Azacitidine Combined With Chidamide in the Treatment of Newly Diagnosed PTCL Unfit for Conventional Chemotherapy

Study Overview
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Brief Summary
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This prospective, open-label, single-arm study will evaluate the efficacy and safety of azacitidine in combination with chidamide in treatment of newly diagnosed peripheral T-cell lymphoma unfit for conventional chemotherapy.

Detailed Description
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Peripheral T-cell lymphoma (PTCL is a distinct and heterogeneous histopathologic subtype of non-Hodgkin lymphoma (NHL), accounting for  10%. CHOP regimen has been widely used in PTCL patients even with unfavourable prognosis, with 5-year overall survival rate of 38.5%. Elderly patients seldom benefit from conventional CHOP regimen. A study showed that CR rate was only 18.1% in elderly patients (median age of 80 years old, ranging from 56 to 93 years old). Azacitidine combined with romidepsin has been proved efficient in relasped or refractory PTCL, with CR rate of 55%. This prospective, open-label, single-arm study will evaluate the efficacy and safety of azacitidine in combination with Chidamide in treatment of newly diagnosed peripheral T-cell lymphoma unfit for conventional chemotherapy.

Official Title
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The Efficacy and Safety of Azacitidine in Combination With Chidamide in the Treatment of Newly Diagnosed Peripheral T-Cell Lymphoma Unfit for Conventional Chemotherapy

Conditions
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Peripheral T-cell Lymphoma

Intervention / Treatment
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* Drug: Azacitidine
* Drug: Chidamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed peripheral T-cell lymphoma based on 2016 WHO classification Treatment naive Age ≥ 18 years Unfit for converntional chemotherapy meeting criteria as following but not limited to: age ≥75, ECOG >2，ADL<100 or CCI>1. Must has measurable lesion in CT or PET-CT prior to treatment Expected lifetime ≥ 3 months Informed consented Exclusion Criteria: Has accepted localized or systemic anti-lymphoma treatment 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 prior to study treatment Uncontrollable cardio-cerebral vascular, coagulative, autoimmune, serious infectious disease Primary CNS lymphoma Left EF≤ 50% Lab at enrollment (Unless caused by lymphoma): Neutrophile<1.5*10^9/ L ;Platelet<75*10^9/L; ALT or AST >2*ULN; Creatinine>1.5*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 Patients with mentally disorders or other reasons unable to fully comply with the study protocol Pregnant or lactation HIV infection HBV-DNA and HCV-RNA undectable.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aza+Chida<br>Azacitidine ivgtt D1-7 Chindamide 30mg,PO,twice a week Every 21 days for total 6 courses | Drug: Azacitidine<br>* 100mg D1-7<br>Drug: Chidamide<br>* 30mg BIW PO<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate | Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria | At the end of Cycle 6 (each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | Percentage of participants with overall response was determined on the basis of investigator assessments according to 2014 Lugano criteria | At the end of Cycle 6 (each cycle is 21 days) | 
| 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 criteria,or death from any cause, whichever occurred first. | Baseline up to data cut-off (up to approximately 4 years) | 
| Overall survival | Overall survival 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. of disease progression or relapse, using 2014 Lugano criteria,or death from any cause, whichever occurred first. | Baseline up to data cut-off (up to approximately 4 years) | 
| 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. | Baseline up to data cut-off (up to approximately 4 years) | 
| Treatment related mortality | Percentage of death related with treatment on the basis of investigator assessments | Baseline up to data cut-off (up to approximately 4 years) | 
| Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE | 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 | Baseline up to data cut-off (up to approximately 4 years) | 
| 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. | : 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peripheral T-cell lymphoma, Targeted therapy, Chemo-free therapy