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

Sponsor

Henan Cancer Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT02733380

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B-cell Lymphoma	Drug: Chidamide Drug: Vinorelbine Drug: Liposomal Doxorubicin or mitoxantrone Drug: Dexamethasone Drug: Thalidomide	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2016

Anticipated Primary Completion Date :

May 1, 2020

Anticipated Study Completion Date :

May 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Chidamide combined with VDDT regimen 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 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 Drug: Vinorelbine 20mg/m2， IV on day 1 of each 14 day cycle until disease progression or unacceptable toxicity develops, up to 12 cycles Drug: Liposomal Doxorubicin or mitoxantrone 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 Drug: Dexamethasone 10mg/m2 , IV on day 1-5 of each 14 day cycle until disease progression or unacceptable toxicity develops, up to 12 cycles Drug: Thalidomide 100mg,Oral at night on each day until disease progression or unacceptable toxicity develops, up to 24 weeks

Arm

Intervention/Treatment

Experimental: Chidamide combined with VDDT regimen

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

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

Drug: Vinorelbine

20mg/m2， IV on day 1 of each 14 day cycle until disease progression or unacceptable toxicity develops, up to 12 cycles

Drug: Liposomal Doxorubicin or mitoxantrone

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

Drug: Dexamethasone

10mg/m2 , IV on day 1-5 of each 14 day cycle until disease progression or unacceptable toxicity develops, up to 12 cycles

Drug: Thalidomide

100mg,Oral at night on each day until disease progression or unacceptable toxicity develops, up to 24 weeks

Outcome Measures

Primary Outcome Measures

objective response rate [every 8 weeks until 1 year after last patient's enrollment]
the total proportion of patients with complete response（CR or CRu）and partial response（PR）
adverse events [from the date of first cycle of treatment to 1 year after last patient's enrollment]
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
abnormal laboratory examinations [from the date of first enrollment to 1 year after last patient's enrollment]
includes type, incidence, relationship with treatment and severity of abnormal laboratory examinations.
incidence and relationship with study drugs of grade 3-4 adverse events and abnormal laboratory examinations [from the date of first cycle of treatment to 1 year after last patient's enrollment]
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

Secondary Outcome Measures

progression-free survival [from the day of treatment to the date of first documented progression，up to 1 year after last patient's enrollment]
from date of first day of treatment to the date of first documented
duration of response [from the day of first documented response to first documented progression or death，up to 1 year after last patient's enrollment]
from the first day of documented response to disease progression or death.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 1.510^9/L; Platelets more than 9010^9/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