B-NHLPhase 2CART R/R NHLNCT06695013
Immunobridging/Maintenance Therapy Versus Non-bridging Therapy in CAR-T Therapy for Low-risk R/R B-NHL
A Phase 2 study testing zanubrutinib, CAR-T and Bridging radiotherapy in people with B-NHL and CART Therapy, run by Ruijin Hospital at 1 site in China.
Trial summary
This study aims to explore whether adding immunotherapy bridging treatment for low-risk refractory/relapsed B-NHL can demonstrate better outcomes, in order to find the most effective treatment plan for low-risk patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- B-NHL, CART Therapy
- What is being tested?
- zanubrutinib, CAR-T and Bridging radiotherapy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 144 participants
- Where
- 1 siteChina
- Study dates
- 20 Nov 2024to 20 Mar 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Age 18 or older, regardless of gender.
- Histologically confirmed B-cell non-Hodgkin lymphoma, according to Lugano diagnostic criteria.
- At least first-line treatment for relapsed or refractory patients, including chemotherapy regimens containing anthracyclines and anti-CD20 monoclonal antibody therapy; patients must meet definitions of refractory and recurrent.
- No prior CD19 CAR T cell therapy.
- Adequate organ function to assess tolerance to CAR-T therapy.
- Sufficient vascular access for leukapheresis.
- Ability to provide written informed consent and understand the study requirements and evaluation schedule.
- Fertile patients must agree to use highly effective contraception during the study and for 120 days post-treatment.
Who cannot join
- Patients with any of the following conditions will not be included in the study:
- History of allogeneic hematopoietic stem cell transplantation.
- History of epilepsy, cerebrovascular ischemia/bleeding, dementia, cerebellar disease, or any autoimmune disease involving the central nervous system.
- Any other malignancies within the past 2 years, except for cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors (Ta, Tis, and T1).
- Severe cardiovascular disease: NYHA grade II or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmias; NYHA grade III to IV heart failure or left ventricular ejection fraction (LVEF) < 50%.
- Allergy to any investigational drug or excipient.
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- Active viral hepatitis requiring treatment, including chronic HBV carriers with HBV DNA ≥ 500 IU/mL and positive HCV RNA.
- Active autoimmune disease or known history of allogeneic organ transplantation; long-term heavy use of immunosuppressants or other factors affecting study therapy.
- Active infection.
- History of uncontrolled systemic disease, such as diabetes or hypertension.
- Known HIV infection.
- Underlying medical condition or substance abuse that may interfere with drug administration or affect result interpretation, or increase treatment risk.
- End-organ damage from autoimmune disease within the past 2 years or systemic use of immunosuppressive drugs.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Immunobridging/Maintenance Therapy Versus Non-bridging Therapy in CAR-T Therapy for Low-risk Relapsed/Refractory B Cell Non-Hodgkin Lymphoma(R/R B-NHL): A Multicenter, Prospective, Randomized, Open-label, Controlled Clinical Study
This study aims to explore whether adding immunotherapy bridging treatment for low-risk refractory/relapsed B-NHL can demonstrate better outcomes, in order to find the most effective treatment plan for low-risk patients.
Read the detailed description
In the immunotherapy bridging treatment group, zanubrutinib ± radiotherapy will be used as the bridging treatment regimen, while those without bridging treatment will not receive bridging medications. Both groups will determine subsequent maintenance treatment based on efficacy at D28. Patients achieving complete response (CR) will not receive maintenance therapy, while those with partial response (PR) will be given oral zanubrutinib + PD-1 inhibitor for 2 years. Patients with stable disease (SD) or disease progression (PD) will not be included in this study.
- Conditions
- B-NHL, CART Therapy
- Being tested
- zanubrutinib, CAR-T, Bridging radiotherapy, Tislelizumab
- Keywords
- Zanubrutinib, maintenance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
zanubrutinibDrug
zanubrutinib 160 mg BID orally
CAR-TDrug
CAR-T Cell therapy
Bridging radiotherapyRadiation
For patients in the experimental group, the decision regarding radiotherapy will depend on whether the specific lesions are suitable.
TislelizumabDrug
200mg IV Q3-4W
| Study group | Role | What they receive |
|---|---|---|
| Immunotherapy bridging treatment | Experimental | Zanubrutinib ± radiotherapy was used as the bridging therapy in the immunobridging treatment group, a Follow-up maintenance treatment was determined according to the efficacy of D28 in the two groups. Patients with complete response (CR) were given no maintenance treatment, while patients with partial response (PR) were given Zanubrutinib orally plus PD-1 inhibitor for 2 years. Patients with stable SD or progressive PD were excluded from this study Receives: Drug: zanubrutinib; Drug: CAR-T; Radiation: Bridging radiotherapy; Drug: Tislelizumab |
| no bridging treatment | Active comparator | The control group will not receive bridging treatment. Maintenance treatment will be consistent with the experimental group. Receives: Drug: zanubrutinib; Drug: CAR-T; Drug: Tislelizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response rate(CRR) at 3-month
Complete response rate at 3-month is defined as the incidence of subjects achieving complete response (CR) at 3-month after CAR-T infusion according to the Lugano Classification, as determined by study investigators.
Measured: 3 months post CAR-T infusion
Secondary outcomes (7)
Complete response rate(CRR) on D28
CRR on D28 after infusion is defined as the incidence of subjects achieving complete response (CR) on day 28 after CAR-T infusion according to the Lugano Classification, as determined by study investigators.
Measured: 28 days post CAR-T infusion
Objective remission rate (ORR) on D28
Objective remission rate (ORR) on D28 is defined as the incidence of either a CR or a partial response (PR) on day 28 after CAR-T infusion per the Lugano Classification as determined by study investigators.
Measured: 28 days post CAR-T infusion
Objective remission rate (ORR) at 3-month
Objective remission rate (ORR) at 3-month is defined as the incidence of either a CR or a partial response (PR) at 3-month after CAR-T infusion per the Lugano Classification as determined by study investigators.
Measured: 3 months post CAR-T infusion
Progression-Free Survival (PFS)
PFS is defined as the time from the CAR-T infusion date to the date of disease progression or death from any cause.
Measured: 2 years post CAR-T infusion
Overall Survival (OS)
OS is defined as the time from CAR-T infusion to the date of death from any cause.
Measured: 2 years post CAR-T infusion
CAR-T cell expansion
CAR-T cell expansion is to evaluate the proliferation and persistence of CAR-T cells in the patient's body following infusion. It is measured through quantitative assays, such as flow cytometry or qPCR, to track CAR-T cell levels in peripheral blood at predefined intervals.
Measured: 2 years post CAR-T infusion
Adverse Events rate
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: 2 years post CAR-T infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2024
- Study start20 Nov 2024
- Primary completion20 Nov 2026 (estimated)
- Study completion20 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B-NHLStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 144 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
- NCT06695013
- Sponsor's protocol ID
- CLMB study
- Acronym
- CART R/R NHL
- Status last verified
- Jan 2025
- First submitted
- 31 Oct 2024
- Last updated
- 24 Jan 2025
- 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 24 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunobridging/Maintenance Therapy Versus Non-bridging Therapy in CAR-T Therapy for Low-risk Relapsed/Refractory B Cell Non-Hodgkin Lymphoma(R/R B-NHL): A Multicenter, Prospective, Randomized, Open-label, Controlled Clinical Study
- ClinicalTrials.gov ID
- NCT06695013
- Acronym / sponsor ID
- CART R/R NHL / CLMB study
- Conditions
- B-NHL, CART Therapy
- Keywords
- Zanubrutinib, maintenance
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 144 participants (estimated)
- Lead sponsor
- Ruijin HospitalUniversity, hospital or other
- Study start
- 20 Nov 2024 (actual)
- Primary completion
- 20 Nov 2026 (estimated)
- Study completion
- 20 Mar 2027 (estimated)
- First posted
- 19 Nov 2024 (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 study aims to explore whether adding immunotherapy bridging treatment for low-risk refractory/relapsed B-NHL can demonstrate better outcomes, in order to find the most effective treatment plan for low-risk patients.
Detailed description
In the immunotherapy bridging treatment group, zanubrutinib ± radiotherapy will be used as the bridging treatment regimen, while those without bridging treatment will not receive bridging medications. Both groups will determine subsequent maintenance treatment based on efficacy at D28. Patients achieving complete response (CR) will not receive maintenance therapy, while those with partial response (PR) will be given oral zanubrutinib + PD-1 inhibitor for 2 years. Patients with stable disease (SD) or disease progression (PD) will not be included in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Immunotherapy bridging treatment | Experimental | Drug: zanubrutinib, Drug: CAR-T, Radiation: Bridging radiotherapy, Drug: TislelizumabZanubrutinib ± radiotherapy was used as the bridging therapy in the immunobridging treatment group, a Follow-up maintenance treatment was determined according to the efficacy of D28 in the two groups. Patients with complete response (CR) were given no maintenance treatment, while patients with partial response (PR) were given Zanubrutinib orally plus PD-1 inhibitor for 2 years. Patients with stable SD or progressive PD were excluded from this study |
| no bridging treatment | Active comparator | Drug: zanubrutinib, Drug: CAR-T, Drug: TislelizumabThe control group will not receive bridging treatment. Maintenance treatment will be consistent with the experimental group. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age 18 or older, regardless of gender.
- Histologically confirmed B-cell non-Hodgkin lymphoma, according to Lugano diagnostic criteria.
- At least first-line treatment for relapsed or refractory patients, including chemotherapy regimens containing anthracyclines and anti-CD20 monoclonal antibody therapy; patients must meet definitions of refractory and recurrent.
- No prior CD19 CAR T cell therapy.
- Adequate organ function to assess tolerance to CAR-T therapy.
Key exclusion criteria (13 listed)
- History of allogeneic hematopoietic stem cell transplantation.
- History of epilepsy, cerebrovascular ischemia/bleeding, dementia, cerebellar disease, or any autoimmune disease involving the central nervous system.
- Any other malignancies within the past 2 years, except for cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors (Ta, Tis, and T1).
- Severe cardiovascular disease: NYHA grade II or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmias; NYHA grade III to IV heart failure or left ventricular ejection fraction (LVEF) < 50%.
- Allergy to any investigational 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 |
|---|---|---|
| zanubrutinibzanubrutinib 160 mg BID orally | Drug | Immunotherapy bridging treatment, no bridging treatment |
| CAR-TCAR-T Cell therapy | Drug | Immunotherapy bridging treatment, no bridging treatment |
| Bridging radiotherapyFor patients in the experimental group, the decision regarding radiotherapy will depend on whether the specific lesions are suitable. | Radiation | Immunotherapy bridging treatment |
| Tislelizumab200mg IV Q3-4W | Drug | Immunotherapy bridging treatment, no bridging treatment |
Primary outcome
Complete response rate(CRR) at 3-month
Time frame: 3 months post CAR-T infusion
Complete response rate at 3-month is defined as the incidence of subjects achieving complete response (CR) at 3-month after CAR-T infusion according to the Lugano Classification, as determined by study investigators.
7 secondary outcomes
Complete response rate(CRR) on D28
Time frame: 28 days post CAR-T infusion
Objective remission rate (ORR) on D28
Time frame: 28 days post CAR-T infusion
Objective remission rate (ORR) at 3-month
Time frame: 3 months post CAR-T infusion
Progression-Free Survival (PFS)
Time frame: 2 years post CAR-T infusion
Overall Survival (OS)
Time frame: 2 years post CAR-T infusion
CAR-T cell expansion
Time frame: 2 years post CAR-T infusion
Adverse Events rate
Time frame: 2 years post CAR-T infusion
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2025.
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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.
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 zanubrutinib, CAR-T and Bridging radiotherapy in people with B-NHL and CART Therapy, 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 13 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: looking for participants now, as of the sponsor's last update on 24 Jan 2025. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact zhao wei li, doctor Degree (+862164370045 ext. 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?
Complete response rate(CRR) at 3-month (time frame: 3 months post 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 24 Jan 2025.