Phase II Study of Orelabrutinib Combined With PD-1 Inhibitor in Relapsed/Refractory Primary Central Nervous System Lymphoma

NCT ID: NCT04899427

Last Updated: 2021-05-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-24
• Study Completion Date: 2023-10-24

Brief Summary

This is a prospective multicenter single-arm phase II study, and the purpose of this study is to evaluate the efficiency of Orelabrutinib combined with PD-1 inhibitor regimen relapsed/refractory primary intraocular lymphoma. Overall response rate （ORR） after 4 cycles is the primary endpoint.

Detailed Description

All the patients will be treated with Orelabrutinib combined with PD-1 inhibitor ：Orelabrutinib 150mg qd，Tislelizumab Injection 200mg d1 or Sintilimab injection 200mg d1， every 21-day for 1 cycle). Patients will be evaluated every 2 cycles by MRI scan during the first 6 cycles，and then the interval of investigation will be prolonged to 12 weeks. The patients who achieved complete remission (CR) or partial remission (PR) or stable disease (SD) will receive further treatment. The patients progressed disease (PD) will withdraw from the trial and receive salvage regimens. The treatment will be continued for 2 years or until progression of the disease (PD), unacceptable toxicity, or patient/investigator discretion.

During following-up, surveillance ophthalmologic examination and brain magnetic resonance imaging (MRI) scans can be performed every 3 months up for 2 years.

Conditions

Primary Central Nervous System Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

orelabrutinib combined with PD-1 inhibitor

The experimental arm will be treated orelabrutinib plus PD-1(programmed death）inhibitor every 21 days as one cycle. The responses will be evaluated every 2 cycles during the first 6 cycles and every 3 months until progression.

The investigators can choose Sintilimab Injection or Tislelizumab Injection at the beginning of treatment，but they can't exchange to another during the whole treatment.

Group Type: EXPERIMENTAL

orelabrutinib

Intervention Type: DRUG

Orelabrutinib will be given as 150mg per day orally, until progression of the disease (PD), unacceptable toxicity, or patient/investigator discretion.

Sintilimab

Intervention Type: DRUG

Sintilimab 200mg intravenous infusion d1, every 21 days for 1 cycle. The medicine will be given until progression of the disease (PD), unacceptable toxicity, or patient/investigator discretion.

Tislelizumab

Intervention Type: DRUG

Tislelizumab 200mg intravenous infusion d1, every 21 days for 1 cycle. The medicine will be given until progression of the disease (PD), unacceptable toxicity, or patient/investigator discretion.

Interventions

orelabrutinib

Orelabrutinib will be given as 150mg per day orally, until progression of the disease (PD), unacceptable toxicity, or patient/investigator discretion.

Intervention Type: DRUG

Sintilimab

Sintilimab 200mg intravenous infusion d1, every 21 days for 1 cycle. The medicine will be given until progression of the disease (PD), unacceptable toxicity, or patient/investigator discretion.

Intervention Type: DRUG

Tislelizumab

Tislelizumab 200mg intravenous infusion d1, every 21 days for 1 cycle. The medicine will be given until progression of the disease (PD), unacceptable toxicity, or patient/investigator discretion.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age ≥18 years old ≤75 Years old, male or female
• Primary Central nerves system lymphoma confirmed by cytology or histology according to WHO2016 criteria
• No evidence of systemic lymphoma
• Patients with a clear diagnosis of relapsed and/or refractory PCNSL: they received at least one regimen containing methotrexate.
• At least one measurable lesion according to Lugano 2014 criteria
• Adequate organ function and adequate bone marrow reserve

Exclusion Criteria

• Malignant tumors other than B-NHL within 5 years prior to screening, except cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and breast ductal carcinoma in situ after radical surgery
• Active HIV, HBV, HCV or treponema pallidum infection
• Any instability of systemic disease, including but not limited to active infection (except local infection), severe cardiac, liver, kidney, or metabolic disease need therapy
• Female subjects who have been pregnant or breastfeeding, or who plan to conceive during or within 1 year after treatment, or male subjects' partner plans to conceive within 1 year after their cell transfusion
• Active or uncontrolled infections requiring systemic treatment within 14 days before enrollment
• Any systemic antitumor therapy performed within 2 weeks before enrollment
• Previous use of other BTK inhibitors or PD-1 inhibitors.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Hospital

OTHER_GOV

Sponsor Role: collaborator

Beijing Tongren Hospital

OTHER

Sponsor Role: collaborator

Beijing Luhe Hospital

OTHER

Sponsor Role: collaborator

Shanxi Province Renmin Hospital

UNKNOWN

Sponsor Role: collaborator

Henan Cancer Hospital

OTHER_GOV

Sponsor Role: collaborator

Henan Province Renmin Hospital

UNKNOWN

Sponsor Role: collaborator

The Second Affiliated Hospital of Dalian Medical University

OTHER

Sponsor Role: collaborator

Hebei Medical University Fourth Hospital

OTHER

Sponsor Role: collaborator

The First Hospital of Chinese Medical University

UNKNOWN

Sponsor Role: collaborator

Qilu Hospital of Shandong University

OTHER

Sponsor Role: collaborator

The First Hospital of Zhengzhou University

UNKNOWN

Sponsor Role: collaborator

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Wei Zhang

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Facility Contacts

Wei Zhang

Role: primary

vv1223@vip.sina.com

13681473557

Other Identifiers

PUMCH-NHL-009

Identifier Type: -

Identifier Source: org_study_id