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

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

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.

Study Overview

• Status: Completed
• Conditions: Natural Killer/T-Cell Lymphoma, Nasal and Nasal-Type
• Intervention / Treatment: Drug: tislelizumab, azacytidine, lenalidomide; Drug: tislelizumab, etoposide, pegaspargase

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.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200092
      • Xinhua Hospital,Shanghai Jiao Tong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TALE regimen; tislelizumab plus azacytidine and lenalidomide	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.; Other Names: Tileilizhu Dankang
Experimental: TEPA regimen; tislelizumab plus etoposide and pegaspargase	Drug: 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; Other Names: Tileilizhu Dankang

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	The overall response rate will be assessed on Week 12	Week 12 +/-7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Progression free survival is the time from entry onto the treatment until lymphoma progression or death of any reason.	1-year
Complete response rate	The complete response rate will be assessed on Week 12	Week 12 +/-7 days
Overall survival	Overall survival is defined as the time from entry onto the treatment until death of any reason	1-year
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.

Collaborators and Investigators

• Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• Investigators: Principal Investigator: Rong Tao, MD, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2021
• Primary Completion (Actual): December 30, 2022
• Study Completion (Actual): December 30, 2023

Study Registration Dates

• First Submitted: September 17, 2021
• First Submitted That Met QC Criteria: September 17, 2021
• First Posted (Actual): September 28, 2021

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Etoposide; Lenalidomide; Azacitidine; Pegaspargase; Tislelizumab
• Other Study ID Numbers: XHLSG-NK-1903

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No