Lymphoma, B-CellPhase 2NCT04163302
Safety and Efficiency Study of CD19-PD1-CART Cell in Relapsed/Refractory B Cell Lymphoma
A Phase 2 study testing CD19-PD1-CART Cell in people with Lymphoma, B-Cell, run by Chinese PLA General Hospital at 1 site in China.
Trial summary
This is a single center, non-randomized, open-label, phase 2 study to evaluate the efficacy and safety of CD19-PD1-CART cells therapy for patients with relapsed/refractory B Cell Lymphoma. Read more about this study
- Who is it for?
- Ages 14 to 80 years
- Conditions the study is for
- Lymphoma, B-Cell
- What is being tested?
- CD19-PD1-CART Cell
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 7 Jul 2019to 1 Jul 2022
- Phase
- Phase 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 14 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female, aged 14 to 80 years (including 14 and 80 years old).
- The diagnosis was Refractory/relapsed B-cell lymphoma.(Meeting 1 of the first 4 items plus item 5)
- A.Tumor shrinkage less than 50% or disease progression after 4 cycles of standard chemotherapy.
- B.Achieved CR after standard chemotherapy, but relapsed within 6 months.
- C.2 or more relapses after CR.
- D.Not suitable for HSCT, or relapse after HSCT.
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- E.Subjects must have received adequate treatment in the past and the predicted survival is more than three months.
- Patient or his or her legal guardian voluntarily participates in this stuy and signs an informed consent form.
- Flow cytometry or immunohistochemistry showed CD19 positive in tumor cells.
- No serious concomitant disease and major organ function is not serious abnormal.
- ECOG physical condition score 0-3 or KPS score > 80.
- the test meets the following indicators:
- A.ALT/AST < 2.5 times the upper limit of normal (ULN) and total bilirubin≤34.2μmol/L.
- B.Creatinine < 176.8 μmol/L.
- C.WBC≥2.5×109/L ,LY≥0.7×109/L,LY%≥15%.
- D.PT/INR < 1.7 or PT was extended by less than 4 seconds.
Who cannot join
- Women who are pregnant or breastfeeding.
- Patients whose tumor cell don't have positive CD19 antigen.
- Active hepatitis B or hepatitis C, HIV/AIDS infection, any uncontrolled active infection.
- Patients who are using steroid drugs throughout the body currently.
- Patients who have received any gene therapy in the past.
- Patients who are allergy to immunotherapy and related drugs.
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- Patients with heavy heart disease or poorly controlled high blood pressure.
- Patients who received chemotherapy or radiation 4 weeks before the study began.
- Patients who are participating in other clinical trials.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Hai Nan Hospital of Chinese PLA General Hospital
Sanya, Hainan, 572000
Wenshuai Zheng, 15701572628, 18766179210@163.com
Lixun Guan, 15692537637, 15210758157@126.com
About this study
This is a single center, non-randomized, open-label, phase 2 study to evaluate the efficacy and safety of CD19-PD1-CART cells therapy for patients with relapsed/refractory B Cell Lymphoma.
Read the detailed description
Lymphoma is a malignant tumor originating from lymph nodes or other lymphoid tissues. It can be divided into B cells, T cells, and NK cell lymphomas depending on the origin of different lymphocytes. Among them, B cell lymphoma accounts for about 90% of lymphoma.
Chimeric antigen receptor T (CART) cells is a promising treatment for lymphoma. T lymphocytes from patients are separated and engineered with CD19-CAR, to specifically recognize and eliminate CD19-positive tumor cells. At present, many CD19CART cells therapy studies are in the stage of clinical research and have achieved significant clinical effects.
Although there are some CD9CART cells clinical trials, the therapeutic effect on lymphoma is significantly lower than that of acute leukemia. One of the reasons is that lymphoma has the nature of solid tumors, whichi has a certain immunosuppressive microenvironment. The clinical trials of anti-PD-1 antibody drugs against lymphoma also show good therapeutic efficacy. Therefore, the combination of anti-PD-1 or PD-L1 antibody and CD19CART is one of the ways to improve the therapeutic effect of CART cells.
The investigators screened PD-1 mutants that have high bind with the PD-L1 ligand, and prepared CD19CART which secretes the mutant PD-1Fc fusion protein. Preclinical studies have shown that CD19CART cells secreting mutant PD-1Fc fusion protein have a superior killing effect to CD19CART cells which does not express PD-1 fusion protein.
The trial was conducted to explore the safety and efficacy of CD19-PD1-CART cells in Relapsed/Refractory B Cell Lymphoma.
- Conditions
- Lymphoma, B-Cell
- Being tested
- CD19-PD1-CART Cell
- Keywords
- Lymphoma, Chimeric antigen receptor T cell, Chimeric antigen receptor, Immunotherapy, PD-1, CD19
- Medical subject headings
- Lymphoma, B-Cell, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD19-PD1-CART CellBiological
This study was a single-center, open-label, single-arm, non-randomized clinical trial, which has 3 groups by infusion dose level. Firstly, each dose group has 3 patients. The pretreatment regimen of cyclophosphamide (25mg/m2 for 3 consecutive days) and fludarabine (10mg/kg for 3 consecutive days) was given before CART cells were reinfused. CART cells were reinfused on the third day after the pretreatment. If no serious side effects emerges in the group, then the next group uses the subsequent higher dose. If serious side effects emerges in a single patients in any dose level, 3 more patients will be enrolled to the same dose level. After 9 or more patients, the investigators select the safest dose and recruit more patients for CART test to explore its effectiveness.
| Study group | Role | What they receive |
|---|---|---|
| CD19+ Lymphoma | Experimental | This study is to evaluate the efficacy and safety of CD19-PD1-CART cells therapy for patients with Relapsed/Refractory B Cell Lymphoma. Receives: Biological: CD19-PD1-CART Cell |
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 (5)
Overall Remission Rate(ORR) of CD19-PD1-CART cells in Lymphoma
ORR will be assessed from the first CAR-T cell infusion to death or last follow-up
Measured: 3 years
Overall survival(OS) of CD19-PD1-CART cells in Lymphoma
OS will be assessed from the first CAR-T cell infusion to death or last follow-up
Measured: 3 years
Progress-free survival(PFS) of CD19-PD1-CART cells in Lymphoma
PFS will be assessed from the first CAR-T cell infusion to death or last follow-up
Measured: 3 years
Rate of CD19-PD1-CARTcells in peripheral blood cells
In vivo (peripheral blood) rate of CD19-PD1-CART cells were determined by means of flow cytometry.
Measured: 3 years
Quantity of CD19-PD1-CART cells copies in peripheral blood cells.
In vivo (peripheral blood) quantity of CD19-PD1-CART cells 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 posted14 Nov 2019
- Study start7 Jul 2019
- Primary completion1 Jul 2021 (estimated)
- Study completion1 Jul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lymphoma, B-CellStudies of the same condition, open and under way.
- More trials run by Chinese PLA General 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This study was a single-center, open-label, single-arm, non-randomized clinical trial, which was divided in 3 groups by different infusion dose level. Firstly, each dose group has 3 patients. The pretreatment regimen of cyclophosphamide (25mg/m2 for 3 consecutive days) and fludarabine (10mg/kg for 3 consecutive days) was given before CART cells were reinfused. CART cells were reinfused on the third day after the pretreatment. If no serious side effects emerges in the group, then the next group uses the subsequent higher dose. If serious side effects emerges in a single patients in any dose level, 3 more patients will be enrolled to the same dose level. After 9 or more patients, the investigators select the safest dose and recruit more patients for CART test to explore its effectiveness.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Quanshun Wang, Chinese PLA General Hospital
- Investigators
- Quanshun Wang, Study chair, Hainan General HospitalWengshuai Zheng, Study director, Hainan General HospitalLixun Guan, Principal investigator, Hainan General HospitalLu Wang, Principal investigator, Hainan General HospitalYuanyuan Xu, Principal investigator, Hainan General HospitalYalei Hu, Principal investigator, Hainan General HospitalZhengyang Gu, Principal investigator, Hainan General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04163302
- Sponsor's protocol ID
- HNYY-XYK-02
- Status last verified
- Nov 2019
- First submitted
- 12 Nov 2019
- Last updated
- 15 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficiency Study of CD19-PD1-CART Cell in Relapsed/Refractory B Cell Lymphoma
- ClinicalTrials.gov ID
- NCT04163302
- Acronym / sponsor ID
- HNYY-XYK-02
- Conditions
- Lymphoma, B-Cell
- Keywords
- Lymphoma, Chimeric antigen receptor T cell, Chimeric antigen receptor, Immunotherapy, PD-1, CD19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Study start
- 7 Jul 2019 (actual)
- Primary completion
- 1 Jul 2021 (estimated)
- Study completion
- 1 Jul 2022 (estimated)
- First posted
- 14 Nov 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, non-randomized, open-label, phase 2 study to evaluate the efficacy and safety of CD19-PD1-CART cells therapy for patients with relapsed/refractory B Cell Lymphoma.
Detailed description
Lymphoma is a malignant tumor originating from lymph nodes or other lymphoid tissues. It can be divided into B cells, T cells, and NK cell lymphomas depending on the origin of different lymphocytes. Among them, B cell lymphoma accounts for about 90% of lymphoma.
