Secondary Central Nervous System LymphomaPhase 2NCT05398224
R-MTX-zanbrutinib in Secondary CNS Lymphoma
A Phase 2 study testing Zanubrutinib, high-dose methotrexate (HD-MTX), rituximab in people with Secondary Central Nervous System Lymphoma, run by Peking University at 1 site in China.
Trial summary
Secondary central nervous system lymphoma (SCNSL) occurred in about 5% of patients with diffuse large B-cell lymphoma (DLBCL). The prognosis of SCNSL is very poor. A number of retrospective studies have shown that the median overall survival (mOS) since the diagnosis of CNSL is only 2.5-3.5 months, and the 2-year OS… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Secondary Central Nervous System Lymphoma
- What is being tested?
- Zanubrutinib, high-dose methotrexate (HD-MTX), rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteChina
- Study dates
- 26 Feb 2021to 26 May 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women ≥ 18, and ≤75 years of age
- Histologically documented systemic diffuse large B-cell lymphoma(DLBCL)
- Central nervous system (CNS) relapse (meningeal or /and intraparenchymal) with or without systemic lymphoma manifestations
- All patients need to have received at least one and ≤4 lines of prior therapy systemic lymphoma directed therapy.
- ECOG performance score 0-3
- Participants must have adequate bone marrow and organ function shown by:
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- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, Hemoglobin (Hgb) ≥ 9 g/dL, Platelets ≥ 75 x 109/L(≥ 50 x 109/L if bone marrow involvement)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal, total bilirubin ≤ 2 times the upper limit of normal
- International Normalized Ratio (INR) ≤ 1.5 and PTT (aPTT) ≤ 1.5 times the upper limit of normal
- serum creatinine (mg/dL)) ≤ 1.5 times the upper limit of normal ; calculated creatinine clearance(CrCl) ≥ 40ml/min using the Cockcroft-Gault equation
- Expected survival greater than 3 months
- Did not receive targeting agents within 10 days or receive chemortherapy, radiotherapy, or monoclonal antibody within 3 weeks
- Woman of reproductive potential must agree to use highly effective methods of birth control during the period of therapy and for 30 days after the last dose of the study drug. Men who are sexually active must agree to use highly effective contraception during the period of therapy and for 3 months after the last dose
- Ability of participants or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document
Who cannot join
- Newly diagnosed DLBCL with CNS involvement
- Previous treatment with Bruton's Tyrosine Kinase (BTK) inhibitors
- Received targeting agents within 10 days or received chemortherapy, radiotherapy, or monoclonal antibody within 3 weeks
- Patient has significant abnormalities on screening electrocardiogram (EKG) and active and significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, hypertension, valvular disease, pericarditis, or myocardial infarction within 6 months of screening
- History of severe bleeding diseases
- Patient is using warfarin or any other Coumadin-derivative anticoagulant or vitamin K antagonists. Patients must be off warfarin-derivative anticoagulants for at least seven days prior to starting the study drug. Low molecular weight heparin is allowed. Patients with congenital bleeding diathesis are excluded
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- Patient is taking a drug known to be a moderate and strong inhibitor or inducers of the P450 isoenzyme CYP3A. Participants must be off P450/CYP3A inhibitors and inducers for at least two weeks prior to starting the study drug
- Patient is known to have human immunodeficiency virus (HIV) infection
- Patient is known to have a history of active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) as determined by serologic tests
- Patient is known to have an uncontrolled active systemic infection
- Patients with serous cavity effustion
- Patient underwent major systemic surgery ≤ 4 weeks prior to starting the trial treatment or who has not recovered from the side effects of such surgery
- Women who are pregnant or nursing (lactating)
- The patient is unwell or unable to participate in all required study evaluations and procedures
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Peking University Cancer Hospital & Institute
Beijing, Beijing Municipality, 100142
Jun Zhu, zj@bjcancer.org
Yuqin Song, songyuqin622@sina.com
About this study
Official title: Phase II Study of Zanubrutinib in Combination With Rituximab and Methotrexate, Followed by Zanubrutinib Maintenance in Patients With Secondary Central Nervous System Lymphoma (SCNSL)
Secondary central nervous system lymphoma (SCNSL) occurred in about 5% of patients with diffuse large B-cell lymphoma (DLBCL). The prognosis of SCNSL is very poor. A number of retrospective studies have shown that the median overall survival (mOS) since the diagnosis of CNSL is only 2.5-3.5 months, and the 2-year OS rate is only 20%. At present, there is no consensus on the treatment of SCNSL, and new therapeutic strategies are urgently needed. Zanubrutinib is a new second-generation BTK inhibitor, which has showed good efficacy and safety in a variety of B-NHL. Zanubrutinib has showed good blood-brain barrier permeability in preclinical studies. This study attempts to evaluate the efficacy and safety of zanubrutinib combined with rituximab and high-dose methotrexate in the treatment of SCNSL in patients with DLBCL.
