Clinical trial NCT05058755: Tislelizumab Combined Treatment in Refractory Extranodal NK/T-cell Lymphoma
Official title: Efficacy and Safety of Tislelizumab Combined Treatment in Refractory Natural Killer/T-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Natural Killer/T-Cell Lymphoma, Nasal and Nasal-Type
Lead sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2021-09-28
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Natural killer/T-cell lymphoma (NKTCL) patients with relapsed/refractory disease had very poor outcome. Anti-PD-1 antibody showed promising results in response, but but the complete remission rate of was low. Some anti-PD-1 antibody based regimen showed higher and deeper response in NKTCL patients.

Detailed description: About 20-30% of early-stage patients and 40-60% of late-stage NKTCL patients will experience disease relapse and refractory disease, and the median survival time of relapsed patients is about 6 months. PD-1 antibody is an effective drug for the treatment of patients with relapsed/refractory NKTCL, but the response rate and complete remission rate of monotherapy are low. How to improve the prognosis of patients is an important way to try combination therapy. In this study, we aim to explore the effectiveness and safety of a novel anti-PD-1 antibody, tislelizumab, in combination with different drugs (tislelizumab plus azacytidine and lenalidomide, or tislelizumab plus etoposide and pegaspargase) to treat refractory NK/T.

Eligibility criteria: Inclusion Criteria:

1. Patients with biopsy histopathology, immunohistochemistry and EBER test meet ing the WHO 2016 diagnostic criteria for NK/T cell lymphoma.
2. With progressive disease after asparaginase-based combined chemotherapy
3. Have experienced multiple courses of PD-1/PD-L1 treatment with non-responsive or progressive disease.
4. PET/CT or CT/MRI with at least one measurable lesion or objectively evaluable lesion.
5. General ECOG score 0-3 points.
6. The laboratory examination within 1 week before enrollment meets the following conditions:

   Blood routine: Hb\>80g/L, PLT\>50×109/L. Liver function: ALT, AST, TBIL ≤ 2 times the upper limit of normal. Renal function: Cr is normal. Blood coagulation test: plasma fibrinogen ≥1.0g/L. Heart function: LVEF≥50%, ECG did not indicate any acute myocardial infarction, arrhythmia, or atrioventricular block of degree I or more.
7. Signed informed consent form.
8. Voluntarily comply with research protocols, follow-up plans, laboratory and auxiliary examinations.

Exclusion Criteria:

1. Patients with a history of pancreatitis (only patients who are planning to undergo PD1 combined with pegaspargase are excluded).
2. Severe infections require ICU treatment.
3. Combined HCV or HIV infection. Patients with HBV infection who receive antiviral treatment at the same time will not be excluded.
4. There are serious complications such as fulminant DIC.
5. Impairment of important organ functions: such as respiratory failure, chronic congestive heart failure with NYHA grade ≥2, decompensated liver or kidney insufficiency, hypertension and diabetes that cannot be controlled despite active treatment, nearly 6 years old There were cardio-cerebrovascular thrombotic or hemorrhagic events within months.
6. Pregnant and lactating women.
7. Have a history of autoimmune diseases, have disease activity in the past 6 months, and are still receiving oral immunosuppressive therapy within the past three months, and the daily dose of oral prednisone is greater than 10 mg.

Primary outcomes:
measure: Overall response rate
timeFrame: Week 12 +/-7 days
Secondary outcomes:
measure: Complete response rate
timeFrame: Week 12 +/-7 days
measure: Progression free survival
timeFrame: 1-year
measure: Overall survival
timeFrame: 1-year
measure: Treatment-Related Adverse Events as Assessed by CTCAE v5.0
timeFrame: Treatment-Related Adverse Events will be assessed and graded by NCI CTCAE v5.0.
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Xinhua Hospital,Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
affiliation: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
name: Rong Tao, MD
role: PRINCIPAL_INVESTIGATOR
References: