Tislelizumab Combined Treatment in Refractory Extranodal NK/T-cell Lymphoma

Natural Killer/T-Cell Lymphoma, Nasal and Nasal-Type Clinical Trial

Official title:

Efficacy and Safety of Tislelizumab Combined Treatment in Refractory Natural Killer/T-cell Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05058755
• Other study ID #: XHLSG-NK-1903
• Status: Completed
• Phase: N/A
• Start date: September 17, 2021
• Est. completion date: December 30, 2023

Study information

• Verified date: February 2024
• Source: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: December 30, 2023
• Est. primary completion date: December 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Natural Killer/T-Cell Lymphoma, Nasal and Nasal-Type

Intervention

Drug:
• tislelizumab, azacytidine, lenalidomide
tislelizumab, 200mg, iv, day 1, every 21 days. azacytidine, 75mg/m2, ih, days 1-7, every 21 days. lenalidomide, 25mg, po, days 1-14, every 21 days.
• tislelizumab, etoposide, pegaspargase
tislelizumab, 200mg, iv, day 1, every 21 days. etoposide, 100mg, iv, days 1-3, every 21 days. pegaspargase, 2000U/m2, day 1, every 21 days

Locations

Country	Name	City	State
China	Xinhua Hospital,Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate	The overall response rate will be assessed on Week 12	Week 12 +/-7 days
Secondary	Complete response rate	The complete response rate will be assessed on Week 12	Week 12 +/-7 days
Secondary	Progression free survival	Progression free survival is the time from entry onto the treatment until lymphoma progression or death of any reason.	1-year
Secondary	Overall survival	Overall survival is defined as the time from entry onto the treatment until death of any reason	1-year
Secondary	Treatment-Related Adverse Events as Assessed by CTCAE v5.0	From day 1 of each course of chemotherapy to the 3 months after the last dose of therapy	Treatment-Related Adverse Events will be assessed and graded by NCI CTCAE v5.0.