Back to resultsAnti-PD-1 Antibody Combined With Pegaspargase in the Treatment of Advanced Stage NK/T-cell Lymphoma
Primary Purpose
Nasal Type Extranodal NK/T-Cell Lymphoma
Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Pegaspargase
Anti-PD-1 monoclonal antibody
Sponsored by
About this trial
This is an interventional treatment trial for Nasal Type Extranodal NK/T-Cell Lymphoma focused on measuring Anti-PD-1 antibody, Nasal Type Extranodal NK/T-Cell Lymphoma, Complete response rate, Safety
Eligibility Criteria
Inclusion Criteria:
- Pathologically confirmed NK/T cell lymphoma based on 2016 WHO classification
- Treatment naive
- Age > 18 years
- Advanced stage
- Must has measurable lesion in CT or PET-CT prior to treatment
- ECOG 0,1,2
- Informed consented
Exclusion Criteria:
- Aggressive NK/T-cell leukemia
- Has accepted PD-1,PD-L1 or PD-L2 antibody before
- Has accepted autologous Stem cell transplantation before
- History of malignancy except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix 3 years prior to study treatment
- Uncontrollable cardio-cerebral vascular, coagulative, autoimmune, serious infectious disease
- Primary CNS lymphoma
- Lab at enrollment (Unless caused by lymphoma): Neutrophile<1.5*10^9/L ;Platelet<50*10^9/L; ALT or AST >3*ULN; Creatinine>2*ULN
- Other uncontrollable medical condition that may that may interfere the participation of the study
- Not able to comply to the protocol for mental or other unknown reasons Pregnant or lactation
- HIV infection
- HBV-DNA or HCV-RNA positive
- Diagnosed immunodeficiency or received systemic corticoid therapy 2 weeks prior to first dose.
- Received attenuated live vaccine 4 weeks prior to first dose.
Sites / Locations
- Ruijin hospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Anti-PD-1 antibody plus pegaspargase
Arm Description
Participants will receive induction treatment for six cycles of Anti-PD-1 antibody plus pegaspargase (21-day cycle) and Anti-PD-1 antibody monotherapy maintenance treatment for about 2 years (21-cycle)
Outcomes
Primary Outcome Measures
Complete response rate
Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria and 2016 Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy.
Secondary Outcome Measures
Overall response rate
Percentage of participants with overall response was determined on the basis of investigator assessments according to 2014 Lugano criteria and 2016 Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy.
Progression free survival
Progression-free survival was defined as the time from the date of diagnosis until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria2016 Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy, or death from any cause, whichever occurred first.
Overall survival
Overall survival in the overall study population was defined as the time from the date of diagnosis to the date of death from any cause. Reported is the percentage of participants with event.
Duration of response
Time from first occurrence of documented CR or PR to disease progression/relapse, or death from any cause for participants with a response of CR or PR. Tumor assessments were performed with PET-CT.
EBV-DNA load change
EBV-DNA load at each cycle for comparison
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30) Domain Scores
The EORTC QLQ-C30 is a health-related quality of life questionnaire. A higher score indicates better quality of life, with changes of 5 to 10 points considered to be a minimally important difference to participants.
Treatment related mortality
Percentage of death related with treatment on the basis of investigator assessments
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04096690
Brief Title
Anti-PD-1 Antibody Combined With Pegaspargase in the Treatment of Advanced Stage NK/T-cell Lymphoma
Official Title
The Efficacy and Safety of Anti-PD-1 Antibody in Combination With Pegaspargase in the Treatment of Newly Diagnosed, Stage III to IV Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Unknown status
Study Start Date
September 10, 2019 (Actual)
Primary Completion Date
December 2021 (Anticipated)
Study Completion Date
December 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ruijin Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This open-label, single arm study will evaluate the efficacy and safety of anti-PD-1 antibody in combination with pegaspargase in treatment of newly diagnosed advanced stage NK/T-cell lymphoma.
Detailed Description
Extranodal natural killer (NK)/T-cell lymphoma (ENKTL), nasal type, is a distinct and heterogeneous histopathologic subtype of non-Hodgkin lymphoma (NHL), accounting for 5%~10%. The frequency of ENKTL among NHL patients is significantly higher in Asia than in Western countries, with poor prognosis. L-asparaginase-based chemotherapy has improved the survival for these patients with advanced stage. However, there is no standard of care for those patients with advanced stage. Anti-PD-1 antibody has been proven its efficacy in relapsed or refractory NK/T cell lymphoma. This open-label, single arm study will evaluate the efficacy and safety of PD-1 antibody in combination with pegaspargase in treatment of newly diagnosed advanced stage NK/T-cell lymphoma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nasal Type Extranodal NK/T-Cell Lymphoma
Keywords
Anti-PD-1 antibody, Nasal Type Extranodal NK/T-Cell Lymphoma, Complete response rate, Safety
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Anti-PD-1 antibody plus pegaspargase
Arm Type
Experimental
Arm Description
Participants will receive induction treatment for six cycles of Anti-PD-1 antibody plus pegaspargase (21-day cycle) and Anti-PD-1 antibody monotherapy maintenance treatment for about 2 years (21-cycle)
Intervention Type
Drug
Intervention Name(s)
Pegaspargase
Intervention Description
Pegaspargase 3750IU administered by intramuscular injection on Day 1 of each 21-day cycle for 6 cycles in induction treatment
Intervention Type
Drug
Intervention Name(s)
Anti-PD-1 monoclonal antibody
Other Intervention Name(s)
Tyvyt
Intervention Description
Anti-PD-1 antibody 200mg administered intravenously (IV) on Day 2 of each 21-day cycle for 6 cycles in induction treatment Anti-PD-1 antibody 200mg administered intravenously (IV) on Day 1 of each 21-day cycle for up to 28 cycles in maintenance treatment
Primary Outcome Measure Information:
Title
Complete response rate
Description
Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria and 2016 Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy.
Time Frame
At the end of Cycle 6 (each cycle is 21 days)
Secondary Outcome Measure Information:
Title
Overall response rate
Description
Percentage of participants with overall response was determined on the basis of investigator assessments according to 2014 Lugano criteria and 2016 Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy.
Time Frame
At the end of Cycle 6 (each cycle is 21 days)
Title
Progression free survival
Description
Progression-free survival was defined as the time from the date of diagnosis until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria2016 Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy, or death from any cause, whichever occurred first.
Time Frame
Baseline up to data cut-off (up to approximately 4 years)
Title
Overall survival
Description
Overall survival in the overall study population was defined as the time from the date of diagnosis to the date of death from any cause. Reported is the percentage of participants with event.
Time Frame
Baseline up to data cut-off (up to approximately 4 years)
Title
Duration of response
Description
Time from first occurrence of documented CR or PR to disease progression/relapse, or death from any cause for participants with a response of CR or PR. Tumor assessments were performed with PET-CT.
Time Frame
Baseline up to data cut-off (up to approximately 4 years)
Title
EBV-DNA load change
Description
EBV-DNA load at each cycle for comparison
Time Frame
End of induction treatment (approximately 1 year)
Title
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
Description
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time Frame
Baseline up to data cut-off (up to approximately 4 years)
Title
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30) Domain Scores
Description
The EORTC QLQ-C30 is a health-related quality of life questionnaire. A higher score indicates better quality of life, with changes of 5 to 10 points considered to be a minimally important difference to participants.
Time Frame
Baseline (pre-dose [Hour 0] on Cycle1 Day1), Cycle3 Day 1, end of treatment (up to Month 6), every 3 months 1st year, every 6 months 2nd year, and 12 months thereafter up to data cut-off, up to approximately 4 years (cycle length = 21 days)
Title
Treatment related mortality
Description
Percentage of death related with treatment on the basis of investigator assessments
Time Frame
Baseline up to data cut-off (up to approximately 4 years)
Other Pre-specified Outcome Measures:
Title
Circulating free Deoxyribonucleic Acid (cfDNA) monitoring
Description
CfDNA in peripheral blood assessed by local lab
Time Frame
Baseline up to data cut-off (up to approximately 4 years)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Pathologically confirmed NK/T cell lymphoma based on 2016 WHO classification
Treatment naive
Age > 18 years
Advanced stage
Must has measurable lesion in CT or PET-CT prior to treatment
ECOG 0,1,2
Informed consented
Exclusion Criteria:
Aggressive NK/T-cell leukemia
Has accepted PD-1,PD-L1 or PD-L2 antibody before
Has accepted autologous Stem cell transplantation before
History of malignancy except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix 3 years prior to study treatment
Uncontrollable cardio-cerebral vascular, coagulative, autoimmune, serious infectious disease
Primary CNS lymphoma
Lab at enrollment (Unless caused by lymphoma): Neutrophile<1.5*10^9/L ;Platelet<50*10^9/L; ALT or AST >3*ULN; Creatinine>2*ULN
Other uncontrollable medical condition that may that may interfere the participation of the study
Not able to comply to the protocol for mental or other unknown reasons Pregnant or lactation
HIV infection
HBV-DNA or HCV-RNA positive
Diagnosed immunodeficiency or received systemic corticoid therapy 2 weeks prior to first dose.
Received attenuated live vaccine 4 weeks prior to first dose.
Facility Information:
Facility Name
Ruijin hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200025
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pengpeng XU, MD, PhD
Phone
86-21-64370045
Ext
610707
Email
xpproc@msn.com
First Name & Middle Initial & Last Name & Degree
Weili ZHAO, MD, PhD
First Name & Middle Initial & Last Name & Degree
Pengpeng XU, MD, PhD
12. IPD Sharing Statement
Learn more about this trial
Anti-PD-1 Antibody Combined With Pegaspargase in the Treatment of Advanced Stage NK/T-cell Lymphoma
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