出境医 / 临床实验 / A Prospective Study of Low-dose Decitabine Combined With COP Regimen in the Treatment of Relapsed and Refractory DLBCL

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

Study Description
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.

Condition or disease Intervention/treatment
Lymphoma Drug: patients received D-COP regimen chemotherapy

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 Design
Layout table for study information
Study Type : Observational
Estimated Enrollment : 150 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: A Prospective Study of Low-dose Decitabine Combined With COP Regimen in the Treatment of Relapsed and Refractory DLBCL
Actual Study Start Date : March 1, 2018
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2026
Arms and Interventions
Group/Cohort Intervention/treatment
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

Outcome Measures
Primary Outcome Measures :
  1. 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.



Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Plans to enroll 150 cases within 2 years
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
Contacts and Locations

Contacts
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Contact: Qi Zhou, Master 0451-85552320 kykbgs123@163.com

Locations
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China, Heilongjiang
The First Affiliated Hospital of Harbin Medical University, Department of Hematology, Lymphoma Ward Recruiting
Harbin, Heilongjiang, China, 150001
Contact: Shuye Wang, PhD    0451-85552226    wsywangshuye@126.com   
Sponsors and Collaborators
First Affiliated Hospital of Harbin Medical University
Investigators
Layout table for investigator information
Study Chair: Shuye Wang, PhD First Affiliated Hospital of Harbin Medical University

Tracking Information
First Submitted Date March 19, 2018
First Posted Date April 11, 2018
Last Update Posted Date April 11, 2018
Actual Study Start Date March 1, 2018
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: April 10, 2018)
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.
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title A Prospective Study of Low-dose Decitabine Combined With COP Regimen in the Treatment of Relapsed and Refractory DLBCL
Official Title A Prospective Study of Low-dose Decitabine Combined With COP Regimen in the Treatment of Relapsed and Refractory DLBCL
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.

Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Plans to enroll 150 cases within 2 years
Condition Lymphoma
Intervention Drug: patients received D-COP regimen chemotherapy
patients received D-COP regimen chemotherapy
Study Groups/Cohorts Open, multi-center, prospective
All enrolled and relapsed patients received D-COP regimen chemotherapy
Intervention: Drug: patients received D-COP regimen chemotherapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: April 10, 2018)
150
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 31, 2026
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Qi Zhou, Master 0451-85552320 kykbgs123@163.com
Listed Location Countries China
Removed Location Countries  
 
Administrative Information
NCT Number NCT03494296
Other Study ID Numbers Organization:FirstAHHarbinMU
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Shuye Wang, First Affiliated Hospital of Harbin Medical University
Study Sponsor First Affiliated Hospital of Harbin Medical University
Collaborators Not Provided
Investigators
Study Chair: Shuye Wang, PhD First Affiliated Hospital of Harbin Medical University
PRS Account First Affiliated Hospital of Harbin Medical University
Verification Date April 2018

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