The Efficacy and Safety of Chidamide, Anti-PD-1 Antibody in Combination With Pegaspargase Versus DDGP in the Treatment of Newly Diagnosed, Stage III to IV Extranodal Natural Killer/T-Cell Lymphoma

February 4, 2024 updated by: Zhao Weili, Ruijin Hospital
A multicenter, prospective, randomized, open-label, controlled trial to evaluate the efficacy and safety of chidamide, anti-PD1 antibody, and pegaspargase versus dexamethasone, cisplatin, gemcitabine, and pegaspargase (DDGP) in the treatment of newly diagnosed, stage III to IV extranodal natural killer/T-cell lymphoma.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This study will evaluate the efficacy and safety of chidamide, anti-PD1 antibody, and pegaspargase versus DDGP in the treatment of newly diagnosed, stage III to IV extranodal natural killer/T-cell lymphoma. Subjects will be randomly assigned 1:1 to chidamide, anti-PD1 antibody, and pegaspargase or DDGP regimen.

Patients in chidamide, anti-PD1 antibody, and pegaspargase group will receive 6 cycles of pegaspargase 2500IU/m2 intramuscularly on day1, anti-PD1 antibody 200mg intravenously on day 2, chidamide 30mg biw orally, every 21 days. Patients in DDGP group will receive 6 cycles of pegaspargase 2500IU/m2 intramuscularly on day1, cisplatin 20mg/m2 intravenously on days 1 through 4, dexamethasone 15mg/m2 intravenously on days 1 through 5, gemcitabine 800mg/m2 on day 1 and day 8, every 21 days.

Study Type

Interventional

Enrollment (Estimated)

142

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200025
        • Ruijin Hospital
        • Principal Investigator:
          • Weili Zhao
        • Contact:
        • Principal Investigator:
          • Shu CHENG
        • Sub-Investigator:
          • Jie XIONG

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Confirmed histological diagnosis of NKTCL
  • No previous anti-lymphoma treatment
  • Age 14-70 years
  • Ann Arbor stage III-IV
  • At least one measurable/evaluable site after diagnostic biopsy before treatment start
  • ECOG performance status of 0-2
  • Adequate hematological and organ function; i.e. ANC >1000 cells /mmc, platelet counts > 50.000/mmc, Hemoglobin > 8 g/dl AST, ALT > 1.5 x ULN; serum bilirubin > 2x ULN (patient with Gilbert disease can be enrolled), Serum creatinine > 2 x ULN or creatinine clearance > 50ml/min
  • Tumor tissue (fresh preferred, achievable tissue is also acceptable)
  • For women of childbearing potential a negative pregnancy test on day 1 of cycle 1 and agree to adopt adequate measure to avoid pregnancy during study treatment and for at least one year from EOT.
  • For men agreement to remain abstinent or to use barrier contraception
  • Signed Informed consent

Exclusion Criteria:

  • Confirmed histological diagnosis of aggressive NK cell leukemia
  • Early stage disease (AA stage I-II)
  • Evidence of suspect of CNS disease.
  • Has an active autoimmune disease that has required systemic treatment in past 2-years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs), including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associate with antiphospholipid syndrome, wegener's granulomatosis, Sjogren syndrome, guillan barreè syndrome, multiple sclerosis, vasculitis or glomerulonephritis. The following exception are allowed: patients with autoimmune related hypothyroidism or type I diabetes mellitus who are on stable treatment. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
  • Treatment with systemic immunosuppressive medications, including prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide and anti tumor necrosis factor (anti-TNF) agents within 2 weeks prior to cycle 1 day 1; inhaled corticosteroids are allowed.
  • Active infection requiring systemic therapy
  • History of (non-infectious) pneumonitis that required steroids; evidence of interstitial lung disease or active, non-infectious pneumonitis
  • Significant cardiovascular disease, myocardial infarction in the previous 3 months, unstable arrhythmias, or unstable angina.
  • History of other(s) infiltrating cancer(s) in the previous 3 years that were not treated with curative intent or who are still receiving anticancer therapy (including hormone therapy for breast or prostate cancer).
  • HBsAg, HCV or HIV positivity. Positive serology is admitted for HBV and HCV but DNA/RNA test must be negative
  • Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
  • Pregnant or lactating women
  • Administration of a live attenuated vaccine within 4 weeks before cyle 1 day 1. Patients must not receive live, attenuate vaccines, including influenza vaccines at any time during study.
  • Other uncontrollable medical condition that may that may interfere the participation of the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: chidamide, anti-PD1 antibody, and pegaspargase group
Drug: chidamide, anti-PD1 antibody, and pegaspargase
6 cycles of pegaspargase 2500IU/m2 intramuscularly on day1, anti-PD1 antibody 200mg intravenously on day 2, chidamide 30mg biw orally, every 21 days.
Active Comparator: DDGP
Drug: DDGP
6 cycles of pegaspargase 2500IU/m2 intramuscularly on day1, cisplatin 20mg/m2 intravenously on days 1 through 4, dexamethasone 15mg/m2 intravenously on days 1 through 5, gemcitabine 800mg/m2 on day 1 and day 8, every 21 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: Baseline up to data cut-off (up to approximately 2 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.
Baseline up to data cut-off (up to approximately 2 years)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0
Time Frame: From enrollment to study completion, a maximum of 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.
From enrollment to study completion, a maximum of 4 years
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.
At the end of Cycle 6 (each cycle is 21 days)
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.
At the end of Cycle 6 (each cycle is 21 days)
Overall survival
Time Frame: Baseline up to data cut-off (up to approximately 2 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.
Baseline up to data cut-off (up to approximately 2 years)
Percentage of Participants Achieving Meaningful Improvement in European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30)
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.
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ruijin Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

February 15, 2024

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

February 4, 2024

First Submitted That Met QC Criteria

February 4, 2024

First Posted (Estimated)

February 13, 2024

Study Record Updates

Last Update Posted (Estimated)

February 13, 2024

Last Update Submitted That Met QC Criteria

February 4, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RJ-NKTCL-3

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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