Clinical trial NCT03936452: Combined Treatment of Sintilimab, Peg-aspargase Plus Anlotinib in NK/T Cell Lymphoma
Official title: An Open, Single-center, Phase II Study of Sintilimab, Peg-aspargase Plus Anlotinib "Sandwich"With Radiotherapy in Previously Untreated Stage I-II Extranodal NK/T Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Natural Killer/T-Cell Lymphoma, Nasal and Nasal-Type
Early Stage
Anlotinib
Peg-aspargase
Sintilimab
Phase Two
Open
Radiotherapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2019-05-03
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study aims to investigate the treatment of previously untreated stage I-II Extranodal NK/T Cell Lymphoma with sintilimab, peg-aspargase and anlotinib, "sandwich" with radiotherapy.

The primary endpoint is the complete response rate (CRR) at the end of the treatment, and the second endpoints are CRR after two cycles of the combined regimen (CRR2), overall response rate (ORR) at the end of the treatment, survival time (OS and PFS) and toxicities.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed NK/T cell lymphoma;
* Male or female: ≥18 and ≤70 years old;
* Eastern Cooperative Oncology Group (ECOG) status 0-3;
* Estimated survival time \> 3 months;
* No previous anti-tumor therapy including radiotherapy, chemotherapy, targeted therapy or stem cell transplantation;
* At least one evaluable or measurable lesion complying with Lugano 2014 Standard (evaluable lesion: the examination show increased uptake of lymph nodes or extranodal areas (higher than that of the liver) by 18F-Fluorodeoxyglucose/ Positron Emission Tomography (18FDG/PET) and the PET and/or Computed Tomography (CT) features coincide with lymphoma characteristics; measurable lesion: sarcoidal lesions were longer than 15 mm or extranodal lesions were longer than 10 mm, and accompanied by increased 18FDG uptake). Increased liver diffuse 18FDG uptake without measurable lesions should be excluded.
* The main organs function well, namely, the following requirements were met one week before admission: Blood routine WBC ≥ 3.5×109/L, Hb ≥ 100g/L and PLT ≥ 90×109/L; Heart and liver function were normal (total bilirubin ≤1.5×ULN, ALT and AST ≤ 2.5×ULN), renal function was normal (serum creatinine ≤1.5×upper limitation of normal (ULN)), and without abnormal coagulation function.
* Fertile patients must undergo pregnancy tests (serum or urine) within 14 days prior to study enrollment and the results are negative, and they are willing to use effective contraception during the trial;
* The imaging evaluation was Ann Arbor stage I/II.
* Voluntary participation and signed the informed consent, good compliance, with follow-up.

Exclusion Criteria:

* Patients allergic of any of drug in this regimen;
* Pregnant or lactating women
* Participated in other clinical trials within the 4 weeks prior to enrollment;
* Previous treatments with small molecule tyrosine kinase inhibitors, including familinib,sorafenib, sunitinib, regofinib, anlotinib, furquintinib, etc.
* Imaging showed tumors have involved important blood vessels (e.g. enveloping internal carotid artery/vein), or by investigators determine highly likely during the follow-up study and cause fatal hemorrhage
* History of severe hemorrhage, or any bleeding events with a severe grade of 3 or more in CTCAE 4.0 within 4 weeks prior to enrollment
* Blood pressure unable to be controlled ideally with single antihypertensive drug therapy (Systolic blood pressure \> 140 mmHg, Diastolic Blood Pressure \> 90 mmHg); Clinically significant cardiovascular disease (e.g. activity) including history of CVA (within 6 months), myocardial infarction (within 6 months), unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure; serious cardiac arrhythmia beyond drug control or potentially affecting experimental therapy.
* Active ulcer, intestinal perforation or intestinal obstruction;
* History of gastrointestinal perforation within 28 days prior to enrollment;
* Various factors affecting the oral administration and absorption of drugs (such as inability to swallow, after gastrointestinal resection, chronic diarrhea and intestinal obstruction, etc.);
* Abnormal coagulation or bleeding tendency (It must be satisfied that INR is under normal range without anticoagulant within 14 days prior to signing informed consent); patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or their analogues; on the premise that the international standardized ratio of prothrombin time (INR) is less than 1.5, small doses of warfarin (1 mg po, qd) or aspirin (no more than 100 mg qd) are allowed for preventive purposes.
* Arterial or venous thromboembolic events occurred within 6 months, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis (venous thrombosis caused by intravenous catheterization due to precancerous chemotherapy is excluded if it has been cured judged by the researchers) and pulmonary embolism.
* Renal insufficiency: routine urine tests indicate that urine protein is more than + +, or 24 hours urine protein is more than 1.0 g.
* Suffered major surgery within 28 days prior to enrollment;
* Received strong inhibitors of CYP3A4 within a week or strong inducers of CYP3A4 within 2 weeks prior to enrollment.
* Long-term non-healing wound or incomplete-healing fracture.
* Symptomatic brain metastases (confirmed or suspected);
* Severe or uncontrolled infections
* History of psychotropic drug abuse and unable to get rid of or with mental disorders;
* History of immunodeficiency, including HIV positive testing, or other acquired, congenital immunodeficiency disorders, or organ transplantation history;
* Previous and present objective evidences including history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia and severe impairment of pulmonary function.
* History of other malignancy within the last 5 years prior to enrollment, except for cured basal cell carcinoma of skin, cervix in situ carcinoma and superficial bladder cancer;Patients with concomitant diseases which could seriously endanger their own safety or could affect completion of the study according to investigators' judgment.

Primary outcomes:
measure: Complete response rate at the end of the treatment
timeFrame: 12 weeks after the last dose of the regimen
Secondary outcomes:
measure: Adverse events
timeFrame: Up to one year after the start of the study
measure: Progression Free Survival (PFS)
timeFrame: Up to three years after the start of the study
measure: Overall Survival (OS)
timeFrame: Up to three years after the start of the study
measure: Complete response rate after two cycles of the combined regimen
timeFrame: 4 weeks after the second dose of the combined regimen
measure: Overall response rate at the end of the treatment
timeFrame: 12 weeks after the last dose of the combined regimen
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Zhiming Li
role: PRINCIPAL_INVESTIGATOR
References: