Primary Central Nervous System Hodgkin LymphomaPhase 2NCT04961515
Orelabrutinib, Sintilimab and Temozolomide in Relapsed or Refractory Central Nervous System Lymphoma
A Phase 2 study testing Orelabrutinib, Sintilimab and Temozolomide (TMZ) in people with Primary Central Nervous System Hodgkin Lymphoma, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial summary
This phase II trial is evaluating the efficacy and side effect of orelabrutinib, sintilimab and temozolomide as possible treatments for relapsed or refractory central nervous system lymphoma. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Primary Central Nervous System Hodgkin Lymphoma
- What is being tested?
- Orelabrutinib, Sintilimab and Temozolomide (TMZ)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2021to 31 Dec 2026
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically documented primary central nervous system(CNS) lymphoma or secondary diffuse large B-cell lymphoma (DLBCL) isolated to CNS.
- Relapsed or refractory disease with at least 1 prior methotrexate-based therapy
- Participant must be able to understand and willing to sign a written informed consent document.
- Participant must have signed and dated written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care.
- Participant must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study.
- Participant must be at least 18 years old on day of signing informed consent.
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- PCNSL subjects should have evidence of measurable or evaluable enhancing disease on MRI
- Able to submit at least 10 but up to 20 unstained formalin-fixed, paraffin-embedded (FFPE) slides from the initial or most recent tissue diagnosis for correlative studies. Histologically confirmed tissue will be required from the time of relapse or at the time of initial surgery. If tissue is unavailable and/or diagnosis was made from cerebrospinal fluid or vitreal biopsy, approval from the overall principal investigator is needed.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3.
- Life expectancy of >3 months (in the opinion of the investigator)
- Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1
- Must be able to tolerate lumbar puncture and MRI/CT.
- Demonstrate adequate organ function as defined below, all screening labs should be performed within 14 days of treatment initiation.
- Absolute neutrophil count (ANC) ≥ 1.0 x 109/L
- Platelets ≥ 75 x 10^9/L and no platelet transfusion within the past 7 days prior to initiation of protocol treatment
- Prothrombin time (PT), partial thromboplastin time (PTT), and international normalized ratio (INR) < 2 times the upper limit of normal
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal
- Serum bilirubin ≤ 1.5 times the upper limit of normal
- Creatinine clearance > 30 mL/min calculated by the Cockcroft-Gault formula using actual body weight
- Women of child-bearing potential, must agree to use a highly effective method of contraception consistently and correctly as described below during study treatment and for 120 days after study discontinuation.
- Male participants must agree to use at least one of the following methods of contraception starting with the first dose of study therapy through 120 days after the last dose of therapy:
- Ability to swallow oral medications.
Who cannot join
- CNSL with systematic disease.
- The pathological diagnosis was T-cell lymphoma.
- Prior chemotherapy within 4 weeks or prior targeted small molecule therapy within 2 weeks , prior antibody-drug-conjugates within 10weeks, autologous stem cell transplant within 6 months, prior to the first day of study treatment, prior to the first day of study treatment.
- Prior allogenic stem cell transplant.
- Participation in another clinical study with an investigational product during the 4 weeks prior to the first day of study treatment.
- External beam radiation therapy to the CNS within 14 days of the first day of study treatment.
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- Patient requires more than 8 mg of dexamethasone daily or the equivalent for control of CNS symptoms at the time of initiation of study therapy. Patients must taper off high dose corticosteroids for the control of CNS symptoms within 14 days after starting on study therapy.
- History of intracranial hemorrhage or clinically significant stroke within 6 months prior to first day of study treatment
- History of significant gastrointestinal disease that would limit absorption of oral medications.
- Active concurrent malignancy requiring active therapy.
- Prior therapy with a checkpoint inhibitor or BTK inhibitor.
- 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. Use of low molecular weight heparin and novel oral anticoagulants (eg. rivaroxaban, apixaban) is permitted if required.
- Concurrent use of a moderate or strong inhibitor or inducer of the P450 isoenzyme CYP3A. Participants must be off P450/CYP3A inhibitors and inducers prior to starting the study drug.
- Receipt of live attenuated vaccine within 30 days prior to the first day of study treatment. Note: Patients, if enrolled, should not receive live vaccine while receiving IP and up to 30 days after the last day of study treatment.
