Clinical Trial of Chidamide Combined With CHOP in Peripheral T-cell Lymphoma Patients

Study Overview
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Brief Summary
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The purpose of this dose-escalation study is to assess the safety and tolerability of treatment with Chidamide in a range of doses combined with CHOP in fixed dose in patients with newly diagnosed peripheral T-cell lymphoma.

Detailed Description
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The purpose of this study is to assess the tolerability and safety include adverse events, vital signs, laboratory tests, etc., of a range of doses of chidamide combined with CHOP in peripheral T-cell lymphoma patients, and to determine the dose limit toxicity and the maximum tolerable dose.

Official Title
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An Open-label, Multi-center, Phase Ib Clinical Trial of Chidamide Combined With CHOP in Newly Diagnosed Peripheral T-cell Lymphoma Patients

Conditions
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Peripheral T-cell Lymphoma

Intervention / Treatment
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* Drug: Chidamide
* Drug: cyclophosphamide
* Drug: adriacin
* Drug: vincristine
* Drug: prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female aged 18-65 years old; Histopathologically confirmed Peripheral T -cell Lymphoma (PTCL) including: PTCL-unspecified; Angioimmunoblastic T-cell lymphoma; Anaplastic large cell lymphoma, ALK positive or negative; Subcutaneous panniculitis T-cell lymphoma; Cutaneous / T-cell lymphoma; Other T-cell lymphoma that investigators consider to be appropriate to be enrolled; Patients have not received anti-tumor therapy; In any Ann Arbor disease stage; ECOG performance status 0-1; Patients without bone marrow involvement. The absolute number of neutrophile is no less then 2.0 * 10^9/L, platelet no less then 100 * 10^9/L. And the concentration of hemoglobin is no less than 110 g/L; Life expectancy is no less than 6 months; Patients who have signed the Informed Consent Form. Exclusion Criteria: Patients who have central nervous system or meninges involvements; Patients have been treated by radiotherapy, chemotherapy or immunotherapy for PTCL; Patients have uncontrollable or significant cardiovascular disease including: history of myocardial infarction; uncontrollable angina within the 6 months before screening, or taking anti-angina drugs at the time of screening; history of congestive heart failure, or the left ventricular ejection fraction (LVEF) is < 50% at the time of screening; clinically significant ventricular arrhythmia such as ventricular tachycardia, ventricular fibrillation or torsades de pointes; History of supraventricular arrhythmia or nodal arrhythmia that could not been controlled by drug or need a pacemaker; History of cardiomyopathy; History of clinically significant QTc interval prolongation, or QTc interval > 450 ms at screening; Coronary disease which is with symptoms and needs drug therapy; Patients have undergone organ transplantation; Patients with thromboembolic disease, hematencephalon or cerebral infraction within 4 weeks before screening, or patients who are under anticoagulant therapy; Patients with clinically significant abnormalities in gastrointestinal tract, such as dysphagia, chronic diarrhea and intestinal obstruction which may affect the uptake,transformation and absorption of the drug; Patients with active infections, including active bacterial,viral,fungoid, mycobacterium, parasite infections (but not including hyponychium fungoid infection), or infections which need not be treated by intravenous antibody therapies, or antiviral therapies, or any serious infection need to be treated by hospitalization; Patients who have been conducted the surgery on a major organ in less than 6 weeks; Hepatic function: Serum total bilirubin > 1.5 fold of normal range; ALT/AST > 2.5 folds of normal range or 5 folds for liver metastasis; Renal function: Serum creatine > 1.5 folds of normal range; Patients with other malignancies in the past or now (except basal cell carcinoma, squamous-cell carcinoma or carcinoma in situs of cervix that has been adequately treated),unless the malignancy has been radically treated and there has been no evidence of recurrence for 5 years; Pregnant or lactating women and patients in childbearing age who will not carry out birth control; Patients with mental disorders, which may affect understanding and execution of informed consent or the compliance of the study; Drug abuse or long term alcoholism that could affect the evaluation for the study results; Patients considered by investigators not suitable for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: study drugs<br>Lead-in period is 4 days. Patients take a single dose of Chidamide tablet, then off for 3 days before the first cycle begins. In the subsequent treatment cycles, Chidamide tablets are given orally on Day 1,4,8 and 11 of each cycle. Cyclophosphamide, adriacin and vincristine are given in intravenous infusion on Day 1. On Day 1 to 5, prednisone is given orally. Treatment cycles are repeated every 3 weeks .The combination therapy lasts for at most 6 cycles. Patients enter the single agent therapy if attained complete response after 6-cycle combination therapy. In this stage, patients take chidamide orally on Day 1, 4, 8 and 11 of each cycle. | Drug: Chidamide<br>* In the lead-in period, patients take a single dose of Chidamide tablet on the first day and then off for 3 days before the first cycle begins. In the subsequent treatment cycles, Chidamide tablets are given orally on Day 1,4,8 and 11 of each cycle.<br>* Other names: CS055;Drug: cyclophosphamide<br>* On Day 1, cyclophosphamide is given in a 20-minute intravenous (IV) infusion at 750 mg/m^2 in 5 minutes after chidamide administration<br>* Other names: CTX;Drug: adriacin<br>* On Day 1, Adriacin is given in a 20-minute IV infusion at 50 mg/m^2 soon after cyclophosphamide administration.<br>* Other names: ADR;Drug: vincristine<br>* On Day 1, vincristine is given in IV infusion at 1.4 mg/m^2 after adriacin administration.<br>* Other names: VCR;Drug: prednisone<br>* On Day 1 to 5, prednisone is given orally at 100 mg once a day<br>* Other names: PED;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| dose-limiting toxicity (DLT) |  | Day 1 - 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events |  | About 21 weeks | 
| complete response rate |  | About 21 weeks | 
| Duration of response |  | About 21 weeks | 
| Progression free survival |  | About 21 weeks | 
| Objective response rate |  | About 21 weeks | 
| Overall survival |  | About 21 weeks | 
| Area under the concentration versus time curve (AUC) |  | Day 1 of the lead-in period and Day 1 of the combination therapy | 
| Peak plasma concentration (Cmax) |  | Day 1 of the lead-in period and Day 1 of the combination therapy | 
| Time of Cmax (Tmax) |  | Day 1 of the lead-in period and Day 1 of the combination therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peripheral T-cell lymphoma, PTCL, chidamide, CHOP, phase Ib