This study aims to evaluate the efficacy and safety of the VPX regimen, a novel combination of teniposide, PD-1 monoclonal antibody and selinexor, in patients with relapsed/refractory (R/R) primary central nervous system lymphoma (PCNSL) who have progressed after high-dose methotrexate (HD-MTX)-based systemic therapy. By investigating this therapeutic approach, we seek to establish a new treatment paradigm that may improve clinical outcomes of this high-risk population.
This study will enroll patients aged 18-75 years with R/R PCNSL who have progressed after HD-MTX-based systemic therapy. Eligible participants will receive induction therapy with 2 cycles of VPX regimen followed by evaluation of contrast-enhanced magnetic resonance imaging (MRI) of the brain. Patients who got disease progression of stable disease will be withdrawn from this study. Patients who achieved partial remission(PR) or complete remission(CR)will receive consolidation treatment stratification as followings: Group A (ASCT-eligible): Patients will proceed to autologous stem cell transplantation (ASCT) as consolidation therapy. Group B (ASCT-ineligible): Patients will receive four additional cycles of VPX regimen, followed by whole-brain radiotherapy (WBRT) consolidation. After consolidation therapy, all responders will receive PD-1 monoclonal antibody therapy maintenance for up to 2 years, or until disease progression or unacceptable toxicity occurs.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
2 cycles of VPX regimen (21days per cycle) Teniposide: intravenous drip, 50mg d1-3; PD-1 monoclonal antibody: intravenous drip, 200mg d1; Selinixor: take 40mg orally, W1,60mg,W2,40mg biw,W3,cycle 1; 40mg, biw,cycle 2
TB preconditioning: Thiotepa intravenous drip 300mg/m2 d-6-d-5; Busulfan: intravenous drip, 0.8mg/kg q6h d-4--d2; followed by autologous peripheral stem cells infusion at day 0
4 cycles of VPX regimen (21days per cycle) Teniposide: intravenous drip, 50mg d1-3; PD-1 monoclonal antibody: intravenous drip, 200mg d1; Selinixor: take 40mg orally biw, cycle 3-6;
whole brain radiotherapy: CTV1: 20-30Gy/10fractions GTVp: 25-40Gy/10fractions
PD-1 monoclonal antibody for up to 2 years intravenous infusion, 200mg d1 (21days per cycle)
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, China
RECRUITINGOverall response rate(ORR)
The rate of patients who achieved CR or PR after induction therapy with 2 cycles of VPX regimen
Time frame: At the end of 2 cycles of VPX regimen (each cycle is 21 days)
2-year progression-free survival(PFS)
PFS will be assessed from the first day of treatment to date of progression, relapse, death or end of follow-up.
Time frame: From enrollment to 2-year after the end of last patient's treatment
Major adverse events
The safety and tolerability of the VPX regimen measured by the major adverse events.
Time frame: From enrollment to 1 month after induction therapy
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