Non-Hodgkin LymphomaEarly Phase 1NCT03790891
Treatment of Non-Hodgkin Lymphoma With CD19-TriCAR-T/SILK Cell Therapy
A Early Phase 1 study testing CD19-TriCAR-T/SILK in people with Non-Hodgkin Lymphoma, run by Timmune Biotech Inc. at 3 sites in China.
Trial summary
This is a single arm, open-label, early phase Ⅰ study, to determine the safety and efficacy of CD19-TriCAR-T and CD19-TriCAR-SILK cell therapy in Non-Hodgkin lymphoma treatment. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Non-Hodgkin Lymphoma
- What is being tested?
- CD19-TriCAR-T/SILK
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 3 sitesChina
- Study dates
- 5 Jan 2019to 1 Jan 2022
- Phase
- Early 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 70 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;
- Refractory or relapsed malignant Non-Hodgkin lymphoma, defined as one or more of the following: Relapsed in 6 months after most recent therapy; Progressive disease in standard chemotherapy; Disease progression or relapsed in ≤12 months of ASCT;
- At least one measurable lesion per revised IWG Response Criteria;
- Aged <70 years;
- Expected survival ≥12 weeks; Eastern cooperative oncology group (ECOG) performance status of≤2;
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- 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 hardly to control（defined by investigator）;
- 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 or women of childbearing age who plan to conceive during the time period;
- 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 consider the patient may not be suitable for the study.
Trial locations and contacts
3 sites in 1 country.
China3 sites, 3 recruiting
- Recruiting
Hainan Cancer Hospital
Haikou, Hainan, 570100
Yuyang Tian, +86 18686853849, tianyuyang@163.com
- Recruiting
Hainan General Hospital
Haikou, Hainan, 570100
Yao Hongxia, +86 13876081106, yaohongxia768@163.com
Wu Yasong, +86 18020091931, yasong.wu@timmune.com
- Recruiting
The Second Affiliated Hospital of Hainan Medical University
Haikou, Hainan, 570100
Haifeng Lin, +86 13322060949, 13322060949@163.com
About this study
Official title: Adoptive Immunotherapy for Non-Hodgkin Lymphoma With CD19-TriCAR-T/SILK Cell
This is a single arm, open-label, early phase Ⅰ study, to determine the safety and efficacy of CD19-TriCAR-T and CD19-TriCAR-SILK cell therapy in Non-Hodgkin lymphoma treatment.
Read the detailed description
CD19-TriCAR contains an anti-CD19 scFv, a PD-L1 blocker, and a cytokine complex, enabling the CD19-TriCAR-T/SILK to simultaneously targeting the CD19 positive Non-Hodgkin lymphoma，blocking the inhibitory PD-L1 signal and stimulating innate T/NK cell activation and expansion, thus make it a tri-functional CAR (Tri-CAR). CD19-TriCAR-T is an autologous tri-functional CAR-T cell therapy, CD19-TriCAR-SILK is an Allogeneic tri-functional CAR-NK cell therapy, patients ineligible for leukapheresis or CAR-T therapy will be recommended for CD19-TriCAR-SILK therapy.
- Conditions
- Non-Hodgkin Lymphoma
- Being tested
- CD19-TriCAR-T/SILK
- Keywords
- CAR-T, TriCAR-T, CD19-TriCAR-T, CD19-TriCAR-SILK, Non-Hodgkin Lymphoma
- 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-T/SILKBiological
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide may be administered, followed by a single infusion of CD19-TriCAR-T cells or 4 repeat infusions of CD19-TriCAR-SILK cells.
| Study group | Role | What they receive |
|---|---|---|
| CD19-TriCAR-T/SILK | Experimental | CD19-TriCAR-T/SILK cells will be administered intravenously Receives: Biological: CD19-TriCAR-T/SILK |
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 posted2 Jan 2019
- Study start5 Jan 2019
- Primary completion1 Jun 2021 (estimated)
- Study completion1 Jan 2022 (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 LymphomaStudies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Timmune Biotech Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yao Hongxia, Principal investigator, Hainan General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03790891
- Sponsor's protocol ID
- 2018-127
- Status last verified
- Mar 2020
- First submitted
- 28 Dec 2018
- Last updated
- 13 Mar 2020
- 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 28925994Porter D, Frey N, Wood PA, Weng Y, Grupp SA. Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel. J Hematol Oncol. 2018 Mar 2;11(1):35. doi: 10.1186/s13045-018-0571-y.
PubMed 29499750
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adoptive Immunotherapy for Non-Hodgkin Lymphoma With CD19-TriCAR-T/SILK Cell
- ClinicalTrials.gov ID
- NCT03790891
- Acronym / sponsor ID
- 2018-127
- Conditions
- Non-Hodgkin Lymphoma
- Keywords
- CAR-T, TriCAR-T, CD19-TriCAR-T, CD19-TriCAR-SILK, Non-Hodgkin Lymphoma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Timmune Biotech Inc.Industry (pharma, biotech, devices)
- Study start
- 5 Jan 2019 (actual)
- Primary completion
- 1 Jun 2021 (estimated)
- Study completion
- 1 Jan 2022 (estimated)
- First posted
- 2 Jan 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 arm, open-label, early phase Ⅰ study, to determine the safety and efficacy of CD19-TriCAR-T and CD19-TriCAR-SILK cell therapy in Non-Hodgkin lymphoma treatment.
Detailed description
CD19-TriCAR contains an anti-CD19 scFv, a PD-L1 blocker, and a cytokine complex, enabling the CD19-TriCAR-T/SILK to simultaneously targeting the CD19 positive Non-Hodgkin lymphoma，blocking the inhibitory PD-L1 signal and stimulating innate T/NK cell activation and expansion, thus make it a tri-functional CAR (Tri-CAR). CD19-TriCAR-T is an autologous tri-functional CAR-T cell therapy, CD19-TriCAR-SILK is an Allogeneic tri-functional CAR-NK cell therapy, patients ineligible for leukapheresis or CAR-T therapy will be recommended for CD19-TriCAR-SILK therapy.
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/SILK | Experimental | Biological: CD19-TriCAR-T/SILKCD19-TriCAR-T/SILK cells will be administered intravenously |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 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;
- Refractory or relapsed malignant Non-Hodgkin lymphoma, defined as one or more of the following: Relapsed in 6 months after most recent therapy; Progressive disease in standard chemotherapy; Disease progression or relapsed in ≤12 months of ASCT;
- At least one measurable lesion per revised IWG Response Criteria;
- Aged <70 years;
Key exclusion criteria (9 listed)
- Presence of fungal, bacterial, viral, or other infection that is hardly to control（defined by investigator）;
- 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 or women of childbearing age who plan to conceive during the time period;
- 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-T/SILKA conditioning chemotherapy regimen of fludarabine and cyclophosphamide may be administered, followed by a single infusion of CD19-TriCAR-T cells or 4 repeat infusions of CD19-TriCAR-SILK cells. | Biological | CD19-TriCAR-T/SILK |
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 13 Mar 2020.
- 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 29499750Porter D, Frey N, Wood PA, Weng Y, Grupp SA. Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel. J Hematol Oncol. 2018 Mar 2;11(1):35. doi: 10.1186/s13045-018-0571-y.
- 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.
Yao Hongxia principal investigator
Hainan General Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing CD19-TriCAR-T/SILK in people with Non-Hodgkin Lymphoma, run by Timmune Biotech Inc. at 3 sites 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 9 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 13 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 Yao Hongxia (+86 13876081106, yaohongxia768@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 NCT03790891, 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 13 Mar 2020.