Clinical trial NCT03373019: Chidamide Combined With R-GDP in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)
Official title: A Non-randomized, Open-label, Phase II Study of Chidamide Combined With R-GDP in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL) Not Suitable for Transplantation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Chidamide
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasm by Histology
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Rituximab
Gemcitabine
Cisplatin
Dexamethasone
HDAC Inhibitor
Keywords: chidamide
R-GDP
diffuse large B-cell lymphoma
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2017-12-14
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to evaluate therapeutic efficacy of Chidamide combined with R-GDP （rituximab/gemcitabine/dexamethasone/cisplatin）in treating Patients with relapsed or refractory Diffuse Large B-cell Lymphoma (DLBCL) not suitable for transplantation.

Detailed description: The treatment outcome of patients with relapsed or refractory Diffuse Large B-cell Lymphoma (DLBCL) are not satisfactory especially for those not suitable for transplantation. One of main reason is chemotherapy resistance. The investigators conducted this study to evaluate the efficacy of Chidamide combined with R-GDP(rituximab/gemcitabine/dexamethasone/cisplatin) in treating patients with relapsed or refractory Diffuse Large B-cell Lymphoma (DLBCL) not suitable for transplantation. Chidamide is a novel benzamide type of subtype-selective histone deacetylase (HDAC) inhibitor. It has been approved by China Food and Drug Administration (CFDA) for treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL) in Chinese population. The investigators' pre-clinical data suggested that this agent might be also efficient in the treatment of relapsed/refractory B cell lymphoma. In this open-label, non-randomized, phase II study, the investigators aimed to observe the efficacy and safety of chidamide combined with R-GDP in patients with relapsed or refractory Diffuse Large B-cell Lymphoma (DLBCL) not suitable for transplantation.

Eligibility criteria: Inclusion Criteria:

1. Ages: 18-75 years old
2. Relapsed or refractory Diffuse Large B-cell Lymphoma (DLBCL) previous treated with standard chemoimmunotherapy
3. Not willing or not suitable for hematopoietic stem cell transplantation (HSCT)
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) index \< 2
5. Informed consent available
6. Life expectancy of more than 3 months;
7. Ultrasonic cardiogram showed left ventricle ejection fraction ≥ 50%, EKG showed on signs of myocardial ischemia, with no previous arrhythmia which need pharmacological intervention.
8. Bone marrow function: ANC ≥ 1.5 × 109/L, PLT ≥ 100 × 109/L, Hb ≥ 80g/L;
9. Liver function: total bilirubin, ALT and AST were \<1.5 × UNL (the upper limit of normal value)
10. Renal function: Cr\<1.5 × UNL and creatinine clearance \> 50ml/min

Exclusion Criteria:

1. Prior history of treatment of HDAC inhibitor.
2. Plan of HSCT in the future
3. Significant pericardial effusion showed by chest CT scan
4. Prior history of other cancers except treated cervical or basal cell skin carcinoma, organ transplantation
5. Syphilis or human immunodeficiency virus (HIV) infection
6. Pregnant or lactating women
7. History of organ transplantation
8. Serious active infections (including hepatitis)
9. Serious neurological or psychiatric history, including dementia or epilepsy.

Termination criteria:

1. Withdrew consent
2. Researchers think it is necessary to terminate the study;
3. Disease progression or death;
4. Poor compliance
5. Subclinical or clinical cardiac toxicity;
6. Unable to continue treatment because of severe toxicity

Primary outcomes:
measure: ORR
timeFrame: 6 weeks
Secondary outcomes:
measure: CR
timeFrame: 6 weeks
measure: OS
timeFrame: 3 years
measure: 3 year PFS
timeFrame: 3 years
measure: adverse event
timeFrame: throughout the treatment period，up to 6 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Kai Xue
state: Shanghai
city: Shanghai
country: China
facility: Kai Xue
Study officials:
References: