Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Primary Central Nervous System Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Thiotepa

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Orelabrutinib dose escalation will occur using a standard 3+3 dose-escalation approach to determined the maximum tolerated dose(MTD) of orelabrutinib dose in combined with thiotepa, beginning at dose level I (150 mg daily) and potentially escalating to dose level 2 (200mg) with rules for escalation and de-escalation. If the dose-limiting toxicity is not found, the dose of 200mg will be used for phase II trial (RP2D).

Orelabrutinib: 150mg or 200mg orally daily. Thiotepa: The dose of thiotepa is fixed as 30 mg/m2 intravenously every 3 weeks (maximum 6 cycle).

Participants will receive orelabrutinib and thiotepa at the pre-determined dosage level established in Phase 1b, until progression of the disease (PD), unacceptable toxicity, or patient/investigator discretion. The response will be evaluated every 2 cycles.

Orelabrutinib: RP2D (150 mg or 200 mg qd) Thiotepa:Sintilimab: The dose of thiotepa is fixed as 30 mg/m2 intravenously every 3 weeks (maximum 6 cycle).

Orelabrutinib

30 mg/m2 intravenously every 3 weeks (maximum 6 cycle)

Huiqiang Huang, Professor

Huiqiang Huang

The purpose of this study was to investigate the maximum tolerated dose and efficacy of Orelabrutinib combined with Thiotepa in refractory and relapsed primary central nervous system lymphoma (PCNSL).

Orelabrutinib in Combination With Thiotepa in Refractory and Relapsed Primary CNS Lymphoma

Safety and Efficacy of Orelabrutinib（O） in Combination With Thiotepa（T） in Refractory and Relapsed Primary CNS Lymphoma： A Single-arm, Multicenter Phase Ib/II Study（OT）

DNA from tumor tissue and CSF will be sequencing by next generation sequencing (NGS).Identify the PNCSL-related variants and gene expression alterations by NGS.

To determine the maximum tolerated dose (MTD)

The overall response rate (ORR) including complete response (CR), unconfirmed complete (CRu) and partial response (PR) according to the 2005 Response Criteria of the International Primary CNS Lymphoma Collaborative Group (IPCG)

The objective response rate (ORR) is defined as the proportion of patients with a best response of CR, CRu or PR

The complete response rate (ORR) is defined as the proportion of patients with a best response of CR or CRu

The duration of overall response is measured from the time measurement

The disease control rate (DCR) is defined as the proportion of patients with a best response of CR, CRu, PR or SD

The progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first

The overall survival (OS) is defined as the duration of time from start of treatment to time of death.

All subjects who received at least one dose of OT will be included in the safety analysis. Adverse events will be graded by the investigator according to the NCI-CTCAE Version 5.0.

Spots Global Cancer Trial Database for refractory and relapsed primary cns lymphoma