Diffuse Large B Cell LymphomaPhase 2NCT05871684
A Combination Study of CAR-T Therapy in r/r B-NHL
A Phase 2 study testing BTK inhibitor and PD-1 inhibitor in people with Diffuse Large B Cell Lymphoma, run by Ruijin Hospital at 1 site in China.
Trial summary
In registry studies of CAR-T products that have been marketed globally, patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (r/r B-NHL) have been enrolled to receive CAR-T infusion in combination with tyrosine kinase inhibitors (BTKi) or immune checkpoint inhibitors (PD-1 or PD-L1 antibodies), with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B Cell Lymphoma
- What is being tested?
- BTK inhibitor and PD-1 inhibitor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteChina
- Study dates
- 10 Jun 2023to 30 Aug 2024
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed diagnosis of B-cell non-Hodgkin's lymphoma; and according to the 2014 Lugano diagnostic criteria.
- Patients who have relapsed or are refractory to at least prior first-line therapy, including anthracycline-containing chemotherapy regimens and anti-CD20 monoclonal antibody therapy; patients must meet the definitions of refractory and relapsed.
- No prior CD19 CAR-T cell therapy
- Adequate organ function to receive CAR-T cell therapy
- Vascular condition adequate to perform leukapheresis
- Able to provide written informed consent (ICF) and able to understand and agree to comply with the study requirements and assessment schedule
- Patients of childbearing potential must be willing to use highly effective contraception for the duration of the study, and for 120 days after the last dose of treatment.
- ECOG 0-2
Who cannot join
- History of allogeneic hematopoietic stem cell transplantation;
- History of epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease or any autoimmune disease involving the central nervous system;
- Presence or current concurrent other malignancies within the past 2 years, with the exception of cured cervical carcinoma in situ, non-melanoma skin cancer and superficial bladder tumors (Ta (non-invasive tumors), Tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane));
- Serious cardiovascular disease: grade II or higher myocardial ischemia or myocardial infarction, poorly controlled arrhythmias; grade III-IV cardiac insufficiency by NYHA criteria, or cardiac ultrasound suggestive of left ventricular ejection fraction (LVEF) <50%;
- Hypersensitivity to any study drug or excipient;
- Patients with active viral hepatitis requiring treatment as determined by the investigator: chronic hepatitis B virus carriers with HBV DNA ≥ 500 IU/mL (2500 copies/mL) (HBV DNA testing only for patients who test positive for hepatitis B surface antigen or core antibody); patients who test positive for HCV RNA (HCV testing only for patients who test positive for hepatitis C virus antibody) RNA testing);
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- Patients with any active autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enterocolitis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism), or a known history of allogeneic organ transplantation, or long-term heavy use of hormones or use of other immunomodulatory agents, or other patients assessed by the investigator as having implications for study treatment ;
- The presence of an active infection;
- History of uncontrollable systemic disease, including diabetes, hypertension, acute lung disease, etc;
- Known human immunodeficiency virus (HIV) infection;
- Presence of an underlying medical condition or alcohol/drug abuse or dependence that is detrimental to study drug administration, or that may affect interpretation of results, or that places the patient at high risk of developing treatment complications;
- Organ damage due to an autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) or the need for systemic application of immunosuppressive or other systemic disease-controlling drugs within the past 2 years.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai
Weili Zhao, zwl_trial@163.com
About this study
Official title: A Phase II Study of BTKi+Radiotherapy±Chemotherapy Bridging Before Chimeric Antigen Receptor T-cell Immunotherapy (CAR-T) in Combination With BTKi±PD-1 Inhibitor Maintenance Therapy for Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma (r/r B-NHL)
In registry studies of CAR-T products that have been marketed globally, patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (r/r B-NHL) have been enrolled to receive CAR-T infusion in combination with tyrosine kinase inhibitors (BTKi) or immune checkpoint inhibitors (PD-1 or PD-L1 antibodies), with objective remission rate (ORR) for CAR-T in combination with BTKi ranging from 83.3%-100% and complete remission rate (CRR) were 33.3-75%. The ORRs for objective remission rates for CAR-T combined with PD1/PD-L1 ranged from 50-91% and CRRs were 33.3-64%, respectively. With regard to safety, no dose-limiting toxic (DLT) occurred and the incidence of other adverse reactions was low, and studies demonstrated that BTKi or PD-1/PD-L1 antibodies could further enhance the responsiveness and durability of anti-CD19 CAR-T cell therapy. However, there are no studies exploring the efficacy and safety of clinical regimens using BTKi + radiotherapy ± chemotherapy as a bridging regimen to treat r/r B-NHL in combination with BTKi and/or PD-1 inhibitor after CAR-T cell infusion. In real-world applications of commercial CAR-T, CAR-T therapy combined with BTKi or PD-1/PD-L1 antibodies may further improve response rates and remission persistence in r/r B-NHL patients receiving CAR-T infusion back, with efficacy benefits while ensuring a manageable safety profile. Therefore, our center plans to conduct a phase II clinical study of Regent CAR-T 001(A phase II study of BTKi+radiotherapy±chemotherapy bridging before CAR-T cell therpay in combination with BTKi±PD-1 inhibitor for r/r B-NHL).
- Conditions
- Diffuse Large B Cell Lymphoma
- Being tested
- BTK inhibitor, PD-1 inhibitor
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BTK inhibitorDrug
Intervention were given during bridging therapy and maintanance treament of CAR-T cell therpay.
PD-1 inhibitorDrug
Intervention were given during maintanance treament of CAR-T cell therpay.
| Study group | Role | What they receive |
|---|---|---|
| The combination treatment group of CAR-T therapy | Experimental | Patients dicided to receive CAR-T cell therapy will be divided into groups A and B according to their tumor burden. Group A was given a bridging regimen of BTKi (160 mg b.i.d. p.o.) + radiotherapy + chemotherapy, and group B was given a bridging regimen of BTKi (160 mg b.i.d. p.o.) + radiotherapy; BTKi (160 mg b.i.d. p.o.) was given continuously from D1 to D28 after the return of CAR-T after infusion; Based on the results of the first evaluation on day 28 after CAR-T cell infusion, CR patients were divided into groups A1 and B1, and both groups were given BTKi (160 mg b.i.d. p.o.) for 3 months maintenance; PR patients were divided into groups A2 and B2, and both groups were given BTKi (160 mg b.i.d. p.o.) for 3 months maintenance and PD-1 inhibitor (200mg q3w i.v.) for 2 years maintenance; Receives: Drug: BTK inhibitor; Drug: PD-1 inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
3-month complete response rate
Percentage of participants with complete response at 3-months after CAR-T infusion determined on the basis of investigator assessments according to 2014 Lugano criteria.
Measured: 3-months after CAR-T infusion
Secondary outcomes (9)
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Measured: End of treatment visit (2 years after CAR-T cell infusion)
1-month objective response rate
Percentage of participants with response at 1-month after CAR-T infusion determined on the basis of investigator assessments according to 2014 Lugano criteria.
Measured: 1 month after CAR-T infusion
Progression-free survival
Progression-free survival was defined as the time from the date of leukapheresis until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria, or death from any cause, whichever occurred first.
Measured: End of treatment visit (2 years after CAR-T cell infusion)
Overall survival
Overall survival was defined as the time from the date of leukapheresis to the date of death from any cause.
Measured: End of treatment visit (2 years after CAR-T cell infusion)
Time to reponse
Time from CAR-T cell infusion to the first assessment of CR or PR on the basis of investigator assessments according to 2014 Lugano criteria.
Measured: End of treatment visit (2 years after CAR-T cell infusion)
Duration of response
Time from the first efficacy assessment of CR or PR to the time of first disease progression on the basis of investigator assessments according to 2014 Lugano criteria.
Measured: End of treatment visit (2 years after CAR-T cell infusion)
Peak Plasma Concentration (Cmax)
Detection of maximum amount of CAR-T cell expansion in patients.
Measured: End of treatment visit (2 years after CAR-T cell infusion)
Area under the plasma concentration versus time curve (AUC)
The area under the CAR-T concentration curve in 28 days after infusion.
Measured: 28 days after infusion
Time to Peak Plasma Concentration (Tmax)
The time to reach the highest CAR-T concentration
Measured: End of treatment visit (2 years after CAR-T cell infusion)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2023
- Study start10 Jun 2023
- Primary completion20 May 2024 (estimated)
- Study completion30 Aug 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Large B Cell LymphomaStudies of the same condition, open and under way.
- More trials run by Ruijin 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
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ruijin Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhao Weili, Ruijin Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05871684
- Sponsor's protocol ID
- CAR-T 001
- Status last verified
- Jul 2023
- First submitted
- 9 May 2023
- Last updated
- 1 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- 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 1 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of BTKi+Radiotherapy±Chemotherapy Bridging Before Chimeric Antigen Receptor T-cell Immunotherapy (CAR-T) in Combination With BTKi±PD-1 Inhibitor Maintenance Therapy for Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma (r/r B-NHL)
- ClinicalTrials.gov ID
- NCT05871684
- Acronym / sponsor ID
- CAR-T 001
- Conditions
- Diffuse Large B Cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Ruijin HospitalUniversity, hospital or other
- Study start
- 10 Jun 2023 (actual)
- Primary completion
- 20 May 2024 (estimated)
- Study completion
- 30 Aug 2024 (estimated)
- First posted
- 23 May 2023 (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.
In registry studies of CAR-T products that have been marketed globally, patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (r/r B-NHL) have been enrolled to receive CAR-T infusion in combination with tyrosine kinase inhibitors (BTKi) or immune checkpoint inhibitors (PD-1 or PD-L1 antibodies), with objective remission rate (ORR) for CAR-T in combination with BTKi ranging from 83.3%-100% and complete remission rate (CRR) were 33.3-75%. The ORRs for objective remission rates for CAR-T combined with PD1/PD-L1 ranged from 50-91% and CRRs were 33.3-64%, respectively. With regard to safety, no dose-limiting toxic (DLT) occurred and the incidence of other adverse reactions was low, and studies demonstrated that BTKi or PD-1/PD-L1 antibodies could further enhance the responsiveness and durability of anti-CD19 CAR-T cell therapy. However, there are no studies exploring the efficacy and safety of clinical regimens using BTKi + radiotherapy ± chemotherapy as a bridging regimen to treat r/r B-NHL in combination with BTKi and/or PD-1 inhibitor after CAR-T cell infusion. In real-world applications of commercial CAR-T, CAR-T therapy combined with BTKi or PD-1/PD-L1 antibodies may further improve response rates and remission persistence in r/r B-NHL patients receiving CAR-T infusion back, with efficacy benefits while ensuring a manageable safety profile. Therefore, our center plans to conduct a phase II clinical study of Regent CAR-T 001(A phase II study of BTKi+radiotherapy±chemotherapy bridging before CAR-T cell therpay in combination with BTKi±PD-1 inhibitor for r/r B-NHL).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| The combination treatment group of CAR-T therapy | Experimental | Drug: BTK inhibitor, Drug: PD-1 inhibitorPatients dicided to receive CAR-T cell therapy will be divided into groups A and B according to their tumor burden. Group A was given a bridging regimen of BTKi (160 mg b.i.d. p.o.) + radiotherapy + chemotherapy, and group B was given a bridging regimen of BTKi (160 mg b.i.d. p.o.) + radiotherapy; BTKi (160 mg b.i.d. p.o.) was given continuously from D1 to D28 after the return of CAR-T after infusion; Based on the results of the first evaluation on day 28 after CAR-T cell infusion, CR patients were divided into groups A1 and B1, and both groups were given BTKi (160 mg b.i.d. p.o.) for 3 months maintenance; PR patients were divided into groups A2 and B2, and both groups were given BTKi (160 mg b.i.d. p.o.) for 3 months maintenance and PD-1 inhibitor (200mg q3w i.v.) for 2 years maintenance; |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Histologically confirmed diagnosis of B-cell non-Hodgkin's lymphoma; and according to the 2014 Lugano diagnostic criteria.
- Patients who have relapsed or are refractory to at least prior first-line therapy, including anthracycline-containing chemotherapy regimens and anti-CD20 monoclonal antibody therapy; patients must meet the definitions of refractory and relapsed.
- No prior CD19 CAR-T cell therapy
- Adequate organ function to receive CAR-T cell therapy
- Vascular condition adequate to perform leukapheresis
Key exclusion criteria (12 listed)
- History of allogeneic hematopoietic stem cell transplantation;
- History of epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease or any autoimmune disease involving the central nervous system;
- Presence or current concurrent other malignancies within the past 2 years, with the exception of cured cervical carcinoma in situ, non-melanoma skin cancer and superficial bladder tumors (Ta (non-invasive tumors), Tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane));
- Serious cardiovascular disease: grade II or higher myocardial ischemia or myocardial infarction, poorly controlled arrhythmias; grade III-IV cardiac insufficiency by NYHA criteria, or cardiac ultrasound suggestive of left ventricular ejection fraction (LVEF) <50%;
- Hypersensitivity to any study drug or excipient;
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 |
|---|---|---|
| BTK inhibitorIntervention were given during bridging therapy and maintanance treament of CAR-T cell therpay. | Drug | The combination treatment group of CAR-T therapy |
| PD-1 inhibitorIntervention were given during maintanance treament of CAR-T cell therpay. | Drug | The combination treatment group of CAR-T therapy |
Primary outcome
3-month complete response rate
Time frame: 3-months after CAR-T infusion
Percentage of participants with complete response at 3-months after CAR-T infusion determined on the basis of investigator assessments according to 2014 Lugano criteria.
9 secondary outcomes
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0
Time frame: End of treatment visit (2 years after CAR-T cell infusion)
1-month objective response rate
Time frame: 1 month after CAR-T infusion
Progression-free survival
Time frame: End of treatment visit (2 years after CAR-T cell infusion)
Overall survival
Time frame: End of treatment visit (2 years after CAR-T cell infusion)
Time to reponse
Time frame: End of treatment visit (2 years after CAR-T cell infusion)
Duration of response
Time frame: End of treatment visit (2 years after CAR-T cell infusion)
Peak Plasma Concentration (Cmax)
Time frame: End of treatment visit (2 years after CAR-T cell infusion)
Area under the plasma concentration versus time curve (AUC)
Time frame: 28 days after infusion
Time to Peak Plasma Concentration (Tmax)
Time frame: End of treatment visit (2 years after CAR-T cell infusion)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2023.
- 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.
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 BTK inhibitor and PD-1 inhibitor in people with Diffuse Large B Cell Lymphoma, run by Ruijin 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 8 inclusion and 12 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 1 Aug 2023. 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 Weili Zhao, Doctor (+862164370045 ext. 610707, zwl_trial@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
3-month complete response rate (time frame: 3-months after CAR-T infusion). 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 1 Aug 2023.