Relapsed Non Hodgkin LymphomaPhase 1NCT03540303
Cytoplasmic Activated PD-1 CAR T Cells in Refractory/Relapsed B Cell Lymphoma
A Phase 1 study testing CAR19 T cells carrying cytoplasmic activated PD-1 in people with Relapsed Non Hodgkin Lymphoma, run by Henan Cancer Hospital at 1 site in China.
Trial summary
Evaluation of the safety and efficacy of CAR19 T cells carrying cytoplasmic activated PD1 in patients with refractory relapsed B-cell lymphoma Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Relapsed Non Hodgkin Lymphoma
- What is being tested?
- CAR19 T cells carrying cytoplasmic activated PD-1
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteChina
- Study dates
- 12 Apr 2018to 30 Apr 2020
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18-70 years old and the expected lifetime >3 months
- Refractory/relapsed CD19 positive B cell lymphoma by pathology
- ECOG score <2
- Measureable lesions according to RECIST 1.1
- Sufficient heart, liver, kidney and bone marrow function (heart: no heart disease or coronary heart disease, patient heart function NYHA grade 1-2; liver: TBIL ≤ 3ULN, AST ≤ 2.5ULN, ALT ≤ 2.5ULN; kidney: Cr≤ 1.25ULN; bone marrow: WBC ≥ 2.0 × 109/L, Hb ≥ 80 g/L, PLT ≥ 30 × 109/L)
- no serious allergies
Show all 11Show fewer
- No other serious diseases that conflict with this protocol (eg, autoimmune diseases, immunodeficiency, organ transplantation)
- No other history of malignancy
- No serious mental disorders
- Women of childbearing age must be negative for blood pregnancy test within 7 days and must take appropriated contraceptive measures during and 3 months after the study
- The patient himself agrees to participate in this clinical study and signed the "informed consent"
Who cannot join
- Lactating women
- Severe infectious or viral diseases (HIV positive, syphilis, etc.)
- Active hepatitis B or C viral hepatitis
- Patients who used high-dose glucocorticoids within 1 week
- Participation in other clinical studies in the past 3 months or having been treated with other gene products
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Henan Cancer Hospital
Zhengzhou, Henan, 450000
Quanli Gao, M.D, +86-15038171966, gaoquanli2015@126.com
Lu Han, M.D, +86-13838583031, luhan0377@163.com
About this study
Official title: Phase Ⅰ Study of CAR19 T Cells Carrying Cytoplasmic Activated PD-1 in the Treatment of Refractory/Relapsed B Cell Lymphoma
Evaluation of the safety and efficacy of CAR19 T cells carrying cytoplasmic activated PD1 in patients with refractory relapsed B-cell lymphoma
Read the detailed description
Although CAR19 T cell therapy brings hope, the patients with refractory/relapsed B-cell lymphoma is still a problem for the current treatment. There are still some patients with poor therapeutic efficacy, and the efficacy of CAR19-T cell therapy remains to be improved. Basic research shows that there is a synergistic effect between CAR-T cell therapy and anti-PD1 pathway, and it did have efficacy in clinic. However, the regimen of CAR19-T cells combined anti-PD1 inhibitors need to be combined with the application of anti-PD1 antibody and culture of CART cells during the treatment, there may be adverse events to PD1 antibodies. In this study, CAR19T cells carrying cytosolic activated PD1 possess the dual effects of CAR19T cells and anti-PD1 or anti-PD-L1 antibodies while overcoming the adverse events of anti-PD1 inhibitors, and might have better efficacy than conventional CAR19T cells plus anti-PD1 or anti-PD-L1 antibody treatment, with fewer side effects.
- Conditions
- Relapsed Non Hodgkin Lymphoma
- Being tested
- CAR19 T cells carrying cytoplasmic activated PD-1
- Keywords
- relapsed/refractory, B cell, lymphoma, CAR
- Medical subject headings
- Lymphoma, Non-Hodgkin, Recurrence, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAR19 T cells carrying cytoplasmic activated PD-1Drug
step 1: Collect 50-100ml of peripheral blood for culture of CAR19 T cells carrying cytoplasmic activated PD-1 step 2. After 72 hours, pretreated with FC regimen, details as follow Cyclophosphamide 600-800mg/m2 for 2 days Fludarabine 25-30mg/m2 for 3 days step 3: After another 48 hours transfusion the cells back to the patients the numbers of infused CAR T cells are 2x106 /kg for the first 3 patients, 6x106 /kg for the second 3 patients and 18x106 /kg for the third 3 patients.
After finishing this, another 6 patients will be enrolled for observation of efficacy.
| Study group | Role | What they receive |
|---|---|---|
| CAR19 T cells carrying cytoplasmic activated PD-1 | Experimental | patients with refractory/relapsed B-NHL receive a preconditioning before infusion of CAR T cells. Receives: Drug: CAR19 T cells carrying cytoplasmic activated PD-1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
safety: occurrence of study related adverse events
occurrence of study related adverse events
Measured: 6 months
Secondary outcomes (1)
objective response rate
tumor burdens shrink more than 30 percent by RECIST1.1
Measured: 3 months and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2018
- Study start12 Apr 2018
- Primary completion30 Apr 2020 (estimated)
- Study completion30 Apr 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed Non Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by Henan Cancer HospitalThe 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
- Intervention model
- Sequential
- Model description
- CAR19 T cell therapy improves the clinical efficacy of refractory/relapsed B-cell lymphoma, and the combined PDL1 inhibitors may further improve the efficacy of CD19 CART in the treatment of lymphomas. The clinical efficacy of KITE's CAR19 T cells and PD-L1 inhibition was reported. This phase 1 study was conducted in 9 patients with DLBCL, 8 patients got remission and during which 5 got complete remission. However, this type of treatment requires more data and observation in a larger sample of patients. In addition, Kite Pharmaceuticals' CD19 CART is priced at 370,000 US dollars. The cost of immune checkpoint inhibitors is also very expensive. Only very small proportion of patients could afford for that expenses. In this study, genetically engineered CAR T cells, which carry cytoplasmic activated PD1, are not inhibited by PDL1 molecules, will avoid the simultaneous application of immune checkpoint antibodies and the according adverse events.
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Henan Cancer Hospital
- Sponsor type
- Other government
- Collaborators
- The Pregene (ShenZhen) Biotechnology Company, Ltd.
- Responsible party
- Sponsor
- Investigators
- Yongping Song, M.D, Study chair, Henan Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03540303
- Sponsor's protocol ID
- HenanCH CAR 2-1
- Status last verified
- Apr 2018
- First submitted
- 16 May 2018
- Last updated
- 30 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ⅰ Study of CAR19 T Cells Carrying Cytoplasmic Activated PD-1 in the Treatment of Refractory/Relapsed B Cell Lymphoma
- ClinicalTrials.gov ID
- NCT03540303
- Acronym / sponsor ID
- HenanCH CAR 2-1
- Conditions
- Relapsed Non Hodgkin Lymphoma
- Keywords
- relapsed/refractory, B cell, lymphoma, CAR
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Henan Cancer HospitalOther government
- Collaborators
- The Pregene (ShenZhen) Biotechnology Company, Ltd.
- Study start
- 12 Apr 2018 (actual)
- Primary completion
- 30 Apr 2020 (estimated)
- Study completion
- 30 Apr 2020 (estimated)
- First posted
- 30 May 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.
Evaluation of the safety and efficacy of CAR19 T cells carrying cytoplasmic activated PD1 in patients with refractory relapsed B-cell lymphoma
Detailed description
Although CAR19 T cell therapy brings hope, the patients with refractory/relapsed B-cell lymphoma is still a problem for the current treatment. There are still some patients with poor therapeutic efficacy, and the efficacy of CAR19-T cell therapy remains to be improved. Basic research shows that there is a synergistic effect between CAR-T cell therapy and anti-PD1 pathway, and it did have efficacy in clinic. However, the regimen of CAR19-T cells combined anti-PD1 inhibitors need to be combined with the application of anti-PD1 antibody and culture of CART cells during the treatment, there may be adverse events to PD1 antibodies. In this study, CAR19T cells carrying cytosolic activated PD1 possess the dual effects of CAR19T cells and anti-PD1 or anti-PD-L1 antibodies while overcoming the adverse events of anti-PD1 inhibitors, and might have better efficacy than conventional CAR19T cells plus anti-PD1 or anti-PD-L1 antibody treatment, with fewer side effects.
