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Sintilimab, Pegaspargase and Anlotinib for Stage IV Natural Killer /T-cell Lymphoma

Phase 2
Conditions
Natural Killer/T-Cell Lymphoma, Nasal and Nasal-Type
Interventions
Drug: LEAP regimen
Registration Number
NCT04004572
Lead Sponsor
Rong Tao
Brief Summary

The purpose of this study is to evaluate the efficacy and safety of Sintilimab in combination with Pegaspargase and anlotinib in the treatment of stage IV NK/T-cell lymphoma patients unfit for high-dose chemotherapy.

Detailed Description

Stage IV NK/T-cell lymphoma has a poor prognosis, and autologous hematopoietic stem cell transplantation can improve the prognosis of patients who have achieved remission after chemotherapy. The median survival time for patients who were not suitable for transplantation was about 1 year. Asparaginase is the backbone drug for the treatment of NK/T-cell lymphoma. PD-1 antibody is effective for relapsed/refractory NK/T-cell lymphoma. Our previous study found that anlotinib is active in relapsed/refractory NK/T Cell lymphoma. This study is aimed to investigate the efficacy and safety of Sintilimab, a PD-1 antibody approved in China, in combination with Pegaspargase and anlotinib in the treatment of stage IV NK/T-cell lymphoma patients unfit for high-dose chemotherapy.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
37
Inclusion Criteria
  • Histopathology and immunohistochemistry confirmed diagnosis of NK/T-cell lymphoma according to WHO 2016 criteria.
  • Stage IV disease according Lugano 2014 staging system. Newly diagnosed patients, or relapsed disease without a history of asparaginase-containing regimen.
  • PET/CT or CT/MRI with at least one objectively evaluable lesion.
  • The age is greater than 65 years old. Those who are younger than 65 years should have a documented history unfit for high-dose combination chemotherapy (ie. high doses of methotrexate or high doses of dexamethasone, or autologous hematopoietic stem cell transplantation).
  • General status ECOG score 0-3 points.
  • The laboratory test 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. Coagulation : plasma fibrinogen ≥ 1.0g / L. Cardiac function: LVEF≥50%, ECG does not suggest any acute myocardial infarction, arrhythmia or atrioventricular conduction above I Blocking.

  • Sign the informed consent form.
  • Voluntary compliance with research protocols, follow-up plans, laboratory and auxiliary examinations.
Exclusion Criteria
  • Patients with a history of pancreatitis.
  • Active infection requires ICU treatment.
  • Concomitant HCV or HIV infection. Patients who are infected with HBV at the same time are not excluded.
  • Serious complications such as fulminant DIC.
  • Significant organ dysfunction: such as respiratory failure, NYHA classification ≥ 2 chronic congestive heart failure, decompensation Hepatic or renal insufficiency, high blood pressure and diabetes that cannot be controlled despite active treatment, and cerebral vascular thrombosis or hemorrhagic time within the past 6 months.
  • Pregnant and lactating women.
  • Had a history of autoimmune diseases, and disease was active in the last 6 months, and was still taking oral immunosuppression in the past three months.

For the treatment, the daily dose of oral prednisone is greater than 10 mg.

  • Those who were known to be allergic to drugs in the study regimen.
  • Patients with other tumors who require surgery or chemotherapy within 6 months.
  • Other experimental drugs are being used.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
LEAP RegimenLEAP regimenPegaspargase, 2500IU/m2, im, day 1 Sintilimab, 200mg, iv day1 Anlotinib, 8mg, oral, day 1-14 The LEAP regimen will be repeated every 3 weeks.
Primary Outcome Measures
NameTimeMethod
Complete response rateWeek 24 +/-7 days

The complete response rate will be assessed on week 24.

Secondary Outcome Measures
NameTimeMethod
Progression free survival1-year

Progression free survival is the time from entry onto the treatment until lymphoma progression or death of any reason.

Treatment-Related Adverse Events as Assessed by CTCAE v4.0Day 1 of each course of chemotherapy and then every 3 months for 1 year

Treatment-Related Adverse Events will be assessed and graded by NCI CTCAE v4.0.

Overall survival1-year

Overall survival is defiend as the time from entry onto the treatment until death of any reason

Overall response rateWeek 24 +/-7 days

The overall response rate will be assessed on Week 24

Trial Locations

Locations (1)

Xinhua Hospital

🇨🇳

Shanghai, Shanghai, China

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