- Being tested
- Zanubrutinib, high-dose methotrexate (HD-MTX), rituximab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zanubrutinib, high-dose methotrexate (HD-MTX), rituximabDrug
Induction therapy: Zanubrutinib will be given as 160mg bid orally between days 1 and 14 of each 14-day cycle; rituximab will be given at 375mg/m2 intravenously on day 1 of each cycle; methotrexate at 3.5g/m2 for patients ≤65 or 1.5g/m2 for patients >65 (standard hydration/leucovorin support) will be given intravenously on day 2 of each 14-day cycle; for 6 cycles.
Consolidation therapy: For patients ≤65, autologous hematopoietic stem cell transplantation (ASCT with a conditioning regimen of thiotepa/carmustine) will be given as consolidation treatment after induction therapy.
Maintenance therapy:Drug: zanubrutinib. Zanubrutinib will be given as 160mg bid orally continuously until progression of the disease (PD), intolerable toxicity, death, or patient/investigator discretion.
| Study group | Role | What they receive |
|---|---|---|
| Experimental arm: Zanubrutinib, high-dose methotrexate (HD-MTX), rituximab | Experimental | Zanubrutinib in combination with rituximab and methotrexate, followed by zanubrutinib maintenance in patients with secondary central nervous system lymphoma (SCNSL) Receives: Drug: Zanubrutinib, high-dose methotrexate (HD-MTX), rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
progression free survival
Progression-free survival (PFS) is defined as the time from the date of treatment start to the date of the first documented PD or death due to any cause
Measured: 1-year
Secondary outcomes (5)
Overall response rate (ORR)
Measured: at the end of 6 cycles of induction therapy (each cycle is 14 days)
Complete response (CR)
Measured: at the end of 6 cycles of induction therapy
Partial response (PR)
Measured: at the end of 6 cycles of induction therapy (each cycle is 14 days)
Overall survival (OS)
Measured: 1-year
safety/tolerability by assessing the frequency and severity of adverse events
Measured: at the end of 6 cycles of induction therapy (each cycle is 14 days), 1 year and 2 year maintenance therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2022
- Study start26 Feb 2021
- Primary completion26 Feb 2024 (estimated)
- Study completion26 May 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Secondary Central Nervous System LymphomaStudies of the same condition, open and under way.
- More trials run by Peking UniversityThe 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
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jun Zhu, Peking University Cancer Hospital & Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05398224
- Sponsor's protocol ID
- 20210218
- Status last verified
- May 2022
- First submitted
- 22 May 2022
- Last updated
- 31 May 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Zanubrutinib in Combination With Rituximab and Methotrexate, Followed by Zanubrutinib Maintenance in Patients With Secondary Central Nervous System Lymphoma (SCNSL)
- ClinicalTrials.gov ID
- NCT05398224
- Acronym / sponsor ID
- 20210218
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Peking UniversityUniversity, hospital or other
- Study start
- 26 Feb 2021 (actual)
- Primary completion
- 26 Feb 2024 (estimated)
- Study completion
- 26 May 2024 (estimated)
- First posted
- 31 May 2022 (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.
Secondary central nervous system lymphoma (SCNSL) occurred in about 5% of patients with diffuse large B-cell lymphoma (DLBCL). The prognosis of SCNSL is very poor. A number of retrospective studies have shown that the median overall survival (mOS) since the diagnosis of CNSL is only 2.5-3.5 months, and the 2-year OS rate is only 20%. At present, there is no consensus on the treatment of SCNSL, and new therapeutic strategies are urgently needed. Zanubrutinib is a new second-generation BTK inhibitor, which has showed good efficacy and safety in a variety of B-NHL. Zanubrutinib has showed good blood-brain barrier permeability in preclinical studies. This study attempts to evaluate the efficacy and safety of zanubrutinib combined with rituximab and high-dose methotrexate in the treatment of SCNSL in patients with DLBCL.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental arm: Zanubrutinib, high-dose methotrexate (HD-MTX), rituximab | Experimental | Drug: Zanubrutinib, high-dose methotrexate (HD-MTX), rituximabZanubrutinib in combination with rituximab and methotrexate, followed by zanubrutinib maintenance in patients with secondary central nervous system lymphoma (SCNSL) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Men and women ≥ 18, and ≤75 years of age
- Histologically documented systemic diffuse large B-cell lymphoma(DLBCL)
- Central nervous system (CNS) relapse (meningeal or /and intraparenchymal) with or without systemic lymphoma manifestations
- All patients need to have received at least one and ≤4 lines of prior therapy systemic lymphoma directed therapy.
- ECOG performance score 0-3
Key exclusion criteria (14 listed)
- Newly diagnosed DLBCL with CNS involvement
- Previous treatment with Bruton's Tyrosine Kinase (BTK) inhibitors
- Received targeting agents within 10 days or received chemortherapy, radiotherapy, or monoclonal antibody within 3 weeks
- Patient has significant abnormalities on screening electrocardiogram (EKG) and active and significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, hypertension, valvular disease, pericarditis, or myocardial infarction within 6 months of screening
- History of severe bleeding diseases
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 |
|---|---|---|
| Zanubrutinib, high-dose methotrexate (HD-MTX), rituximabInduction therapy: Zanubrutinib will be given as 160mg bid orally between days 1 and 14 of each 14-day cycle; rituximab will be given at 375mg/m2 intravenously on day 1 of each cycle; methotrexate at 3.5g/m2 for patients ≤65 or 1.5g/m2 for patients >65 (standard hydration/leucovorin support) will be given intravenously on day 2 of each 14-day cycle; for 6 cycles. Consolidation therapy: For patients ≤65, autologous hematopoietic stem cell transplantation (ASCT with a conditioning regimen of thiotepa/carmustine) will be given as consolidation treatment after induction therapy. Maintenance therapy:Drug: zanubrutinib. Zanubrutinib will be given as 160mg bid orally continuously until progression of the disease (PD), intolerable toxicity, death, or patient/investigator discretion. | Drug | Experimental arm: Zanubrutinib, high-dose methotrexate (HD-MTX), rituximab |
Primary outcome
progression free survival
Time frame: 1-year
Progression-free survival (PFS) is defined as the time from the date of treatment start to the date of the first documented PD or death due to any cause
5 secondary outcomes
Overall response rate (ORR)
Time frame: at the end of 6 cycles of induction therapy (each cycle is 14 days)
Complete response (CR)
Time frame: at the end of 6 cycles of induction therapy
Partial response (PR)
Time frame: at the end of 6 cycles of induction therapy (each cycle is 14 days)
Overall survival (OS)
Time frame: 1-year
safety/tolerability by assessing the frequency and severity of adverse events
Time frame: at the end of 6 cycles of induction therapy (each cycle is 14 days), 1 year and 2 year maintenance therapy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2022.
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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 Zanubrutinib, high-dose methotrexate (HD-MTX), rituximab in people with Secondary Central Nervous System Lymphoma, run by Peking University 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 14 inclusion and 14 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 31 May 2022. 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 Lijuan Deng (0086-10-88196109, lijuan_deng@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
progression free survival (time frame: 1-year). 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 31 May 2022.