Non-hodgkin Lymphoma,B CellPhase 1NCT03720496
Treatment of Refractory/Relapsed Non-Hodgkin Lymphoma With CD19-TriCART Cell Therapy
A Phase 1 study testing CD19-TriCAR-T 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, phase Ⅰ study, to determine the safety and efficacy of CD19-TriCAR-T, an autologous tri-functional anti- CD19 chimeric antigen receptor (CAR)-positive T cell therapy, in Refractory/ Relapsed CD19 Positive Non-Hodgkin Lymphoma (NHL). Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Non-hodgkin Lymphoma,B Cell
- What is being tested?
- CD19-TriCAR-T
- 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
- 1 Nov 2018to 1 Dec 2021
- 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 69 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;
- At least one measurable lesion per revised IWG Response Criteria;
- Aged 18 to 69 years;
- Expected survival ≥12 weeks;
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- 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);
Who cannot join
- 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;
- Patients with symptomatic central nervous system metastasis, intracranial metastasis, and cancer cells found in cerebrospinal fluid are not recommended to participate in this study. Symptom free or post-treatment stable disease or disappearance of lesions should not be excluded. The specific selection is ultimately determined by the investigator;
- Lactating women;
- Active infection with hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive);
- Known history of infection with HIV;
- Subjects need systematic usage of corticosteroid;
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- Subjects need systematic usage of immunosuppressive drug;
- 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
The Second Affiliated Hospital of Hainan Medical University
Haikou, Hainan, 570100
Haifeng Lin, +86 13322060949, 13322060949@163.com
Yasong Wu, +86 18020091931, yasong.wu@timmune.com
About this study
Official title: Adoptive Immunotherapy for Refractory/Relapsed Non-Hodgkin Lymphoma With CD19-TriCART Cells
This is a single arm, open-label, phase Ⅰ study, to determine the safety and efficacy of CD19-TriCAR-T, an autologous tri-functional anti- CD19 chimeric antigen receptor (CAR)-positive T cell therapy, in Refractory/ Relapsed CD19 Positive 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 CD19-TriCAR-T to simultaneously targeting the CD19 positive NHL cells，blocking the inhibitory PD-L1 signal and stimulating T/NK cell activation and expansion.
- Conditions
- Non-hodgkin Lymphoma,B Cell
- Being tested
- CD19-TriCAR-T
- Keywords
- CAR-T, TriCAR-T, CD19-TriCAR-T, Non-hodgkin Lymphoma, NHL, CD19-CAR-T
- 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.
CD19-TriCAR-TBiological
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 0.1-1 x 10^6 CAR+ T cells/kg body weight.
| Study group | Role | What they receive |
|---|---|---|
| CD19-TriCAR-T | Experimental | Tri-functional anti-CD19 chimeric antigen receptor transduced autologous T cells will be administered intravenously Receives: Biological: CD19-TriCAR-T |
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 v4.03）
Incidence of treatment-related adverse events as assessed by CTCAE v4.03
Measured: 24 months
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: 24 months
Partial response rate [PR] （Partial response rate per the revised International Working Group (IWG) Response Criteria）
Partial response rate per the revised International Working Group (IWG) Response Criteria
Measured: 24 months
Duration of Response （The time from response to relapse or progression）
The time from response to relapse or progression
Measured: 24 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: 24 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 posted25 Oct 2018
- Study start1 Nov 2018
- Primary completion1 Jun 2021 (estimated)
- Study completion1 Dec 2021 (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
- 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)
- Responsible party
- Sponsor
- Investigators
- Haifeng Lin, Principal investigator, The Second Affiliated Hospital of Hainan Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03720496
- Sponsor's protocol ID
- T2018-8
- Status last verified
- Dec 2019
- First submitted
- 24 Oct 2018
- Last updated
- 9 Dec 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Locke 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 28925994Kalos 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 21832238
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adoptive Immunotherapy for Refractory/Relapsed Non-Hodgkin Lymphoma With CD19-TriCART Cells
- ClinicalTrials.gov ID
- NCT03720496
- Acronym / sponsor ID
- T2018-8
- Conditions
- Non-hodgkin Lymphoma,B Cell
- Keywords
- CAR-T, TriCAR-T, CD19-TriCAR-T, Non-hodgkin Lymphoma, NHL, CD19-CAR-T
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- Timmune Biotech Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Nov 2018 (actual)
- Primary completion
- 1 Jun 2021 (estimated)
- Study completion
- 1 Dec 2021 (estimated)
- First posted
- 25 Oct 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, phase Ⅰ study, to determine the safety and efficacy of CD19-TriCAR-T, an autologous tri-functional anti- CD19 chimeric antigen receptor (CAR)-positive T cell therapy, in Refractory/ Relapsed CD19 Positive 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 CD19-TriCAR-T to simultaneously targeting the CD19 positive NHL cells，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 |
|---|---|---|
| CD19-TriCAR-T | Experimental | Biological: CD19-TriCAR-TTri-functional anti-CD19 chimeric antigen receptor transduced autologous T cells will be administered intravenously |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 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;
- At least one measurable lesion per revised IWG Response Criteria;
- Aged 18 to 69 years;
Key exclusion criteria (9 listed)
- 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;
- Patients with symptomatic central nervous system metastasis, intracranial metastasis, and cancer cells found in cerebrospinal fluid are not recommended to participate in this study. Symptom free or post-treatment stable disease or disappearance of lesions should not be excluded. The specific selection is ultimately determined by the investigator;
- Lactating women;
- Active infection with hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive);
- Known history of infection with HIV;
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 |
|---|---|---|
| CD19-TriCAR-TA 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 0.1-1 x 10^6 CAR+ T cells/kg body weight. | Biological | CD19-TriCAR-T |
Primary outcome
safety （Incidence of treatment-related adverse events as assessed by CTCAE v4.03）
Time frame: 24 months
Incidence of treatment-related adverse events as assessed by CTCAE v4.03
5 secondary outcomes
Complete response rate[CR] (Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma)
Time frame: 24 months
Partial response rate [PR] （Partial response rate per the revised International Working Group (IWG) Response Criteria）
Time frame: 24 months
Duration of Response （The time from response to relapse or progression）
Time frame: 24 months
Progression Free Survival （The time from the first day of treatment to the date on which disease progresses）
Time frame: 24 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 9 Dec 2019.
- Background: 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.
- Background: 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.
- 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.
- Individual participant dataSharing planned: No
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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.
Haifeng Lin principal investigator
The Second Affiliated Hospital of Hainan Medical University
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 CD19-TriCAR-T 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 11 inclusion and 9 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 9 Dec 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 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?
Contact Haifeng Lin (+86 13322060949, 13322060949@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 v4.03） (time frame: 24 months). 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 NCT03720496, 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 9 Dec 2019.