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RECRUITINGPHASE2

Orelabrutinib, Sintilimab and Temozolomide in Relapsed or Refractory Central Nervous System Lymphoma

A Phase II Study of Orelabrutinib, Sintilimab and Temozolomide in Treating Patients With Relapsed or Refractory Central Nervous System Lymphoma

NCT04961515•Second Affiliated Hospital, School of Medicine, Zhejiang University

View on ClinicalTrials.gov

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.

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.

Eligibility

Age

18 - 75 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Histologically documented primary central nervous system(CNS) lymphoma or secondary diffuse large B-cell lymphoma (DLBCL) isolated to CNS.
•2. Relapsed or refractory disease with at least 1 prior methotrexate-based therapy
•3. Participant must be able to understand and willing to sign a written informed consent document.
•4. 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.
•5. Participant must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study.
•6. Participant must be at least 18 years old on day of signing informed consent.
•7. PCNSL subjects should have evidence of measurable or evaluable enhancing disease on MRI
•8. 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.
•9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3.
•10. Life expectancy of \>3 months (in the opinion of the investigator)
+12 more criteria

Exclusion Criteria

•1. CNSL with systematic disease.
•2. The pathological diagnosis was T-cell lymphoma.
•3. 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.
•4. Prior allogenic stem cell transplant.
•5. Participation in another clinical study with an investigational product during the 4 weeks prior to the first day of study treatment.
•6. External beam radiation therapy to the CNS within 14 days of the first day of study treatment.
•7. 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.
•8. History of intracranial hemorrhage or clinically significant stroke within 6 months prior to first day of study treatment
•9. History of significant gastrointestinal disease that would limit absorption of oral medications.
•10. Active concurrent malignancy requiring active therapy.
+18 more criteria

Locations (1)

2nd Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, China

Key Dates

Start Date

July 1, 2021

Primary Completion Date

December 31, 2025

Completion Date

December 31, 2026

Last Updated

July 31, 2025

Enrollment

ESTIMATED participants

Conditions

Primary Central Nervous System Hodgkin Lymphoma

Interventions

Orelabrutinib

DRUG

Sintilimab

DRUG

Temozolomide (TMZ)

DRUG

Contacts

Wenbin Qian, Prof.

CONTACT

+8613605801032 qianwb@zju.edu.cn

Xianggui Yuan, Dr.

CONTACT

+8613989883884 yuanxg@zju.edu.cn

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: July 31, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

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