This study is a prospective, single-arm, open label, Phase Ib/II clinical study to evaluate the safety and efficacy of selinexor in combination with temozolomide and anti-PD-1 monoclonal antibody in patients with relapsed/refractory primary central nervous system lymphoma(PCNSL). Phase Ib used a "3+3" dose-climbing design to confirm the safety, maximum-tolerated dose (MTD,if any) and recommended phaseII dose (RP2D) of selinexor in combination with fixed dose of temozolomide and anti-PD-1 monoclonal antibody for 6 cycles. Phase II was a comprehensive evaluation of efficacy and safety. Subjects who achieved complete remission or partial remission were treated with anti-PD-1 monoclonal antibody maintenance therapy until disease progression or recurrence, intolerance of toxicity, death, loss of follow-up, withdrawal of notification (whatever happened first).
Aged between 18 and 75 (inclusive).
Participants must be able to understand and be willing to sign a written informed consent document.
Eastern Cooperative Oncology Group performance status 0 to 3.
Life expectancy of ≥ 3 months (in the opinion of the investigator).
Pathological diagnosis was T cell lymphoma.
Anti-tumor therapy with chemotherapy, radiotherapy, immunotherapy or antibody drugs, or Chinese herbal medicine with anti-tumor indications, small-molecule targeted therapy within 2 weeks, monoclonal antibody-coupled drugs or cytotoxin therapy within 10 weeks, and autologous stem cell transplantation within 6 months before the first administration.
Participation in another clinical study with an investigational product during the 4 weeks prior to the first day of study treatment.
Patients who use systemic adrenal corticosteroids for more than 5 days within 14 days prior to medication or who need to take >10mg of dexamethasone or equivalent drugs daily to control CNS disease.
Single group
Selinexor
DrugSelinexor dose escalation: 40,60,80mg respectively every week, and dose expansion at the RP2D of Selinexor,every 3 weeks for 6 cycles.
Temozolomide
DrugTemozolomide 150mg/m2 po d1-5 every 3 weeks for 6 cycles.
Anti-PD-1 monoclonal antibody
DrugThe dose of anti-PD-1 monoclonal antibody is fixed dose 200 mg intravenously every 3 weeks until until disease progression or recurrence, intolerance of toxicity, death, loss of follow-up, withdrawal of notification (whatever happened first).
Recommended phase 2 dose
To determine the recommended phase 2 dose for Selinexor.
Objective response rate (ORR) for Phase II study
The objective response rate (ORR) is defined as the proportion of patients with CR or PR at the end of induction treatment.
Progression-free survival (PFS)
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Overall survival (OS)
OS is defined as the duration of time from start of treatment to time of death.
Duration of response
The duration of overall response is measured from the time achieving ORR to time of progression, relapse or death, whichever occurs first.
ctDNA mutation and mean ctDNA concentration in serum and cerebrospinal fluid
Types of ctDNA mutations and frequency are measured by next generation sequencing. The mean ctDNA concentration is the concentration of ctDNA expressed as mean tumor molecules /ml at specific time points.
The levels of cytokine concentration in serum and cerebrospinal fluid
The levels of cytokine will be analyzed by ELISA in all patients recruited at Baseline and specific time point. The cytokine profile includes IL-6, IL-10, TNF-α, IFN-γ, IL-2 and IL-4
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