A Prospective Clinical Study of a New Generation of BTK Inhibitors Combined With PD-1 and Formustine in the First-line Treatment of Primary Central Nervous System Lymphoma
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- DCR
Study Overview
Brief Summary
To observe the efficacy and safety of a new generation of BTK inhibitor Orelabrutinib combined with PD-1 and fotemustine in the treatment of patients with primary central nervous system lymphoma (PCNSL).
Detailed Description
This study includes a dose escalation phase and an extended treatment phase . The dose-escalation phase： Primary study endpoint: Safety endpoint: including dose-limiting toxicity (DLT), adverse events, ECOG performance score, laboratory tests, vital signs, physical examination .
Secondary research endpoints: effectiveness endpoints: including complete response rate (CRR), objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).
The study adopts the "3+3" design, that is, 3-6 subjects in each group complete the administration, and the dose group determined as the maximum tolerated dose (MTD) is included in the group of 6 subjects, totaling 9-18 example. The dose planned to be explored is the daily oral dose of the BTK inhibitor abutinib, which is 100 mg, 150 mg and 200 mg, respectively. The doses of other drugs in the plan will not be escalated.
After the last subject in each dose group completes the 28-day restricted toxicity (DLT) assessment window after the administration, the investigator can start the entry into the next dose group after evaluating and agreeing to enter the next dose group based on clinical safety data.DLT was defined as any grade 3 or higher nonhematologic toxicity, any grade 4 hematologic toxicity, grade 3 febrile neutropenia, and grade 3 thrombocytopenia with significant bleeding.
When 1 case of DLT occurs among 3 subjects in a certain dose group, 3 subjects need to be added to the same dose group (6 subjects in this dose group complete the DLT assessment): If the additional 3 subjects are tested If there is no DLT, continue the dose escalation; if 1 of the 3 increased subjects has DLT, stop the dose escalation; if the increased 3 subjects have >1 of the subjects DLT, the dose escalation is stopped, and the dose needs to be lowered to continue to enroll 3 subjects for DLT evaluation. If DLT occurs in 2 of the 3 or 6 subjects in the dose group, then the previous low dose is defined as the maximum tolerated dose (MTD).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 69 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age 18-69 years; KPS score ≥ 60 points or ECOG score ≤ 2 points; expected survival time of more than 3 months; PCNSL confirmed pathologically by tissue biopsy (limited to the brain, not accompanied by lymphoma in other parts of the body) , And histopathological type is diffuse large B-cell lymphoma; no chemotherapy contraindications (blood picture and physiological examination result time <7 days); at least one measurable lesion according to RECIST standards; no other serious diseases that conflict with this plan ; Follow-up is possible; other anti-tumor drugs are not used during this treatment period, and bisphosphonate anti-bone metastasis therapy and other symptomatic treatments can be applied; understand the situation of this study and sign the informed consent.
Exclusion Criteria
- •Those who are currently receiving other chemical, radiotherapy and targeted therapies (received chemotherapy within 3 weeks, received radiotherapy within 2 weeks, or have not recovered from the acute toxicity of any previous treatment); pregnant or lactating women; yes Any uncontrollable medical disease (including active infection, uncontrolled diabetes, severe heart, liver, kidney dysfunction, and interstitial pneumonia, etc.); those who are contraindicated with chemotherapy such as cachexia; have had other malignant tumors in the past Those who have uncontrolled infections; those who have a history of uncontrollable mental illness; those who are considered unsuitable to participate in this trial by the investigator.
Arms & Interventions
Orelabrutinib combined with PD-1 and fotemustine
To observe the efficacy and safety of a new generation of BTK inhibitor abutinib combined with PD-1 and formustine in the treatment of newly-treated patients with primary central nervous system lymphoma (PCNSL)
Intervention: the dose-escalation phase (Drug)
Outcomes
Primary Outcomes
DCR
Time Frame: up to 24 months
Disease Control Rate
vital signs
Time Frame: up to 24 months
vital signs
physical examination
Time Frame: up to 24 months
physical examination
AE
Time Frame: up to 24 months
adverse events
ECOG performance score
Time Frame: up to 24 months
ECOG performance score
OS
Time Frame: up to 24 months
Overall Survival
DLT
Time Frame: up to 24 months
Dose-limiting toxicity
ORR
Time Frame: up to 24 months
Objective Responder Rate
laboratory tests
Time Frame: up to 24 months
laboratory tests
PFS
Time Frame: up to 24 months
Progression Free Survival
Secondary Outcomes
- TTP(up to 24 months)
- MST(up to 24 months)
- ORR(up to 24 months)
- PFS(up to 24 months)
- ADR(up to 24 months)
- OS(up to 24 months)
- QOL(up to 24 months)
- DCR(up to 24 months)
- CRR(up to 24 months)
Investigators
Mingzhi Zhang
the director of oncology department of the first affiliated hospital
Zhengzhou University