Study design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- CAR19 T cell therapy improves the clinical efficacy of refractory/relapsed B-cell lymphoma, and the combined PDL1 inhibitors may further improve the efficacy of CD19 CART in the treatment of lymphomas. The clinical efficacy of KITE's CAR19 T cells and PD-L1 inhibition was reported. This phase 1 study was conducted in 9 patients with DLBCL, 8 patients got remission and during which 5 got complete remission. However, this type of treatment requires more data and observation in a larger sample of patients. In addition, Kite Pharmaceuticals' CD19 CART is priced at 370,000 US dollars. The cost of immune checkpoint inhibitors is also very expensive. Only very small proportion of patients could afford for that expenses. In this study, genetically engineered CAR T cells, which carry cytoplasmic activated PD1, are not inhibited by PDL1 molecules, will avoid the simultaneous application of immune checkpoint antibodies and the according adverse events.
| Arm | Type | Receives |
|---|---|---|
| CAR19 T cells carrying cytoplasmic activated PD-1 | Experimental | Drug: CAR19 T cells carrying cytoplasmic activated PD-1patients with refractory/relapsed B-NHL receive a preconditioning before infusion of CAR T cells. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 18-70 years old and the expected lifetime >3 months
- Refractory/relapsed CD19 positive B cell lymphoma by pathology
- ECOG score <2
- Measureable lesions according to RECIST 1.1
- Sufficient heart, liver, kidney and bone marrow function (heart: no heart disease or coronary heart disease, patient heart function NYHA grade 1-2; liver: TBIL ≤ 3ULN, AST ≤ 2.5ULN, ALT ≤ 2.5ULN; kidney: Cr≤ 1.25ULN; bone marrow: WBC ≥ 2.0 × 109/L, Hb ≥ 80 g/L, PLT ≥ 30 × 109/L)
Key exclusion criteria (5 listed)
- Lactating women
- Severe infectious or viral diseases (HIV positive, syphilis, etc.)
- Active hepatitis B or C viral hepatitis
- Patients who used high-dose glucocorticoids within 1 week
- Participation in other clinical studies in the past 3 months or having been treated with other gene products
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 |
|---|---|---|
| CAR19 T cells carrying cytoplasmic activated PD-1step 1: Collect 50-100ml of peripheral blood for culture of CAR19 T cells carrying cytoplasmic activated PD-1 step 2. After 72 hours, pretreated with FC regimen, details as follow Cyclophosphamide 600-800mg/m2 for 2 days Fludarabine 25-30mg/m2 for 3 days step 3: After another 48 hours transfusion the cells back to the patients the numbers of infused CAR T cells are 2x106 /kg for the first 3 patients, 6x106 /kg for the second 3 patients and 18x106 /kg for the third 3 patients. After finishing this, another 6 patients will be enrolled for observation of efficacy. | Drug | CAR19 T cells carrying cytoplasmic activated PD-1 |
Primary outcome
safety: occurrence of study related adverse events
Time frame: 6 months
occurrence of study related adverse events
1 secondary outcome
objective response rate
Time frame: 3 months and 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2018.
Related trials for Relapsed Non Hodgkin Lymphoma
Active, not recruitingObservational study
Multi-omics Profiling of Relapsed Extranodal Natural Killer (NK)/T-cell Lymphoma
Extranodal NK/T-cell Lymphoma, Nasal Type
Active, not recruitingEarly Phase 1
Iomab-ACT: A Pilot Study of 131-I Apamistamab Followed by CD19-Targeted CAR T-Cell Therapy for Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia or Diffuse Large B-Cell Lymphoma
B-ALL, DLBCL
Active, not recruitingPhase 2
Valemetostat Tosylate (DS-3201b), an Enhancer of Zeste Homolog (EZH) 1/2 Dual Inhibitor, for Relapsed/Refractory Peripheral T-Cell Lymphoma (VALENTINE-PTCL01)
Relapsed/Refractory Peripheral T-Cell Lymphoma, Adult T Cell Leukemia/Lymphoma
RecruitingPhase 2
Testing the Effectiveness of a Combination Targeted Therapy (ViPOR) for Patients With Relapsed and/or Refractory Aggressive B-cell Lymphoma
High Grade B-Cell Lymphoma With MYC and BCL6 Rearrangements, Recurrent Diffuse Large B-Cell Lymphoma
RecruitingPhase 1/2
Dose Escalation and Dose Expansion Study of MDX2003 in Patients With Different Types of Lymphoma
Lymphoma, Waldenström Macroglobulinemia (WM)
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.
Yongping Song, M.D study chair
Henan Cancer 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 study testing CAR19 T cells carrying cytoplasmic activated PD-1 in people with Relapsed Non Hodgkin Lymphoma, run by Henan Cancer Hospital 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 5 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 30 May 2018. 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 Yongping Song, M.D (+86-371-65587199, songyongping2018@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
safety: occurrence of study related adverse events (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 May 2018; AzTrials last refreshed its copy on 6 Nov 2026.