- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04831658
A Prospective Clinical Study of BTK Inhibitor, PD-1 and Formustine in the First-line Treatment of Primary Central Nervous System Lymphoma
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
Study Overview
Status
Conditions
Intervention / Treatment
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).
The extended treatment phase :
Primary study endpoints: objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) .
Secondary endpoints: time to disease progression (TTP), median survival (MST), adverse reactions (ADR), quality of life (QOL) .
The study adopts an open, one-arm, prospective clinical collaborative study . The initial treatment is BTK inhibitor (Obutinib), PD-1 monoclonal antibody combined with formustine :Orelabrutinib continues to be taken orally until the tumor is relieved for 3 months; PD-1 monoclonal antibody is used by intravenous drip, 21 days as a treatment cycle, and a total of 1 year of observation; formustine is used by intravenous drip for 21 days It is a treatment cycle, a total of 6 cycles of observation; after 2 cycles, the efficacy is evaluated, and adverse reactions are recorded. At the same time, MTX 12mg+Ara-C 50mg+Dex 5mg was injected into the CSF cytology-positive sheath, and intrathecal injection once per treatment cycle, a total of 6 times.
Second stage treatment :The efficacy was evaluated after 6 cycles of treatment in the initial stage. The CR patients continued to take orally abutinib (150mg, qd) for three months, and the PD-1 monoclonal antibody was used for maintenance treatment for up to 1 year; the PR patients received whole brain radiotherapy (WBRT), and at the same time Continue oral obritinib (150mg, qd) for three months and PD-1 monoclonal antibody maintenance treatment for up to one year; SD and PD patients choose methotrexate + pemetrexed combined chemotherapy for 4 cycles followed by whole brain radiotherapy (WBRT). WBRT: Regardless of age, supplementary WBRT 30-36Gy + partial reduction field irradiation up to 45Gy.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Henan
-
Zhengzhou, Henan, China, 450052
- Recruiting
- Oncology Department of The First Affiliated Hospital of Zhengzhou University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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)
|
The study adopts the "3+3" design,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.Orelabrutinib continues to be taken orally until the tumor is relieved for 3 months; PD-1 monoclonal antibody is used by intravenous drip, 21 days as a treatment cycle, and a total of 1 year of observation; formustine is used by intravenous drip for 21 days It is a treatment cycle, a total of 6 cycles of observation; after 2 cycles, the efficacy is evaluated, and adverse reactions are recorded.
At the same time, MTX 12mg+Ara-C 50mg+Dex 5mg was injected into the CSF cytology-positive sheath, and intrathecal injection once per treatment cycle, a total of 6 times.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
ORR
Time Frame: up to 24 months
|
Objective Responder Rate
|
up to 24 months
|
PFS
Time Frame: up to 24 months
|
Progression Free Survival
|
up to 24 months
|
OS
Time Frame: up to 24 months
|
Overall Survival
|
up to 24 months
|
DLT
Time Frame: up to 24 months
|
Dose-limiting toxicity
|
up to 24 months
|
AE
Time Frame: up to 24 months
|
adverse events
|
up to 24 months
|
ECOG performance score
Time Frame: up to 24 months
|
ECOG performance score
|
up to 24 months
|
laboratory tests
Time Frame: up to 24 months
|
laboratory tests
|
up to 24 months
|
vital signs
Time Frame: up to 24 months
|
vital signs
|
up to 24 months
|
physical examination
Time Frame: up to 24 months
|
physical examination
|
up to 24 months
|
DCR
Time Frame: up to 24 months
|
Disease Control Rate
|
up to 24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
ORR
Time Frame: up to 24 months
|
Objective Responder Rate
|
up to 24 months
|
PFS
Time Frame: up to 24 months
|
Progression Free Survival
|
up to 24 months
|
OS
Time Frame: up to 24 months
|
Overall Survival
|
up to 24 months
|
ADR
Time Frame: up to 24 months
|
Adverse Reaction Rate
|
up to 24 months
|
DCR
Time Frame: up to 24 months
|
Disease Control Rate
|
up to 24 months
|
CRR
Time Frame: up to 24 months
|
complete response rate
|
up to 24 months
|
TTP
Time Frame: up to 24 months
|
Time to disease progression
|
up to 24 months
|
MST
Time Frame: up to 24 months
|
median survival
|
up to 24 months
|
ADR
Time Frame: up to 24 months
|
adverse reactions
|
up to 24 months
|
QOL
Time Frame: up to 24 months
|
quality of life
|
up to 24 months
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- hnslblzlzx20210303
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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