Clinical trial NCT05390749: Sequential Treatment With RO-MTX After Pomalidomide, Orelabrutinib, Rituximab (POR) in Newly-diagnosed PCNSL
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Primary Central Nervous System Lymphoma
Keywords: Orelabrutinib
Pomalidomide
Rituximab
primary central nervous system lymphoma
methotrexate
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Tiantan Hospital
name: Capital Medical University
First posted: 2022-05-25
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: overall response rate
timeFrame: The ORR will be evaluated at 82 days from the POR treatment, which means after 4 cycles and each cycle is 21 days
Secondary outcomes:
measure: overall response rate
timeFrame: 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
measure: complete response rate
timeFrame: The ORR will be evaluated at 82 days from the POR treatment, which means after 4 cycles and each cycle is 21 days
measure: 2 years progression-free survival
timeFrame: 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
measure: 2 years overall survival
timeFrame: From date of signing the informed consent until the date of death from any cause, whichever came first, assessed up to 2 years
measure: The occurrence of adverse events and serious adverse events
timeFrame: during follow-up, up to 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing TianTan Hospital
state: Beijing
city: Beijing
country: China
facility: Sanbo Brain Hospital Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
References: