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

Phase 2

• Conditions: Diffuse Large B-cell Lymphoma
• Interventions: Drug: Chidamide; Drug: Vinorelbine; Drug: Liposomal Doxorubicin or mitoxantrone; Drug: Dexamethasone; Drug: Thalidomide

• Registration Number: NCT02733380
• Lead Sponsor: Henan Cancer Hospital

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).

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 Timeline

• Study First Submitted: 2016-03-25
• Study First Submitted QC: 2016-04-08
• Study First Posted: 2016-04-11
• Study Start: 2016-05
• Status Verified: 2018-08
• Last Update Submitted: 2020-03-31
• Last Update Posted: 2020-04-01
• Primary Completion: 2020-05
• Study Completion: 2021-05

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Diagnosed as diffuse large B-cell Lymphoma based on the 2008 WHO classification of tumors of haematopoietic and lymphoid tissues
2. Failed with second-line therapy
3. Having at least one measurable lesions
4. Age between 18 to 75 years old
5. World health organization-Eastern Cooperative Oncology Group Performance Status (ECOG) 0-1
6. Neutrophils more than 1.5*10^9/L; Platelets more than 90*10^9/L Hemoglobin: more than 90g/L.
7. Life expectancy no less than 3 months
8. No receiving chemotherapy in 4 weeks before enrollment
9. Agreeing to sign the written informed consents

Exclusion Criteria

1. Pregnant ，lactating and patients at reproductive age who refuse to practice contraception
2. 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.
3. Organ transplant recipients
4. Active bleeding
5. Thrombus，embolism，cerebral hemorrhage，cerebral infarction
6. Important organ operation in less than 6 weeks
7. 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
8. Mental illness or unable to sign the informed consent
9. Drug addiction history or alcoholism which may interfere the experimental results.
10. Researchers determine unsuited to participate in this trial
11. Known allergy to any kind of study drugs

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Chidamide combined with VDDT regimen	Liposomal Doxorubicin or mitoxantrone	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
Chidamide combined with VDDT regimen	Chidamide	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
Chidamide combined with VDDT regimen	Vinorelbine	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
Chidamide combined with VDDT regimen	Thalidomide	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
Chidamide combined with VDDT regimen	Dexamethasone	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

Primary Outcome Measures

Name	Time	Method
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
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
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.

Secondary Outcome Measures

Name	Time	Method
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.
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

Trial Locations

Locations (1)

Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university; 🇨🇳 ZhengZhou, Henan, China