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

April 10, 2018 updated by: Shuye Wang, First Affiliated Hospital of Harbin Medical University
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
150

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150001
        • Recruiting
        • The First Affiliated Hospital of Harbin Medical University, Department of Hematology, Lymphoma Ward
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Plans to enroll 150 cases within 2 years

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Open, multi-center, prospective
All enrolled and relapsed patients received D-COP regimen chemotherapy
Drug: patients received D-COP regimen chemotherapy
patients received D-COP regimen chemotherapy

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
A Prospective Study of Low-dose Decitabine Combined With COP Regimen in the Treatment of Relapsed and Refractory DLBCL
Time Frame: From March 1, 2018 to December 31, 2020

Primary end point:

Using 5-year progression-free survival (PFS) as an index to evaluate the clinical effect of low-dose decitabine combined with COP chemotherapy.clinical efficacy of low-dose decitabine combined with COP regimen chemotherapy.

Efficacy assessment criteria:2007 revised standards for international lymphoma efficacy: J Clin Oncol 2007;25(5):579-586.
From March 1, 2018 to December 31, 2020

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
First Affiliated Hospital of Harbin Medical University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Shuye Wang, PhD, First Affiliated Hospital of Harbin Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2018

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2020

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 19, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 10, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 11, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 11, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 10, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2018

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Organization:FirstAHHarbinMU

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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