A Prospective Clinical Study of BTK Inhibitor, PD-1 and Formustine in the First-line Treatment of Primary Central Nervous System Lymphoma

NCT04831658 | Unknown Phase 1

• 1 other identifier: hnslblzlzx20210303
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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).

Conditions

Primary Central Nervous System Lymphoma

Keywords

BTK inhibitor; PD-1; fotemustine; CRR; ORR; DCR; PFS; OS; ADR; Adverse events; ECOG score; laboratory examination; vital signs; physical examination; Time to disease progression (TTP); median survival (MST); quality of life (QOL); adverse reactions (ADR)

Outcome Measures

Primary Outcomes (10)

• DLT

  Dose-limiting toxicity

  up to 24 months

• AE

  adverse events

  up to 24 months

• ECOG performance score

  ECOG performance score

  up to 24 months

• laboratory tests

  laboratory tests

  up to 24 months

• vital signs

  vital signs

  up to 24 months

• physical examination

  physical examination

  up to 24 months

• ORR

  Objective Responder Rate

  up to 24 months

• DCR

  Disease Control Rate

  up to 24 months

• PFS

  Progression Free Survival

  up to 24 months

• OS

  Overall Survival

  up to 24 months

Secondary Outcomes (10)

• ORR

  up to 24 months

• DCR

  up to 24 months

• PFS

  up to 24 months

• OS

  up to 24 months

• ADR

  up to 24 months

Study Arms (1)

Orelabrutinib combined with PD-1 and fotemustine

EXPERIMENTAL

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)

Drug: the dose-escalation phase

Interventions

the dose-escalation phase DRUG

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.

Also known as: The extended treatment phase

Orelabrutinib combined with PD-1 and fotemustine

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mingzhi Zhang: lead

Study Sites (1)

Oncology Department of The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

RECRUITING

Related Publications (1)

• Zhao W, Li L, Fu X, Chang Y, Sun Z, Zhu L, Li X, Wang X, Yan J, Jia S, Ma S, Fan M, Qian S, Zhang Y, Yang Q, Qiao H, Chen Q, Zhang M, Zhang X. A first-line regimen combining Bruton's tyrosine kinase and programmed cell death protein-1 inhibitors with chemotherapy excluding methotrexate achieves high response rates in primary central nervous system lymphoma. Cancer. 2026 Jan 1;132(1):e70247. doi: 10.1002/cncr.70247.

  PMID: 41485126 DERIVED

MeSH Terms

Conditions

Myeloproliferative Syndrome, Transient

Study Officials

• Mingzhi zhang

  The First Affiliated Hospital of Zhengzhou University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mingzhi zhang, Pro.Dr.

CONTACT

13838565629; Mingzhi_zhang@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: the director of oncology department of the first affiliated hospital

Study Record Dates

• First Submitted: April 2, 2021
• First Posted: April 5, 2021
• Study Start: March 29, 2021
• Primary Completion: September 15, 2023
• Study Completion: September 15, 2024
• Last Updated: June 2, 2022

Record last verified: 2022-05

Locations

CN (1)