;
- At least one measurable lesion per revised IWG Response Criteria;
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- Aged 18 to 68 years;
- Expected survival ≥12 weeks;
- Eastern cooperative oncology group (ECOG) performance status of ≤2;
- Systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks;
- All other treatment induced adverse events must have been resolved to ≤grade 1;
- Laboratory tests must fulfill the following criteria: ANC ≥ 1000/uL, HGB >70g/L, Platelet count ≥ 50,000/uL, Creatinine clearance ≤1.5 ULN, Serum ALT/AST ≤2.5 ULN, Total bilirubin ≤1.5 ULN (except in subjects with Gilbert's syndrome);
- Female must be not pregnant during the study.
Who cannot join
- History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3 years;
- History of allogeneic stem cell transplantation;
- Prior other CAR therapy or other genetically modified T cell therapy;
- Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment;
- Subjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases;
- Lactating women;
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- Active infection with hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive);
- Subjects need systematic usage of corticosteroid;
- History of any gene therapy;
- Subjects need systematic usage of immunosuppressive drug;
- Known history of infection with HIV;
- Planed operation, history of other related disease, or any other related laboratory tests restrict patients for the study;
- Other reasons the investigator think the patient may not be suitable for the study.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Hunan Provincial People's Hospital
Changsha, Hunan, 410005
Jianjun Chen, +86 0731 83928147
Ming Zhou, +86 0731 83928145, zhouming_0321@163.com
About this study
Official title: TriCAR-T-CD19 Adoptive Immunotherapy for CD19-positive Refractory/Relapsed Non-Hodgkin Lymphoma
This is a single arm, open-label, single-center, phase 1/2 study, to determine the safety and efficacy of TriCAR-T-CD19, an autologous tri-functional anti-CD19 chimeric antigen receptor (CAR)-positive T cell therapy, in refractory/Relapsed Non-Hodgkin Lymphoma (NHL).
Read the detailed description
The tri-functional anti-CD19 chimeric antigen receptor contains an anti-CD19 scFv, a PD-L1 blocker, and a cytokine complex, enabling the TriCAR-T-CD19 to simultaneously targeting the CD19 positive NHL，blocking the inhibitory PD-L1 signal and stimulating T/NK cell activation and expansion.
- Conditions
- Non-hodgkin Lymphoma,B Cell
- Being tested
- TriCAR-T-CD19
- Keywords
- CD19, CAR-T, TriCAR-T-CD19, non-Hodgkin lymphoma, NHL
- Medical subject headings
- Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TriCAR-T-CD19Biological
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously at a target dose of 0.5-1 x 10^6 CAR+ T cells/kg
| Study group | Role | What they receive |
|---|---|---|
| TriCAR-T-CD19 | Experimental | Tri-functional anti-CD19 chimeric antigen receptor transduced autologous T cells will be administered intravenously Receives: Biological: TriCAR-T-CD19 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety (Incidence of treatment-related adverse events as assessed by CTCAE v4.0)
Incidence of treatment-related adverse events as assessed by CTCAE v4.0
Measured: 30 Days
Secondary outcomes (5)
Complete response rate[CR] (Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma)
Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma
Measured: 12 months
Partial response rate [PR] (Partial response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma)
Partial response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma
Measured: 12 months
Duration of Response （The time from response to relapse or progression）
The time from response to relapse or progression
Measured: 12 months
Progression Free Survival（The time from the first day of treatment to the date on which disease progresses.）
The time from the first day of treatment to the date on which disease progresses.
Measured: 12 months
Overall Survival（The number of patient alive, with or without signs of cancer）
The number of patient alive, with or without signs of cancer
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2018
- Study start3 Aug 2018
- Primary completion31 Dec 2020 (estimated)
- Study completion31 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Non-hodgkin Lymphoma,B CellStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Timmune Biotech Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Hunan Provincial People's Hospital
- Responsible party
- Sponsor
- Investigators
- Ming Zhou, Principal investigator, Hunan Provincial People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03497533
- Sponsor's protocol ID
- ChiCTR1800014528
- Acronym
- Trident19-H
- Status last verified
- Sep 2019
- First submitted
- 11 Feb 2018
- Last updated
- 6 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, June CH. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med. 2011 Aug 10;3(95):95ra73. doi: 10.1126/scitranslmed.3002842.
PubMed 21832238Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 Results of ZUMA-1: A Multicenter Study of KTE-C19 Anti-CD19 CAR T Cell Therapy in Refractory Aggressive Lymphoma. Mol Ther. 2017 Jan 4;25(1):285-295. doi: 10.1016/j.ymthe.2016.10.020. Epub 2017 Jan 4.
PubMed 28129122Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, Komanduri KV, Lin Y, Jain N, Daver N, Westin J, Gulbis AM, Loghin ME, de Groot JF, Adkins S, Davis SE, Rezvani K, Hwu P, Shpall EJ. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2018 Jan;15(1):47-62. doi: 10.1038/nrclinonc.2017.148. Epub 2017 Sep 19.
PubMed 28925994
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TriCAR-T-CD19 Adoptive Immunotherapy for CD19-positive Refractory/Relapsed Non-Hodgkin Lymphoma
- ClinicalTrials.gov ID
- NCT03497533
- Acronym / sponsor ID
- Trident19-H / ChiCTR1800014528
- Conditions
- Non-hodgkin Lymphoma,B Cell
- Keywords
- CD19, CAR-T, TriCAR-T-CD19, non-Hodgkin lymphoma, NHL
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- Timmune Biotech Inc.Industry (pharma, biotech, devices)
- Collaborators
- Hunan Provincial People's Hospital
- Study start
- 3 Aug 2018 (actual)
- Primary completion
- 31 Dec 2020 (estimated)
- Study completion
- 31 Dec 2020 (estimated)
- First posted
- 13 Apr 2018 (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 arm, open-label, single-center, phase 1/2 study, to determine the safety and efficacy of TriCAR-T-CD19, an autologous tri-functional anti-CD19 chimeric antigen receptor (CAR)-positive T cell therapy, in refractory/Relapsed Non-Hodgkin Lymphoma (NHL).
Detailed description
The tri-functional anti-CD19 chimeric antigen receptor contains an anti-CD19 scFv, a PD-L1 blocker, and a cytokine complex, enabling the TriCAR-T-CD19 to simultaneously targeting the CD19 positive NHL，blocking the inhibitory PD-L1 signal and stimulating T/NK cell activation and expansion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TriCAR-T-CD19 | Experimental | Biological: TriCAR-T-CD19Tri-functional anti-CD19 chimeric antigen receptor transduced autologous T cells will be administered intravenously |
Who may qualify
- Ages
- 18 to 68 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- All subjects must personally sign and date the consent form before initiating any study specific procedures or activities;
- All subjects must be able to comply with all the scheduled procedures in the study;
- Histologically or cytologically confirmed CD19 positive non-Hodgkin lymphoma;
- Chemotherapy-refractory disease, defined as one or more of the following: Relapsed in 6 months after most recent therapy; Progressive disease in the standard R-CHOP or CHOP chemotherapy; Disease progression or relapsed in ≤12 months of ASCT (must have biopsy proven recurrence in relapsed subjects); If salvage therapy is given post-ASCT, the subject must have had no response to or relapsed after the last line of therapy.
- No available standard therapy;
Key exclusion criteria (13 listed)
- History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3 years;
- History of allogeneic stem cell transplantation;
- Prior other CAR therapy or other genetically modified T cell therapy;
- Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment;
- Subjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases;
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 |
|---|---|---|
| TriCAR-T-CD19A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously at a target dose of 0.5-1 x 10^6 CAR+ T cells/kg | Biological | TriCAR-T-CD19 |
Primary outcome
Safety (Incidence of treatment-related adverse events as assessed by CTCAE v4.0)
Time frame: 30 Days
Incidence of treatment-related adverse events as assessed by CTCAE v4.0
5 secondary outcomes
Complete response rate[CR] (Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma)
Time frame: 12 months
Partial response rate [PR] (Partial response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma)
Time frame: 12 months
Duration of Response （The time from response to relapse or progression）
Time frame: 12 months
Progression Free Survival（The time from the first day of treatment to the date on which disease progresses.）
Time frame: 12 months
Overall Survival（The number of patient alive, with or without signs of cancer）
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2019.
- Background: PubMed 21832238Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, June CH. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med. 2011 Aug 10;3(95):95ra73. doi: 10.1126/scitranslmed.3002842.
- Results publication: PubMed 28129122Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 Results of ZUMA-1: A Multicenter Study of KTE-C19 Anti-CD19 CAR T Cell Therapy in Refractory Aggressive Lymphoma. Mol Ther. 2017 Jan 4;25(1):285-295. doi: 10.1016/j.ymthe.2016.10.020. Epub 2017 Jan 4.
- Results publication: PubMed 28925994Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, Komanduri KV, Lin Y, Jain N, Daver N, Westin J, Gulbis AM, Loghin ME, de Groot JF, Adkins S, Davis SE, Rezvani K, Hwu P, Shpall EJ. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2018 Jan;15(1):47-62. doi: 10.1038/nrclinonc.2017.148. Epub 2017 Sep 19.
- Individual participant dataSharing planned: Undecided
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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.
Ming Zhou principal investigator
Hunan Provincial People's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TriCAR-T-CD19 in people with Non-hodgkin Lymphoma,B Cell, run by Timmune Biotech Inc. 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 13 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 6 Sep 2019. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Contact Ming Zhou (+86 0731 83928147, zhouming_0321@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (Incidence of treatment-related adverse events as assessed by CTCAE v4.0) (time frame: 30 Days). 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 NCT03497533, which also lists 3 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 6 Sep 2019.