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

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Enrolling; Phase 2

Conditions: Primary Central Nervous System Lymphoma

Treatments: Drug: Pomalidomide; Drug: Orelabrutinib; Drug: Rituximab; Drug: Methotrexate

Study type: Interventional

Funder types: Other

Identifiers

NCT05390749

PUMCH-NHL-013

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

POR-ROMTX

Experimental group

Description:

The experimental arm 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.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).

Treatment:

Drug: Rituximab

Drug: Methotrexate

Drug: Pomalidomide

Drug: Orelabrutinib