Sequential Treatment With RO-MTX After Pomalidomide, Orelabrutinib, Rituximab (POR) in Newly-diagnosed PCNSL

Primary Central Nervous System Lymphoma Clinical Trial

Official title:

Sequential Treatment Regimens With RO-MTX After Pomalidomide, Orelabrutinib, Rituximab (POR) as Frontline Therapy for Primary Central Nervous System Lymphoma: a Multicenter Prospective Single Arm Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05390749
• Other study ID #: PUMCH-NHL-013
• Status: Recruiting
• Phase: Phase 2
• Start date: April 11, 2022
• Est. completion date: April 1, 2026

Study information

• Verified date: April 2022
• Source: Peking Union Medical College Hospital
• Contact: Yan Zhang, M.D.
• Phone: +8613810000485
• Email: zhangyan10659[@]pumch.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter prospective single arm phase II study, and the purpose of this study is to evaluate the safety and efficacy of sequential treatment regimens with RO-MTX after pomalidomide, orelabrutinib, rituximab (POR) in newly-diagnosed primary central nervous system lymphoma, and explore the feasibility of chemo-free treatment in PCNSL. The primary objective was the overall response rate (ORR; defined as partial response [PR] or better) after 4 cycles of POR.

Description:

There are 2 sections of this trial. Step1: the patients will be treated with 4 cycles of POR regimen （Pomalidomide 4mg d1-d14, Orelabrutinib 150mg d1-d21, Rituximab 375mg/m2 d1, 21 days per cycle). The response will be evaluated every 2 cycles. The patients with PD will drop out of the study. Step2: Patients with CR/PR/SD after 4 cycles of POR treatment will be treated with 2 cycles of RO-MTX regimen（methotrexate 3.5g/m2 civ d1, Orelabrutinib 150mg d1-d21, Rituximab 375mg/m2 d1, 21 days per cycle). After 6 cycles of induction therapy, all patients were followed for survival data every 12 week until disease progression, disease recurrence, death, or study termination. Patients with progression were also followed up for survival data as above. Overall survival will be followed up to 3 years after the last subject entered the study. Establishing the feasibility of chemo-free treatment in primary central nervous system lymphoma will provide the foundation for a larger study of efficacy and long-term outcomes of chemo-free therapy for patients with PCNSL.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: April 1, 2026
• Est. primary completion date: April 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• • Newly diagnosed primary central nervous system lymphoma
• Pathological type is B cell lymphoma
• Age 18-70 years
• Demonstrate adequate marrow hemopoietic function as defined below:WBC>3.0×109/L,ANC>1.5×109/L,HGB>90g/L,PLT>80×109/L
• Demonstrate adequate organ function as defined below: cardiac function grade 0-2(NYHA);SpO2>88%( natural state);ALT<3UNL,TBil<2ULN; SCr>60ml/min/m2
• Having at least one measurable lesions
• Sign the Informed consent

Exclusion Criteria:

• • The pathological diagnosis was T-cell lymphoma.
• systemic lymphoma involved CNS
• Pre-existing uncontrolled active infection
• Acute myocardial infarction or unstable angina within 6 months; Uncontrolled hypertension and arrhythmia
• Active bleeding
• Allergic to any component of the investigational product.
• Subjects who are suspected to be unable to comply with the study protocol
• Pregnancy or active lactation

Related Conditions & MeSH terms

• Lymphoma
• Primary Central Nervous System Lymphoma

Intervention

Drug:
• Orelabrutinib
Orelabrutinib will be given as 150mg orally d1-d21 for 6 cycles,every 21 days for 1 cycle.
• Pomalidomide
Pomalidomide will be given as 4mg d1-d14 for 4 cycles,every 21 days for 1 cycle.
• Rituximab
Rituximab 375mg/m2 intravenous infusion d1, every 21 days for 1 cycle. 6 cycles will be prescribed as protocol
• Methotrexate
methotrexate 3.5g/m2 civ d1/cycle5-6

Locations

Country	Name	City	State
China	Beijing TianTan Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	Sanbo Brain Hospital Capital Medical University	Beijing	Beijing

Sponsors (3)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital	Beijing Tiantan Hospital, Sanbo Brain Hospital Capital Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overall response rate	ORR is defined as the proportion of patients with a best response of CR, CRu or PR	The ORR will be evaluated at 82 days from the POR treatment, which means after 4 cycles and each cycle is 21 days
Secondary	overall response rate	ORR is defined as the proportion of patients with a best response of CR, CRu or PR	The ORR will be evaluated at 126 days from date of signing the informed consent , which means after 6 cycles and each cycle is 21 days
Secondary	complete response rate	CR is defined as the proportion of patients with a best response of CR or CRu	The ORR will be evaluated at 82 days from the POR treatment, which means after 4 cycles and each cycle is 21 days
Secondary	2 years progression-free survival	2 years progression-free survival was calculated from the date of therapy until death from lymphoma or 2-year follow-up without relapsing	From date of signing the informed consent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Secondary	2 years overall survival	2 years progression-free survival was calculated from the date of therapy until death from lymphoma or 2-year follow-up alive	From date of signing the informed consent until the date of death from any cause, whichever came first, assessed up to 2 years
Secondary	The occurrence of adverse events and serious adverse events	Adverse events will be graded by the investigator according to the NCI-CTCAE Version 5.0.	during follow-up, up to 2 years