- Suspicion of or confirmed progressive multifocal leukoencephalopathy
- Active autoimmune disease (including autoimmune hemolytic anemia and immune thrombocytopenia purpura) requiring systemic treatment within the past two years (i.e. with the use of disease modifying agents, corticosteroids, or immunosuppressive drugs). The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (e.g., due to Hashimoto syndrome) stable on hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Patients without active disease in the last 5 years may be included but only after consultation with the study physician
- Patients with celiac disease controlled by diet alone
- Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroids replacement therapy for adrenal or pituitary insufficiency, etc.)
- Significant medical diseases or conditions, as assessed by the investigator, that would substantially increase the risk to benefit ratio of participating in the study. This includes, but is not limited to, acute myocardial infarction in the past 6 months, unstable angina, uncontrolled diabetes mellitus, significant active infections, severely immunocompromised state, and congestive heart failure, New York Heart Association Class III-IV.
- Known bleeding diathesis (e.g. von Willebrand's disease), hemophilia, or active bleeding.
- Known Human immunodeficiency virus (HIV) infection.
- Known active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) as determined by serologic tests and/or PCR.
- History of invasive fungal infection, including invasive aspergillosis, or known active tuberculosis.
- Major surgery ≤ 6 weeks prior to starting the trial treatment (or has not recovered from the side effects of such surgery) or plans to have surgery within 2 weeks of the first dose of the study drug.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
2nd Affiliated Hospital, School of Medicine, Zhejiang University
Hangzhou, Zhejiang, 310009
Xianggui Yuan, MD, PhD, +8613989883884, yuanxg@zju.edu.cn
Wenbin Qian, MD, PhD, +8613605801032, qianwb@zju.edu.cn
About this study
Official title: A Phase II Study of Orelabrutinib, Sintilimab and Temozolomide in Treating Patients With Relapsed or Refractory Central Nervous System Lymphoma
This phase II trial is evaluating the efficacy and side effect of orelabrutinib, sintilimab and temozolomide as possible treatments for relapsed or refractory central nervous system lymphoma.
Read the detailed description
Orelabrutinib and anti-PD-1 monoclonal antibodies represent promising therapeutic classes for central nervous system lymphoma (CNSL). Given the poor outcomes and limited treatment options for relapsed or refractory CNSL, this study aims to evaluate the efficacy and toxicity of orelabrutinib combined with temozolomide and sintilimab in this population.
Participants will receive fixed-dose orelabrutinib, sintilimab, and temozolomide for up to six 21-day cycles (induction phase), followed by sintilimab maintenance until disease progression (PD), intolerable toxicity, investigator/patient decision to withdraw, or a maximum treatment duration of 2 years (whichever occurs first). Tumor response will be assessed by MRI every two cycles during induction and every three months thereafter.
- Being tested
- Orelabrutinib, Sintilimab, Temozolomide (TMZ)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OrelabrutinibDrug
Orelabrutinib: 150 mg orally once daily
SintilimabDrug
Sintilimab: 200 mg intravenously every 3 weeks
Temozolomide (TMZ)Drug
Temozolomide: 150 mg/m² orally on days 1-5 of each 21-day cycle
| Study group | Role | What they receive |
|---|---|---|
| OST regimen | Experimental | Participants will receive:
1. Orelabrutinib: 150 mg orally once daily;
2. Sintilimab: 200 mg intravenously every 3 weeks;
3. Temozolomide: 150 mg/m² orally on days 1-5 of each 21-day cycle; Treatment consists of up to six 21-day cycles (induction phase), followed by sintilimab monotherapy maintenance until disease progression (PD), intolerable toxicity, investigator/patient decision to withdraw, or completion of 2 years total treatment (whichever occurs first). Tumor response will be assessed by MRI every two cycles during induction and quarterly thereafter Receives: Drug: Orelabrutinib; Drug: Sintilimab; Drug: Temozolomide (TMZ) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR)
The objective response rate (ORR) is defined as the proportion of patients with a best response of CR or PR
Measured: 2years
Secondary outcomes (3)
Progression-free survival (PFS)
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Measured: 2 years
Overall survival (OS)
OS is defined as the duration of time from start of treatment to time of death.
