Primary Central Nervous System Lymphoma
Conditions
Keywords
Primary Central Nervous System Lymphoma, orelabrutinib, PD-1 inhibitor, Overall response rate
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.
Interventions
DRUGorelabrutinib
Orelabrutinib will be given as 150mg per day orally, until progression of the disease (PD), unacceptable toxicity, or patient/investigator discretion.
DRUGSintilimab
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.
DRUGTislelizumab
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.
Sponsors
Beijing Hospital
Beijing Tongren Hospital
Beijing Luhe Hospital
Shanxi Province Renmin Hospital
Henan Cancer Hospital
Henan Province Renmin Hospital
The Second Affiliated Hospital of Dalian Medical University
Hebei Medical University Fourth Hospital
The First Hospital of Chinese Medical University
Qilu Hospital of Shandong University
The First Hospital of Zhengzhou University
Peking Union Medical College Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| overall response rate | 3 weeks after the end of 4 cycles of induction (each cycle is 21 days) | ORR was calculated by the proportion of patients who achieved complete remission and partial remission. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1 years progression-free survival | 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 | 1 years progression-free survival was calculated from the date of therapy until death from lymphoma or 1-year follow up without relapsing |
Countries
China
Outcome results
None listed