Chimeric antigen receptor T (CART) cells is a promising treatment for lymphoma. T lymphocytes from patients are separated and engineered with CD19-CAR, to specifically recognize and eliminate CD19-positive tumor cells. At present, many CD19CART cells therapy studies are in the stage of clinical research and have achieved significant clinical effects.
Although there are some CD9CART cells clinical trials, the therapeutic effect on lymphoma is significantly lower than that of acute leukemia. One of the reasons is that lymphoma has the nature of solid tumors, whichi has a certain immunosuppressive microenvironment. The clinical trials of anti-PD-1 antibody drugs against lymphoma also show good therapeutic efficacy. Therefore, the combination of anti-PD-1 or PD-L1 antibody and CD19CART is one of the ways to improve the therapeutic effect of CART cells.
The investigators screened PD-1 mutants that have high bind with the PD-L1 ligand, and prepared CD19CART which secretes the mutant PD-1Fc fusion protein. Preclinical studies have shown that CD19CART cells secreting mutant PD-1Fc fusion protein have a superior killing effect to CD19CART cells which does not express PD-1 fusion protein.
The trial was conducted to explore the safety and efficacy of CD19-PD1-CART cells in Relapsed/Refractory B Cell 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 clinical trial, which was divided in 3 groups by different infusion dose level. Firstly, each dose group has 3 patients. The pretreatment regimen of cyclophosphamide (25mg/m2 for 3 consecutive days) and fludarabine (10mg/kg for 3 consecutive days) was given before CART cells were reinfused. CART cells were reinfused on the third day after the pretreatment. If no serious side effects emerges in the group, then the next group uses the subsequent higher dose. If serious side effects emerges in a single patients in any dose level, 3 more patients will be enrolled to the same dose level. After 9 or more patients, the investigators select the safest dose and recruit more patients for CART test to explore its effectiveness.
| Arm | Type | Receives |
|---|---|---|
| CD19+ Lymphoma | Experimental | Biological: CD19-PD1-CART CellThis study is to evaluate the efficacy and safety of CD19-PD1-CART cells therapy for patients with Relapsed/Refractory B Cell Lymphoma. |
Who may qualify
- Ages
- 14 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (16 listed)
- Male or female, aged 14 to 80 years (including 14 and 80 years old).
- The diagnosis was Refractory/relapsed B-cell lymphoma.(Meeting 1 of the first 4 items plus item 5)
- A.Tumor shrinkage less than 50% or disease progression after 4 cycles of standard chemotherapy.
- B.Achieved CR after standard chemotherapy, but relapsed within 6 months.
- C.2 or more relapses after CR.
Key exclusion criteria (9 listed)
- Women who are pregnant or breastfeeding.
- Patients whose tumor cell don't have positive CD19 antigen.
- Active hepatitis B or hepatitis C, HIV/AIDS infection, any uncontrolled active infection.
- Patients who are using steroid drugs throughout the body currently.
- Patients who have received any gene therapy in the past.
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-PD1-CART CellThis study was a single-center, open-label, single-arm, non-randomized clinical trial, which has 3 groups by infusion dose level. Firstly, each dose group has 3 patients. The pretreatment regimen of cyclophosphamide (25mg/m2 for 3 consecutive days) and fludarabine (10mg/kg for 3 consecutive days) was given before CART cells were reinfused. CART cells were reinfused on the third day after the pretreatment. If no serious side effects emerges in the group, then the next group uses the subsequent higher dose. If serious side effects emerges in a single patients in any dose level, 3 more patients will be enrolled to the same dose level. After 9 or more patients, the investigators select the safest dose and recruit more patients for CART test to explore its effectiveness. | Biological | CD19+ Lymphoma |
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).
5 secondary outcomes
Overall Remission Rate(ORR) of CD19-PD1-CART cells in Lymphoma
Time frame: 3 years
Overall survival(OS) of CD19-PD1-CART cells in Lymphoma
Time frame: 3 years
Progress-free survival(PFS) of CD19-PD1-CART cells in Lymphoma
Time frame: 3 years
Rate of CD19-PD1-CARTcells in peripheral blood cells
Time frame: 3 years
Quantity of CD19-PD1-CART cells copies in 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 15 Nov 2019.
- 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.
Quanshun Wang study chair
Hainan General Hospital
Wengshuai Zheng study director
Hainan General Hospital
Lixun Guan principal investigator
Hainan General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CD19-PD1-CART Cell in people with Lymphoma, B-Cell, run by Chinese PLA General 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 16 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 15 Nov 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 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 Quanshun Wang (15692538521, wqs63@sohu.com), or a site near the patient. 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?
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 15 Nov 2019.