Trial Title:
A Study of Selinexor in Combination With Temozolomide and Anti-PD-1 Antibody in Patients With Relapsed/Refractory Primary Central Nervous System Lymphoma
NCT ID:
NCT06556199
Condition:
Relapsed/Refractory Primary Central Nervous System Lymphoma
Conditions: Official terms:
Lymphoma
Temozolomide
Antibodies
Antibodies, Monoclonal
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Selinexor
Description:
Selinexor dose escalation: 40,60,80mg respectively every week, and dose expansion at the
RP2D of Selinexor,every 3 weeks for 6 cycles.
Arm group label:
selinexor-based treatment
Intervention type:
Drug
Intervention name:
Temozolomide
Description:
Temozolomide 150mg/m2 po d1-5 every 3 weeks for 6 cycles.
Arm group label:
selinexor-based treatment
Intervention type:
Drug
Intervention name:
Anti-PD-1 monoclonal antibody
Description:
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).
Arm group label:
selinexor-based treatment
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).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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) :
1. Bone marrow function: absolute value of neutrophils ≥1.5×10^9/L, platelets
≥80×10^9/L, hemoglobin ≥80 g/L;
2. 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);
3. Coagulation function: International standardized ratio (INR) and activated
partial thrombin time ≤1.5×ULN;
4. 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.
- Swallowing oral tablets/capsules without difficulty.
- Good compliance, willing to follow the visit schedule, dosing schedule, laboratory
examination and other test procedure.
Exclusion Criteria:
- 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.
- The presence of any life-threatening disease, medical condition, or organ system
dysfunction that the investigator believes may affect the patient's safety or
compliance with the study procedure.
- There are other conditions that the investigator considers inappropriate to
participate in this clinical trial.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
2nd Affiliated Hospital, School of Medicine, Zhejiang University
Address:
City:
Hanzhou
Zip:
310009
Country:
China
Status:
Recruiting
Contact:
Last name:
Wenbin Qian
Phone:
+8613605801032
Email:
qianwb@zju.edu.cn
Start date:
August 31, 2024
Completion date:
August 31, 2028
Lead sponsor:
Agency:
Second Affiliated Hospital, School of Medicine, Zhejiang University
Agency class:
Other
Source:
Second Affiliated Hospital, School of Medicine, Zhejiang University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06556199
