Diffuse Large B-cell Lymphoma
Conditions
Keywords
Diffuse Large B-Cell Lymphoma, Relapsed and refractory, Histone deacetylase inhibitor, Chidamide
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.
Interventions
DRUGChidamide
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
DRUGVinorelbine
20mg/m2， IV on day 1 of each 14 day cycle until disease progression or unacceptable toxicity develops, up to 12 cycles
DRUGLiposomal 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
DRUGDexamethasone
10mg/m2 , IV on day 1-5 of each 14 day cycle until disease progression or unacceptable toxicity develops, up to 12 cycles
DRUGThalidomide
100mg,Oral at night on each day until disease progression or unacceptable toxicity develops, up to 24 weeks
Sponsors
Henan Cancer Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
China
Contacts
Primary ContactYanyan Liu, M.D. Ph.D
Backup ContactJiuyang Zhang, Master
Outcome results
None listed