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出境医 / 临床实验 / Combined Treatment of Sintilimab, Peg-aspargase Plus Anlotinib in NK/T Cell Lymphoma

Combined Treatment of Sintilimab, Peg-aspargase Plus Anlotinib in NK/T Cell Lymphoma

Study Description
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, combined with radiotherapy. The primary endpoint is response rate (complete response rate and overall response rate), and the second endpoints are survival time (OS and PFS) and toxicities.

Condition or disease Intervention/treatment Phase
Natural Killer/T-Cell Lymphoma, Nasal and Nasal-Type Early Stage Anlotinib Peg-aspargase Sintilimab Phase Two Open Drug: Sintilimab Phase 2

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open, Multi-center, Phase II Study of Sintilimab, Peg-aspargase Plus Anlotinib in Previously Untreated Stage I-II Extranodal NK/T Cell Lymphoma
Actual Study Start Date : April 28, 2019
Estimated Primary Completion Date : April 30, 2020
Estimated Study Completion Date : December 31, 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: Treatment arm
Sintilimab 200mg ivdrip D1 Peg-aspargase 2500U/m2 im D1 Anlotinib 12 mg po D1-14 repeat every three weeks
Drug: Sintilimab
Sintilimab 200mg ivdrip D1 Anlotinib 12mg po D1-14 Peg-aspargase 2500U/m2 im D1 combined with radiotherapy
Other Names:
  • Peg-aspargase
  • Anlotinib

Outcome Measures
Primary Outcome Measures :
  1. Overall response rate [ Time Frame: 12 weeks after the initiation of the treatment. ]
    The overall response rate

  2. Complete response rate [ Time Frame: 12 weeks after the initiation of the treatment. ]

Secondary Outcome Measures :
  1. Adverse events [ Time Frame: Up to one year after the start of the study ]
    All the adverse events of the patients related will be assessed and graded by NCI CTCAE v4.0

  2. Progression Free Survival (PFS) [ Time Frame: Up to three years after the start of the study ]
    PFS was defined as time from study registration to first disease progression or death whichever occurred first, otherwise subject data were censored at time last known disease free.

  3. Overall Survival (OS) [ Time Frame: Up to three years after the start of the study ]
    OS was defined as time from study registration to death, and otherwise censored at time last known alive.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed NK/T cell lymphoma;
  • Male or female: 18-70 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.
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Zhiming Li, Dr. +86-020-87343765 lizhm@sysucc.org.cn
Contact: Peng Sun, Dr. +86-020-87343363 sunp@sysucc.org.cn

Locations
Layout table for location information
China, Guangdong
Sun Yat-Sen University Cancer Center Recruiting
Guandong, Guangdong, China, 510060
Contact: Zhiming Li, Dr.    +86-020-87343765    lizhm@sysucc.org.cn   
China, Guangxi
Guangxi Medicanl Universitu Affiliated Tumor Hospital Recruiting
Nanning, Guangxi, China, 530000
Principal Investigator: Hong Ceng         
The First Affiliated Hospital of Guangxi Medical University Recruiting
Nanning, Guangxi, China, 530000
Principal Investigator: Jie Ma         
China, Hunan
Hunan Cancer Hospital Recruiting
Changsha, Hunan, China, 410000
Principal Investigator: Hui Zhou         
China, Sichuan
West China Hospital.Sichuan University Recruiting
Chengdu, Sichuan, China, 610000
Principal Investigator: Liqun Zou         
China, Yunnan
Yunan Cancer Hospital Recruiting
Kunming, Yunnan, China, 650000
Principal Investigator: Chunlin Gao         
Sponsors and Collaborators
Sun Yat-sen University
Tracking Information
First Submitted Date  ICMJE May 1, 2019
First Posted Date  ICMJE May 3, 2019
Last Update Posted Date September 27, 2019
Actual Study Start Date  ICMJE April 28, 2019
Estimated Primary Completion Date April 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 2, 2019)
  • Overall response rate [ Time Frame: 12 weeks after the initiation of the treatment. ]
    The overall response rate
  • Complete response rate [ Time Frame: 12 weeks after the initiation of the treatment. ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 2, 2019)
  • Adverse events [ Time Frame: Up to one year after the start of the study ]
    All the adverse events of the patients related will be assessed and graded by NCI CTCAE v4.0
  • Progression Free Survival (PFS) [ Time Frame: Up to three years after the start of the study ]
    PFS was defined as time from study registration to first disease progression or death whichever occurred first, otherwise subject data were censored at time last known disease free.
  • Overall Survival (OS) [ Time Frame: Up to three years after the start of the study ]
    OS was defined as time from study registration to death, and otherwise censored at time last known alive.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combined Treatment of Sintilimab, Peg-aspargase Plus Anlotinib in NK/T Cell Lymphoma
Official Title  ICMJE An Open, Multi-center, Phase II Study of Sintilimab, Peg-aspargase Plus Anlotinib in Previously Untreated Stage I-II Extranodal NK/T Cell Lymphoma
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, combined with radiotherapy. The primary endpoint is response rate (complete response rate and overall response rate), and the second endpoints are survival time (OS and PFS) and toxicities.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Natural Killer/T-Cell Lymphoma, Nasal and Nasal-Type
  • Early Stage
  • Anlotinib
  • Peg-aspargase
  • Sintilimab
  • Phase Two
  • Open
Intervention  ICMJE Drug: Sintilimab
Sintilimab 200mg ivdrip D1 Anlotinib 12mg po D1-14 Peg-aspargase 2500U/m2 im D1 combined with radiotherapy
Other Names:
  • Peg-aspargase
  • Anlotinib
Study Arms  ICMJE Experimental: Treatment arm
Sintilimab 200mg ivdrip D1 Peg-aspargase 2500U/m2 im D1 Anlotinib 12 mg po D1-14 repeat every three weeks
Intervention: Drug: Sintilimab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 2, 2019)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date April 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed NK/T cell lymphoma;
  • Male or female: 18-70 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Zhiming Li, Dr. +86-020-87343765 lizhm@sysucc.org.cn
Contact: Peng Sun, Dr. +86-020-87343363 sunp@sysucc.org.cn
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03936452
Other Study ID Numbers  ICMJE B2019-048-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Li Zhiming, Sun Yat-sen University
Study Sponsor  ICMJE Sun Yat-sen University
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Sun Yat-sen University
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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