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

NCT04961515 | Recruiting Phase 2

• 1 other identifier: I2021001524
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Primary Central Nervous System Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  The objective response rate (ORR) is defined as the proportion of patients with a best response of CR or PR

  2years

Secondary Outcomes (3)

• Progression-free survival (PFS)

  2 years

• Overall survival (OS)

  2 years

• Duration of response

  2 years

Other Outcomes (2)

• ctDNA mutation and mean ctDNA concentration in serum and cerebrospinal fluid

  Baseline, every two months for up to three years after treatment

• The levels of cytokine concentration in serum and cerebrospinal fluid

  Baseline, every two months for up to three years after treatment

Study Arms (1)

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

Drug: Orelabrutinib; Drug: Sintilimab; Drug: Temozolomide (TMZ)

Interventions

Orelabrutinib DRUG

Orelabrutinib: 150 mg orally once daily

OST regimen

Sintilimab DRUG

Sintilimab: 200 mg intravenously every 3 weeks

OST regimen

Temozolomide (TMZ) DRUG

Temozolomide: 150 mg/m² orally on days 1-5 of each 21-day cycle

OST regimen

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead
• Sir Run Run Shaw Hospital: collaborator
• First Affiliated Hospital of Zhejiang University: collaborator
• Wenzhou Central Hospital: collaborator
• Second Affiliated Hospital of Wenzhou Medical University: collaborator
• Zhejiang Provincial Tongde Hospital: collaborator
• First People's Hospital of Hangzhou: collaborator
• Zhejiang Provincial People's Hospital: collaborator
• Jinhua Central Hospital: collaborator
• Jinhua People's Hospital: collaborator
• Yinzhou Hospital Affiliated to Medical School of Ningbo University: collaborator
• Huzhou Central Hospital: collaborator

Study Sites (1)

2nd Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310009, China

RECRUITING

MeSH Terms

Interventions

orelabrutinib; sintilimab; Temozolomide

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Wenbin Qian, Prof.

CONTACT

+8613605801032; qianwb@zju.edu.cn

Xianggui Yuan, Dr.

CONTACT

+8613989883884; yuanxg@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2021
• First Posted: July 14, 2021
• Study Start: July 1, 2021
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: July 31, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)