Clinical trial NCT06255795: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Extranodal Natural Killer T Cell Lymphoma
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2024-02-13
Enrollment: 142
Sex: ALL
Minimum age (years): 14
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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 \&gt;1000 cells /mmc, platelet counts \&gt; 50.000/mmc, Hemoglobin \&gt; 8 g/dl AST, ALT \&gt; 1.5 x ULN; serum bilirubin \&gt; 2x ULN (patient with Gilbert disease can be enrolled), Serum creatinine \&gt; 2 x ULN or creatinine clearance \&gt; 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

Primary outcomes:
measure: Progression free survival
timeFrame: Baseline up to data cut-off (up to approximately 2 years)
Secondary outcomes:
measure: Complete response rate
timeFrame: At the end of Cycle 6 (each cycle is 21 days)
measure: Overall response rate
timeFrame: At the end of Cycle 6 (each cycle is 21 days)
measure: Overall survival
timeFrame: Baseline up to data cut-off (up to approximately 2 years)
measure: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0
timeFrame: From enrollment to study completion, a maximum of 4 years
measure: Percentage of Participants Achieving Meaningful Improvement in European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30)
timeFrame: 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)
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital
state: Shanghai
Study officials:
References: