Ignite Creation Date:
2024-05-06 @ 4:00 PM
Last Modification Date:
2024-10-26 @ 2:01 PM
Study NCT ID:
NCT04831658
Status:
UNKNOWN
Last Update Posted:
2022-06-02
First Post:
2021-04-02
Brief Title:
A Prospective Clinical Study of BTK Inhibitor PD-1 and Formustine in the First-line Treatment of Primary Central Nervous System Lymphoma
Sponsor:
Mingzhi Zhang
Organization:
Zhengzhou University
Study Overview
Official Title:
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
Status:
UNKNOWN
Status Verified Date:
2022-05
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 33 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 dataDLT 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 12mgAra-C 50mgDex 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
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 33 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 dataDLT 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 12mgAra-C 50mgDex 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None