Measured: 2 years
Duration of response
The duration of overall response is measured from the time measurement
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2021
- Study start1 Jul 2021
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Central Nervous System Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 19 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Sir Run Run Shaw Hospital, First Affiliated Hospital of Zhejiang University, Wenzhou Central Hospital, Second Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Tongde Hospital, First People's Hospital of Hangzhou, Zhejiang Provincial People's Hospital, Jinhua Central Hospital, Jinhua People's Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Huzhou Central Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04961515
- Sponsor's protocol ID
- I2021001524
- Status last verified
- Jul 2025
- First submitted
- 15 Jun 2021
- Last updated
- 31 Jul 2025
- 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 31 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Orelabrutinib, Sintilimab and Temozolomide in Treating Patients With Relapsed or Refractory Central Nervous System Lymphoma
- ClinicalTrials.gov ID
- NCT04961515
- Acronym / sponsor ID
- I2021001524
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 19 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Collaborators
- Sir Run Run Shaw Hospital, First Affiliated Hospital of Zhejiang University, Wenzhou Central Hospital, Second Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Tongde Hospital, First People's Hospital of Hangzhou, Zhejiang Provincial People's Hospital, Jinhua Central Hospital, Jinhua People's Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Huzhou Central Hospital
- Study start
- 1 Jul 2021 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 14 Jul 2021 (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 phase II trial is evaluating the efficacy and side effect of orelabrutinib, sintilimab and temozolomide as possible treatments for relapsed or refractory central nervous system lymphoma.
Detailed description
Orelabrutinib and anti-PD-1 monoclonal antibodies represent promising therapeutic classes for central nervous system lymphoma (CNSL). Given the poor outcomes and limited treatment options for relapsed or refractory CNSL, this study aims to evaluate the efficacy and toxicity of orelabrutinib combined with temozolomide and sintilimab in this population.
Participants will receive fixed-dose orelabrutinib, sintilimab, and temozolomide for up to six 21-day cycles (induction phase), followed by sintilimab maintenance until disease progression (PD), intolerable toxicity, investigator/patient decision to withdraw, or a maximum treatment duration of 2 years (whichever occurs first). Tumor response will be assessed by MRI every two cycles during induction and every three months thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| OST regimen | Experimental | Drug: Orelabrutinib, Drug: Sintilimab, Drug: Temozolomide (TMZ)Participants will receive: 1. Orelabrutinib: 150 mg orally once daily; 2. Sintilimab: 200 mg intravenously every 3 weeks; 3. Temozolomide: 150 mg/m² orally on days 1-5 of each 21-day cycle; Treatment consists of up to six 21-day cycles (induction phase), followed by sintilimab monotherapy maintenance until disease progression (PD), intolerable toxicity, investigator/patient decision to withdraw, or completion of 2 years total treatment (whichever occurs first). Tumor response will be assessed by MRI every two cycles during induction and quarterly thereafter |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Histologically documented primary central nervous system(CNS) lymphoma or secondary diffuse large B-cell lymphoma (DLBCL) isolated to CNS.
- Relapsed or refractory disease with at least 1 prior methotrexate-based therapy
- Participant must be able to understand and willing to sign a written informed consent document.
- Participant must have signed and dated written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care.
- Participant must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study.
Key exclusion criteria (28 listed)
- CNSL with systematic disease.
- The pathological diagnosis was T-cell lymphoma.
- Prior chemotherapy within 4 weeks or prior targeted small molecule therapy within 2 weeks , prior antibody-drug-conjugates within 10weeks, autologous stem cell transplant within 6 months, prior to the first day of study treatment, prior to the first day of study treatment.
- Prior allogenic stem cell transplant.
- Participation in another clinical study with an investigational product during the 4 weeks prior to the first day of study treatment.
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 |
|---|---|---|
| OrelabrutinibOrelabrutinib: 150 mg orally once daily | Drug | OST regimen |
| SintilimabSintilimab: 200 mg intravenously every 3 weeks | Drug | OST regimen |
| Temozolomide (TMZ)Temozolomide: 150 mg/m² orally on days 1-5 of each 21-day cycle | Drug | OST regimen |
Primary outcome
Objective response rate (ORR)
Time frame: 2years
The objective response rate (ORR) is defined as the proportion of patients with a best response of CR or PR
3 secondary outcomes
Progression-free survival (PFS)
Time frame: 2 years
Overall survival (OS)
Time frame: 2 years
Duration of response
Time frame: 2 years
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 31 Jul 2025.
- 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.
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 Orelabrutinib, Sintilimab and Temozolomide (TMZ) in people with Primary Central Nervous System Hodgkin Lymphoma, run by Second Affiliated Hospital, Zhejiang University, School of Medicine 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 22 inclusion and 28 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 31 Jul 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 Wenbin Qian, Prof. (+8613605801032, qianwb@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (ORR) (time frame: 2years). 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 Jul 2025.