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

Sponsor

Peking Union Medical College Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04899427

Collaborator

Beijing Hospital (Other), Beijing Tongren Hospital (Other), Beijing Luhe Hospital (Other), Shanxi Province Renmin Hospital (Other), Henan Cancer Hospital (Other), Henan Province Renmin Hospital (Other), The Second Affiliated Hospital of Dalian Medical University (Other), The Forth Hospital of Hebei Medical University (Other), The First Hospital of Chinese Medical University (Other), Qilu Hospital of Shandong University (Other), The First Hospital of Zhengzhou University (Other)

Enrollment

Location

Arm

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Primary Central Nervous System Lymphoma	Drug: orelabrutinib Drug: Sintilimab Drug: Tislelizumab	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

32 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Orelabrutinib Combined With PD-1 Inhibitor in Relapsed/Refractory Primary Central Nervous System Lymphoma: a Prospective Multi-center Phase II Study

Actual Study Start Date :

Mar 24, 2021

Anticipated Primary Completion Date :

Mar 24, 2023

Anticipated Study Completion Date :

Oct 24, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: orelabrutinib Orelabrutinib will be given as 150mg per day orally, until progression of the disease (PD), unacceptable toxicity, or patient/investigator discretion. 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. 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.

Arm

Intervention/Treatment

Experimental: 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.

Drug: orelabrutinib

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

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.

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.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wei Zhang	Beijing	Beijing	China	100730

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Peking Union Medical College Hospital

ClinicalTrials.gov Identifier:

NCT04899427

Other Study ID Numbers:

PUMCH-NHL-009

First Posted:

May 24, 2021

Last Update Posted:

May 24, 2021

Last Verified:

May 1, 2021

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Peking Union Medical College Hospital

Primary Central Nervous System Lymphoma

orelabrutinib

PD-1 inhibitor

Overall response rate

Additional relevant MeSH terms:

Lymphoma

Study Results

No Results Posted as of May 24, 2021