Targeted Drug Combined With CHOP in the Treatment of Newly Diagnosed Peripheral T-cell Lymphoma

Study Overview
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Brief Summary
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This prospective，multi-center，open-label, controlled study will evaluate the efficacy and safety of targeted drug in combination with CHOP in treatment of newly diagnosed peripheral T-cell lymphoma.

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%. Patients with PTCL still have poor treatment response and prognosis under conventional CHOP regimen. There is no standard of care for those patients. Targeted drugs are warranted in this group of patients to improve survival. This prospective，multi-center，open-label, controlled study will evaluate the efficacy and safety of targeted drug in combination with CHOP in treatment of newly diagnosed peripheral T-cell lymphoma.

Official Title
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The Efficacy and Safety of Targeted Drug in Combination With Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in the Treatment of Newly Diagnosed Peripheral T-Cell Lymphoma

Conditions
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Peripheral T-cell Lymphoma

Intervention / Treatment
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* Drug: CHOP
* Drug: CHOP+X


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 with enough tumor sample for NGS Treatment naive Age ≥ 18 years Must has measurable lesion in CT or PET-CT prior to treatment ECOG 0,1,2 Informed consented Exclusion Criteria: ALCL,ALK positive, NK/T-cell leukemia, adult T-cell lymphoma/leukemia, T-LGL 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<50*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 or HCV-RNA positive

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CHOP<br>Patients in this arm will receive conventional CHOP regimen for 6 cycles | Drug: CHOP<br>* Cyclophosphamide 750mg/m2, ivgtt D1, doxorubicin 50mg/m2,ivgtt D1 Vincristine 1.4mg/m2（max 2mg）, ivgtt D1 Prednisone 60mg/m2 （max 100mg）,PO,D1-D5 every 21 days for total 6 courses<br>|
| Experimental: CHOP+X<br>Patients in this arm will receive targeted drug in combination with conventional CHOP regimen for 6 cycles, based on NGS results | Drug: CHOP+X<br>* X: X(i.e. targeted drug) will decided by NGS results as following. Decitabine 10mg/m2 ivgtt D-5 to-1 if with TP53 gene muation. Azacitadine 100mg/day ivgtt D-7 to -1 if with TET2/KMT2D gene mutation. Chidamide 20mg/day po D1,4,8,11 if with CREBBP/EP300 gene mutation. Lenalidomide 25mg/day po D1-10 if without gene mutation above. X will be added from the second cycle CHOP:Cyclophosphamide 750mg/m2, ivgtt D1, doxorubicin 50mg/m2,ivgtt D1 Vincristine 1.4mg/m2（max 2mg）, ivgtt D1 Prednisone 60mg/m2 （max 100mg）,PO,D1-D5 every 21 days for total 6 courses<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