Study Evaluating the Safety and Efficacy of C-CHOP in Untreated Subjects With Angioimmunoblastic T Cell Lymphoma

Study Overview
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Brief Summary
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This is a single-arm, open-label phase 2study of Chidamide in combination with CHOP in the treatment of subjects with untreated angioimmunoblastic T cell lymphoma.

Detailed Description
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This open-label, single arm study will evaluate the efficacy and safety of chidamide in combination with cyclophosphamide, doxorubicin, vincristine, and prednisolone or prednisone (CHOP) chemotherapy in previously untreated subjects with angioimmunoblastic T cell lymphoma. Subjects will receive 6 cycles of Chidamide 20mg, day 1,4,8,11, orally (PO) every 21 days, in addition to 6 cycles of CHOP chemotherapy IV every 21 days.

Official Title
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A Phase 2, Open-Label Study to Evaluate the Safety and Efficacy of Chidamide Combined With CHOP(Cyclophosphamide, Doxorubicin, Vincristine, Prednisone ) in Untreated Subjects With Angioimmunoblastic T Cell Lymphoma

Conditions
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Angioimmunoblastic T-cell Lymphoma

Intervention / Treatment
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* Drug: Chidamide
* Drug: Cyclophosphamide
* Drug: Doxorubicin
* Drug: Vincristine
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed angioimmunoblastic T cell lymphoma 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: Has accepted Chemotherapy 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 LVEF≤50% Lab at enrollment (Unless caused by lymphoma): Neutrophile<1.5*10^9/L ;Platelet<75*10^9/L; ALT or AST >2*ULN; AKP or bilirubin >1.5*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 Pregnant or lactation HIV infection If HbsAg positive, should check HBV DNA, DNA positive patients cannot be enrolled. If HBsAg negative but HBcAb positive (whatever HBsAb status), should check HBV DNA,DNA positive patients cannot be enrolled.

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: Chidamide plus CHOP<br>Participants received six 21-day cycles of chidamide, combined with six cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy (21-day cycles). | Drug: Chidamide<br>* Chidamide 20mg per day administered orally on Day 1, 4, 8, 11 of each 21-day cycle for 6 cycles<br>Drug: Cyclophosphamide<br>* Cyclophosphamide 750 milligrams per square metre (mg/m^2), administered intravenously (IV) on Day 1 of each 21-day cycle.<br>Drug: Doxorubicin<br>* Doxorubicin 50 mg/m^2 IV, administered on Day 1 of each 21-day cycle.<br>Drug: Vincristine<br>* Vincristine 1.4 mg/m^2 (maximum 2 mg) IV, administered on Day 1 of each 21-day cycle.<br>Drug: Prednisone<br>* Prednisone 60mg/m2 , Maximum 100 mg , (or equivalent prednisolone or methylprednisolone), administered orally on Days 1-5 of each 21-day cycle.<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 response(complete response and partial 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 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 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) | 
| Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | 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) ] |