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R-Dose-adjusted (DA) - EPOCH-21 Versus R-modified Non-Hodgkin Lymphoma (NHL)-Berlin-Frankfurt-Munster (BFM)-90 Program (mNHL-BFM-90) and Autologous Stem Cells Transplantation (Auto-SCT) in DLBCL With Poor Prognosis

Primary Purpose

Diffuse Large B-Cell Lymphoma

Status
Unknown status
Phase
Phase 3
Locations
Russian Federation
Study Type
Interventional
Intervention
R-DA-EPOCH-21
R-DA-EPOCH-21 + auto-SCT
R-mNHL-BFM-90
R-mNHL-BFM-90 + auto-SCT
Sponsored by
National Research Center for Hematology, Russia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B-Cell Lymphoma focused on measuring DLBCL, R-DA-EPOCH-21, R-mNHL-BFM-90, auto-SCT

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Newly diagnosed DLBCL,
  2. No previous treatment with chemotherapy and/or radiation therapy of DLBCL
  3. Presence of 2 or more signs of unfavorable prognosis (IPI 2-4)
  4. Age 18-60 years.

Exclusion Criteria:

  1. Transformation of mature cell lymphomas in DLBCL.
  2. B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Hodgkin's lymphoma
  3. B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma
  4. DLBCL of central nervous system (CNS)
  5. testicular DLBCL
  6. Primary mediastinal large B-cell lymphoma
  7. Pretreated DLBCL.
  8. HIV-associated DLBCL
  9. Congestive heart failure, unstable angina, severe cardiac arrhythmias and conduction disturbances, myocardial infarction.
  10. Renal insufficiency (serum creatinine greater than 0.2 mmol/L) (except cases with specific kidney infiltration, urinary tract compression by tumor conglomerate or presence of uric acid nephropathy due to massive cytolysis syndrome).
  11. Liver failure (except cases with liver tumor infiltration), acute hepatitis or active phase of chronic hepatitis B or C with serum bilirubin greater than 1.5 standards, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) greater than 3 standards, prothrombin index less than 70%.
  12. Severe pneumonia (except cases with specific lungs infiltration), accompanied by respiratory failure (dyspnea > 30 in min., hypoxemia less than 70 mm Hg, when it is impossible to compensate situation in 2-3 days).
  13. Life-threatening bleeding (gastrointestinal, intracranial), with exception of bleeding due to tumor infiltration of organs (stomach, intestines, uterus, etc.) and disseminated intravascular coagulation due to underlying disease complications after their successful conservative treatment.
  14. Severe mental disorders (delusions, severe depressive syndrome and other manifestations of productive symptoms) not related with specific infiltration of central nervous system.
  15. Decompensated diabetes.
  16. Pregnancy.

Sites / Locations

  • National Research Center for HematologyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

R-DA-EPOCH-21

R-DA-EPOCH-21 + auto-SCT

R-mNHL-BFM-90

R-mNHL-BFM-90 + auto-SCT

Arm Description

Protocol involves 6 cycles.

Protocol involves 6 cycles. Patients with complete remission undergo auto-SCT after 6 cycles and patients with partial remission after 6 cycles undergo auto-SCT after 2 cycles of R-DHAP

Course A: Rituximab 375 mg/m2 IV 0 day, Dexamethasone 10 mg/m2/day IV 1 - 5 days, Methotrexate 1000 mg/m2 12 h IV 1 day, Ifosfamide 800 mg/m2/day 1 h IV 1 - 5 days, Etoposide 100 mg/m2/day IV 4, 5 days, Doxorubicin 25 mg/m2/day IV 1, 2 days, Vincristine 2 mg IV 1 day, Cytarabine 100 mg/m2/day IV 1 h 4, 5 days. Course B: Rituximab 375 mg/m2 IV 0 day, Dexamethasone 10 mg/m2/day IV 1 - 5 days, Cyclophosphamide 200 mg/m2/day IV 1 h 1 - 5 days, Methotrexate 1000 mg/m2 12 h IV 1 day, Doxorubicin 25 mg/m2/day IV 4, 5 days, Vincristine 2 mg IV 1 day. Protocol involves 6 cycles : A-B-A-B-A-B. One cycle continues 21 days.

