Chidamide Combined With VDDT Regimen in the Relapse and Refractory Diffuse Large B Cell Lymphoma

Study Overview
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Brief Summary
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This is a prospective phase II clinical trial to observe the efficacy and safety of Chidamide combined with VDDT(vinorelbine，liposomal doxorubicin，dexamethasone and thalidomide) in relapsed and refractory patients with diffuse large B-cell lymphoma(DLBCL).

Detailed Description
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There are one third of diffuse large B-cell Lymphoma patients suffering relapse and refractory, which are the major cause of death among these patients. Vinorelbine，liposomal doxorubicin，mitoxantrone, dexamethasone and thalidomide have been used in the therapy of patients who failed with Second-line treatments in our center. This regimen is well tolerated but the effect needs to be improved. Chidamide，a histone deacetylase inhibitor has been approved for the treatment of refractory T-cell lymphoma in China. The goal is to assess the efficacy and safety of chidamide combined with VDDT（vinorelbine，liposomal doxorubicin，dexamethasone and thalidomide） in relapse and refractory patients with diffuse large B-cell Lymphoma.

Official Title
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The Efficacy and Safety of Chidamide Combined With VDDT Regimen（Vinorelbine，Liposomal Doxorubicin，Dexamethasone and Thalidomide） in Relapse and Refractory Patients With Diffuse Large B Cell Lymphoma

Conditions
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Diffuse Large B-cell Lymphoma

Intervention / Treatment
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* Drug: Chidamide
* Drug: Vinorelbine
* Drug: Liposomal Doxorubicin or mitoxantrone
* Drug: Dexamethasone
* Drug: Thalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed as diffuse large B-cell Lymphoma based on the 2008 WHO classification of tumors of haematopoietic and lymphoid tissues Failed with second-line therapy Having at least one measurable lesions Age between 18 to 75 years old World health organization-Eastern Cooperative Oncology Group Performance Status (ECOG) 0-1 Neutrophils more than 1.5*10^9/L; Platelets more than 90*10^9/L Hemoglobin: more than 90g/L. Life expectancy no less than 3 months No receiving chemotherapy in 4 weeks before enrollment Agreeing to sign the written informed consents Exclusion Criteria: Pregnant ，lactating and patients at reproductive age who refuse to practice contraception QTc prolonging >450ms，ventricular tachycardia，atrial fibrillation，cardiac conduction block， myocardial infarction in less than 1 year， congestive heart failure，coronary heart disease which needs medication. Organ transplant recipients Active bleeding Thrombus，embolism，cerebral hemorrhage，cerebral infarction Important organ operation in less than 6 weeks Abnormal liver function（Note：total bilirubin >1.5 times the upper limit of normal，AST or ALT >2.5 times the upper limit of normal （Note：5 times the upper limit of normal for patients with liver involvement）），abnormal renal function（Note：serum creatinine >1.5 times the upper limit of normal），fluid and electrolyte disorders Mental illness or unable to sign the informed consent Drug addiction history or alcoholism which may interfere the experimental results. Researchers determine unsuited to participate in this trial Known allergy to any kind of study drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 combined with VDDT regimen<br>Chidamide 30mg，Oral twice a week with an interval of no less than 3 days combined with regimen：VDDT（Vinorelbine，Liposomal doxorubicin or mitoxantrone ，Dexamethasone and Thalidomide）：repeated every 14 days ，up to 12 cycles | Drug: Chidamide<br>* 30mg , Oral twice a week(with an interval of no less than 3 days,;e.g. Monday and Thursday，Tuesday and Friday) until disease progression or unacceptable toxicity develops<br>Drug: Vinorelbine<br>* 20mg/m2， IV on day 1 of each 14 day cycle until disease progression or unacceptable toxicity develops, up to 12 cycles<br>Drug: Liposomal Doxorubicin or mitoxantrone<br>* 20mg/m2, IV on day 1 of each 14 day cycle（Note：for patients who can not afford the liposomal doxorubicin，may be replaced into mitoxantrone 8mg/m2, IV on day1 of each 14 day cycle） until disease progression or unacceptable toxicity develops, up to 12 cycles<br>Drug: Dexamethasone<br>* 10mg/m2 , IV on day 1-5 of each 14 day cycle until disease progression or unacceptable toxicity develops, up to 12 cycles<br>Drug: Thalidomide<br>* 100mg,Oral at night on each day until disease progression or unacceptable toxicity develops, up to 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate | the total proportion of patients with complete response（CR or CRu）and partial response（PR） | every 8 weeks until 1 year after last patient's enrollment | 
| adverse events | any unfavorable and unintended sign , symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure | from the date of first cycle of treatment to 1 year after last patient's enrollment | 
| abnormal laboratory examinations | includes type, incidence, relationship with treatment and severity of abnormal laboratory examinations. | from the date of first enrollment to 1 year after last patient's enrollment | 
| incidence and relationship with study drugs of grade 3-4 adverse events and abnormal laboratory examinations | the incidence and relationship with study drugs of grade 3 or 4 adverse events (based on NCI CTC-AE v4.03) and abnormal laboratory examinations | from the date of first cycle of treatment to 1 year after last patient's enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival | from date of first day of treatment to the date of first documented | from the day of treatment to the date of first documented progression，up to 1 year after last patient's enrollment | 
| duration of response | from the first day of documented response to disease progression or death. | from the day of first documented response to first documented progression or death，up to 1 year after last patient's enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diffuse Large B-Cell Lymphoma, Relapsed and refractory, Histone deacetylase inhibitor, Chidamide