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Anti-PD-1 Antibody Combined With Pegaspargase in the Treatment of Advanced Stage NK/T-cell Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04096690
Recruitment Status : Recruiting
First Posted : September 20, 2019
Last Update Posted : March 11, 2020
Sponsor:
Information provided by (Responsible Party):
Zhao Weili, Ruijin Hospital

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.

Condition or disease Intervention/treatment Phase
Nasal Type Extranodal NK/T-Cell Lymphoma Drug: Pegaspargase Drug: Anti-PD-1 monoclonal antibody Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 22 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 10, 2019
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2022


Arm Intervention/treatment
Experimental: Anti-PD-1 antibody plus pegaspargase
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)
Drug: Pegaspargase
Pegaspargase 3750IU administered by intramuscular injection on Day 1 of each 21-day cycle for 6 cycles in induction treatment

Drug: Anti-PD-1 monoclonal antibody
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
Other Name: Tyvyt




Primary Outcome Measures :
  1. Complete response rate [ Time Frame: At the end of Cycle 6 (each cycle is 21 days) ]
    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 :
  1. Overall response rate [ Time Frame: At the end of Cycle 6 (each cycle is 21 days) ]
    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.

  2. Progression free survival [ Time Frame: Baseline up to data cut-off (up to approximately 4 years) ]
    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.

  3. Overall survival [ Time Frame: Baseline up to data cut-off (up to approximately 4 years) ]
    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.

  4. Duration of response [ Time Frame: Baseline up to data cut-off (up to approximately 4 years) ]
    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.

  5. EBV-DNA load change [ Time Frame: End of induction treatment (approximately 1 year) ]
    EBV-DNA load at each cycle for comparison

  6. Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 [ Time Frame: Baseline up to data cut-off (up to approximately 4 years) ]
    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.

  7. Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30) Domain Scores [ 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) ]
    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.

  8. Treatment related mortality [ Time Frame: Baseline up to data cut-off (up to approximately 4 years) ]
    Percentage of death related with treatment on the basis of investigator assessments


Other Outcome Measures:
  1. Circulating free Deoxyribonucleic Acid (cfDNA) monitoring [ Time Frame: Baseline up to data cut-off (up to approximately 4 years) ]
    CfDNA in peripheral blood assessed by local lab



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04096690


Locations
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China, Shanghai
Ruijin hospital Recruiting
Shanghai, Shanghai, China, 200025
Contact: Pengpeng XU, MD, PhD    86-21-64370045 ext 610707    xpproc@msn.com   
Principal Investigator: Weili ZHAO, MD, PhD         
Sub-Investigator: Pengpeng XU, MD, PhD         
Sponsors and Collaborators
Ruijin Hospital
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Responsible Party: Zhao Weili, First Deputy Director,Hematology Department, Ruijin Hospital
ClinicalTrials.gov Identifier: NCT04096690    
Other Study ID Numbers: RJ-NK-2019
First Posted: September 20, 2019    Key Record Dates
Last Update Posted: March 11, 2020
Last Verified: March 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Zhao Weili, Ruijin Hospital:
Anti-PD-1 antibody
Nasal Type Extranodal NK/T-Cell Lymphoma
Complete response rate
Safety
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, T-Cell
Lymphoma, Extranodal NK-T-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Pegaspargase
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents