A Study of Selinexor in Combination With Temozolomide and Anti-PD-1 Antibody in Patients With Relapsed/Refractory Primary Central Nervous System Lymphoma

NCT06556199 | Recruiting Phase 1

• 1 other identifier: R202333
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Relapsed/Refractory Primary Central Nervous System Lymphoma

Outcome Measures

Primary Outcomes (2)

• Recommended phase 2 dose

  To determine the recommended phase 2 dose for Selinexor.

  Up to 21days

• 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.

  18 weeks

Secondary Outcomes (3)

• Progression-free survival (PFS)

  Up to 2 years after enrollment

• Overall survival (OS)

  Up to 2 years after enrollment

• Duration of response

  Up to 2 years after enrollment

Other Outcomes (2)

• ctDNA mutation and mean ctDNA concentration in serum and cerebrospinal fluid

  Up to 2 years after enrollment

• The levels of cytokine concentration in serum and cerebrospinal fluid

  Up to 2 years after enrollment

Study Arms (1)

selinexor-based treatment

EXPERIMENTAL

Drug: Selinexor; Drug: Temozolomide; Drug: Anti-PD-1 monoclonal antibody

Interventions

Selinexor DRUG

Selinexor dose escalation: 40,60,80mg respectively every week, and dose expansion at the RP2D of Selinexor,every 3 weeks for 6 cycles.

selinexor-based treatment

Temozolomide DRUG

Temozolomide 150mg/m2 po d1-5 every 3 weeks for 6 cycles.

selinexor-based treatment

Anti-PD-1 monoclonal antibody DRUG

The 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).

selinexor-based treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Primary central nervous system lymphoma (PCNSL) of B-cell origin confirmed by pathology (histology or cytology)
• Measurable disease was defined as at least ≥1.0cm in short-diameter by enhanced MRI.
• Recurrent/refractory PCNSL: Must have received at least one systemic treatment with methotrexate-based treatment.
• Any non-hematological toxicity associated with previous treatment should return to grade 1 or normal (except hair loss according to NCI CTCAE version 5.0)
• Bone marrow and organ function meet the following criteria (no blood transfusion within 14 days prior to screening, no G-CSF, no medication correction) :
• Bone marrow function: absolute value of neutrophils ≥1.5×10\^9/L, platelets ≥80×10\^9/L, hemoglobin ≥80 g/L;
• Liver function: serum total bilirubin ≤1.5×ULN (≤3.0×ULN, if there is liver metastasis); Glutamic oxalic aminotransferase (AST) and glutamic pyruvic aminotransferase (ALT) ≤2.5×ULN (≤5.0×ULN, if there is liver metastasis);
• Coagulation function: International standardized ratio (INR) and activated partial thrombin time ≤1.5×ULN;
• Renal function: serum creatinine ≤1.5×ULN or estimated creatinine clearance ≥60 mL/min (male: Cr (ml/min) = (140-age) × body weight (kg) /72× serum creatinine concentration (mg/dl); Female: Cr (ml/min) = (140- age) × body weight (kg) /85× serum creatinine concentration (mg/dl)
• Women of reproductive potential must agree to use highly effective methods of birth control during the period of therapy and for 6 months after the last dose of the study drug. Men who are sexually active must agree to use highly effective contraception during the period of therapy and for 6 months after the last dose.
• Can accept multiple MRI/CT and lumbar puncture examination.

You may not qualify if:

• 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.
• Active concurrent malignancy requiring active therapy.
• Prior treatment with temozolomide or anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs within 6 months prior to initial administration
• Have uncontrolled or significant cardiovascular disease, including (but not limited to) : Any of the following: congestive heart failure (NYHA Class III or IV);myocardial infarction; unstable angina; or the presence of an arrhythmia requiring treatment at the time of screening with a left ventricular ejection fraction (LVEF) \< 50% in the 6 months prior to initial dosing; Primary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restricted cardiomyopathy, undefined cardiomyopathy); A clinically significant history of prolonged QTc, grade II type II atrioventricular block or grade III atrioventricular block, or QTc interphase (method F) \> 470 msec (female) or \> 480msec (male);Atrial fibrillation (EHRA grade ≥2b);Patients with unmanageable hypertension were deemed unsuitable for participation in the study.
• Uncontrolled infections or infections that require intravenous antibiotic treatment.
• Chronic hepatitis B carriers with active hepatitis B or C infection (hepatitis B: acute hepatitis B, untreated chronic hepatitis B virus infection, HBV-DNA≥ the detection limit of each center; Hepatitis C: HCV RNA positive) or syphilis. Notes: Non-active HBV surface antigen (HBsAg) carriers, subjects with active HBV infection and persistent anti-HBV inhibition (HBV DNA \< each center detection limit), and subjects cured of HCV can be enrolled.
• Human immunodeficiency virus (HIV) infection
• Clinically significant gastrointestinal abnormalities that may affect drug intake, transport, or absorption (such as active gastrointestinal inflammation, chronic diarrhea, intestinal obstruction, etc.), or total gastrectomy or gastric banding surgery.
• Prior allogenic stem cell transplant.
• For female subjects, they are currently pregnant or breastfeeding.
• Allergy to the investigational drug or excipient.
• The patient has active mental illness, alcohol, drug or substance abuse.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

2nd Affiliated Hospital, School of Medicine, Zhejiang University

Hanzhou, Zhejiang, 310009, China

RECRUITING

MeSH Terms

Conditions

Recurrence

Interventions

selinexor; Temozolomide; spartalizumab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Xianggui Yuan

CONTACT

+8613989883884; yuanxg@zju.edu.cn

Wenbin Qian

CONTACT

+8613605801032; qianwb@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2024
• First Posted: August 15, 2024
• Study Start: August 31, 2024
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2028
• Last Updated: July 31, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)