Clinical trial NCT04899427: Phase II Study of Orelabrutinib Combined With PD-1 Inhibitor in Relapsed/Refractory Primary Central Nervous System Lymphoma
Official title: Orelabrutinib Combined With PD-1 Inhibitor in Relapsed/Refractory Primary Central Nervous System Lymphoma: a Prospective Multi-center Phase II Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Primary Central Nervous System Lymphoma
Keywords: Primary Central Nervous System Lymphoma
orelabrutinib
PD-1 inhibitor
Overall response rate
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Hospital
name: Beijing Tongren Hospital
name: Beijing Luhe Hospital
name: Shanxi Province Renmin Hospital
name: Henan Cancer Hospital
name: Henan Province Renmin Hospital
name: The Second Affiliated Hospital of Dalian Medical University
name: Hebei Medical University Fourth Hospital
name: The First Hospital of Chinese Medical University
name: Qilu Hospital of Shandong University
name: The First Hospital of Zhengzhou University
First posted: 2021-05-24
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: overall response rate
timeFrame: 3 weeks after the end of 4 cycles of induction (each cycle is 21 days)
Secondary outcomes:
measure: 1 years progression-free survival
timeFrame: from the date of treatment to the subject finished his 1 years follow-up phase or the disease relapsed or the death due to lymphoma
Other outcomes:
Locations:
city: Beijing
country: China
facility: Wei Zhang
state: Beijing
Study officials:
References: