A Prospective Study of Low-dose Decitabine Combined With COP Regimen in the Treatment of Relapsed and Refractory DLBCL

NCT ID: NCT03494296

Last Updated: 2018-04-11

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 150 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-03-01
• Study Completion Date: 2026-12-31

Brief Summary

Decitabine is a cytosine analogue and is a specific DNA methyltransferase (DNMT) inhibitor. It directly inhibits DNMT by phosphorylating DNA and inhibits DNMT, thereby reversing DNA methylation and inducing tumor cells to Normal cell differentiation or induction of tumor cell apoptosis.Diffuse large B-cell lymphoma (DLBCL) is the most common pathological type in non-Hodgkin's lymphoma. The first-line chemotherapy regimen using Rituximab+Cyclophosphamide+Doxorubicin +Vincristine+Bonisone（R-CHOP）significantly increases the remission rate and disease-free survival of patients with DLBCL, but it is difficult to partially relapse. Long-term remission and survival rates in treating patients are not satisfactory.Due to the greater cardiac toxicity of adriamycin, more patients can not be uncomfortable, so the COP program is also widely used in patients with DLBCL, and achieved a good response rate.In 2008, the FDA had approved decitabine for the demethylation treatment of Myelodysplastic syndrome（MDS）. Over the years, good initial remission rates and better long-term survival rates have been achieved in patients with MDS.There are also a variety of clinical trials of decitabine for patients with solid tumors that have achieved significant clinical efficacy.Due to the high side effects of high-dose decitabine, patient tolerance is poor. Therefore, the purpose of this study was to evaluate the efficacy and safety of low-dose decitabine combined with Cyclophosphamide+Vindesine+Bonisone(COP) regimen (D-COP) 4-6 course of treatment for relapsed and refractory diffuse large B-cell lymphoma.

Detailed Description

Decitabine is a cytosine analogue and is a specific DNA methyltransferase (DNMT) inhibitor. It directly inhibits DNMT by phosphorylating DNA and inhibits DNMT, thereby reversing DNA methylation and inducing tumor cells to Normal cell differentiation or induction of tumor cell apoptosis. High concentrations of decitabine inhibit DNA synthesis, exert its cytotoxic effects, and induce cell death; low concentrations of decitabine inactivate DNMT and demethylate some hypermethylated CpG islands in tumor suppressor genes. To activate the silencing tumor suppressor gene and exert its effect of inhibiting tumor growth to achieve anti-tumor effects.

Epigenetics plays an important role in the occurrence and development of tumors and is a hot topic in recent years. Methylation of DNA is the main form of epigenetic information. Normal methylation plays an important role in maintaining the normal functions of cells and organs and in the development, differentiation, growth, and aging of the body. However, the abnormal participation of cell epigenetics can directly affect the overexpression of tumor cells, which leads to the occurrence and development of tumor cells.

Diffuse large B-cell lymphoma (DLBCL) is the most common pathological type in non-Hodgkin's lymphoma. The first-line chemotherapy regimen using R-CHOP significantly increases the remission rate and disease-free survival of patients with DLBCL, but it is difficult to partially relapse. Long-term remission and survival rates in treating patients are not satisfactory.Due to the greater cardiac toxicity of adriamycin, more patients can not be uncomfortable, so the COP program is also widely used in patients with DLBCL, and achieved a good response rate.In 2008, the FDA had approved decitabine for the demethylation treatment of MDS. Over the years, good initial remission rates and better long-term survival rates have been achieved in patients with MDS.There are also a variety of clinical trials of decitabine for patients with solid tumors that have achieved significant clinical efficacy.Due to the high side effects of high-dose decitabine, patient tolerance is poor. Therefore, the purpose of this study was to evaluate the efficacy and safety of low-dose decitabine combined with COP regimen (D-COP) 4-6 course of treatment for relapsed and refractory diffuse large B-cell lymphoma.

In summary, this study will select relapsed refractory high-risk patients, previous studies have confirmed that the COP program can make a good effect in most patients, also confirmed the demethylation of decitabine in other tumors Therefore, whether the treatment of low-dose decitabine combined with COP regimen for DLBCL can improve the prognosis is worth looking forward to. At present, there are few researches on the treatment of DLBCL with low-dose decitabine at home and abroad. The purpose of this study is to explore whether low-dose decitabine combined with COP regimen as a treatment for patients with relapsed and refractory DLBCL can improve the relapse-refractory DLBCL. The patient's prognosis, and hope to explore through a stratified analysis which group of patients benefit more from it.

Conditions

Lymphoma

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Open, multi-center, prospective

All enrolled and relapsed patients received D-COP regimen chemotherapy

patients received D-COP regimen chemotherapy

Intervention Type: DRUG

patients received D-COP regimen chemotherapy

Interventions

patients received D-COP regimen chemotherapy

patients received D-COP regimen chemotherapy

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Histopathology confirmed as DLBCL.

2. Relapsed and refractory patients.

3. Age ≥ 18 years old.

4. ECOG ≥ 3.

5. Women are not lactating, not pregnant, and agree not to become pregnant during the study period and within the next 12 months. Male patients agree that their spouse is not pregnant during the study period and within the next 12 months。

6. There is an assessable lesion (lymph node diameter ≥ 1.0cm; or a dermatologic lesion that can be assessed by a physical examination)Signed informed consent

Exclusion Criteria

1. Bone marrow involvement and lymphoma cells ≥ 25%.

2. Severe abnormal liver and kidney function (alanine aminotransferase, bilirubin, creatinine> 3 times the upper limit of normal).

3. Uncontrolled active infections.

4. Organic heart disease and clinical symptoms or abnormal heart function (NYHA ≥ 2).

5. Simultaneous presence of other tumors.

6. Other psychological conditions that prevent patients from participating in the study or signing informed consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First Affiliated Hospital of Harbin Medical University

OTHER

Sponsor Role: lead

Responsible Party

Shuye Wang

Director of the lymphoma ward

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shuye Wang, PhD

Role: STUDY_CHAIR

First Affiliated Hospital of Harbin Medical University

Locations

The First Affiliated Hospital of Harbin Medical University, Department of Hematology, Lymphoma Ward

Harbin, Heilongjiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Qi Zhou, Master

Role: CONTACT

kykbgs123@163.com

0451-85552320

Facility Contacts

Shuye Wang, PhD

Role: primary

wsywangshuye@126.com

0451-85552226

Other Identifiers

Organization:FirstAHHarbinMU

Identifier Type: -

Identifier Source: org_study_id