Protocol involves 6 cycles R-mNHL-BFM-90: A-B-A-B-A-B. Patients with complete remission undergo auto-SCT after 6 cycles and patients with partial remission after 6 cycles undergo auto-SCT after 2 cycles of R-DHAP

Outcomes

Primary Outcome Measures

complete response
(physical examination, standard blood tests, including assessment of LDH level, thoracic and abdominal computerized tomography (together with any other anatomic site, as clinically indicated), bone marrow biopsy in case of bone marrow involvement and 18F-fludeoxyglucose positron emission tomography (18FDG-PET) (not mandatory) in case of residual measurable disease at the end of the chemoimmunotherapy).

Secondary Outcome Measures

overall survival
Survival time and time to disease progression are calculated in months from day of enrollment in the study until death, relapse, progression, or last follow-up, as appropriate
disease-free survival
Survival time and time to disease progression are calculated in months from day of enrollment in the study until death, relapse, progression, or last follow-up, as appropriate
event-free survival
Survival time and time to disease progression are calculated in months from day of enrollment in the study until death, relapse, progression, or last follow-up, as appropriate

Full Information

First Posted
March 11, 2016
Last Updated
July 20, 2016
Sponsor
National Research Center for Hematology, Russia
Collaborators
National Research Center for Hematology
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1. Study Identification

Unique Protocol Identification Number
NCT02842931
Brief Title
R-Dose-adjusted (DA) - EPOCH-21 Versus R-modified Non-Hodgkin Lymphoma (NHL)-Berlin-Frankfurt-Munster (BFM)-90 Program (mNHL-BFM-90) and Autologous Stem Cells Transplantation (Auto-SCT) in DLBCL With Poor Prognosis
Official Title
Multicenter, Randomized, Controlled (Comparative), Open, Prospective Study Evaluating an Efficacy of R-DA-EPOCH-21, R-mNHL-BFM-90 and (Auto-SCT)in Patients With DLBCL
Study Type
Interventional

2. Study Status

Record Verification Date
July 2016
Overall Recruitment Status
Unknown status
Study Start Date
February 2015 (undefined)
Primary Completion Date
February 2020 (Anticipated)
Study Completion Date
February 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Research Center for Hematology, Russia
Collaborators
National Research Center for Hematology

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Purpose: to evaluate an efficacy of chemotherapy regimens R-DA-EPOCH-21 and R-mNHL-BFM-90 with and without autologous hematopoietic stem cells transplantation (auto-SCT) in newly diagnosed patients with DLBCL with intermediate and high risk.
Detailed Description
Patients initially are randomized into 4 arms: st arm R-DA-EPOCH-21 nd arm R-mNHL-BFM-90 rd arm R-DA-EPOCH-21 + auto-SCT th arm of R-mNHL-BFM-90 + auto-SCT Patients who achieved complete remission after 6 cycles of R-DA-EPOCH-21 or R-mNHL-BFM-90 immunochemotherapy continue to be under observation (1st and 2nd arms) or continue treatment with Rituximab + BCNU+Etoposid+Ara-C+Melphalan (R-BEAM) followed by auto-SCT (3rd and 4th arms). Patients who achieved partial remission after 6 cycles of R-DA-EPOCH-21 or R-mNHL-BFM-90 immunochemotherapy continue treatment with 2 cycles of Rituximab+Dexamethasone+Ara-C+Cisplatin (R-DHAP), continue to be under observation (1st and 2nd arms) or continue treatment with R-BEAM, followed by auto-SCT (3rd and 4th arms).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-Cell Lymphoma
Keywords
DLBCL, R-DA-EPOCH-21, R-mNHL-BFM-90, auto-SCT

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
R-DA-EPOCH-21
Arm Type
Active Comparator
Arm Description
Protocol involves 6 cycles.
Arm Title
R-DA-EPOCH-21 + auto-SCT
Arm Type
Active Comparator
Arm Description
Protocol involves 6 cycles. Patients with complete remission undergo auto-SCT after 6 cycles and patients with partial remission after 6 cycles undergo auto-SCT after 2 cycles of R-DHAP
Arm Title
R-mNHL-BFM-90
Arm Type
Active Comparator
Arm Description
Course A: Rituximab 375 mg/m2 IV 0 day, Dexamethasone 10 mg/m2/day IV 1 - 5 days, Methotrexate 1000 mg/m2 12 h IV 1 day, Ifosfamide 800 mg/m2/day 1 h IV 1 - 5 days, Etoposide 100 mg/m2/day IV 4, 5 days, Doxorubicin 25 mg/m2/day IV 1, 2 days, Vincristine 2 mg IV 1 day, Cytarabine 100 mg/m2/day IV 1 h 4, 5 days. Course B: Rituximab 375 mg/m2 IV 0 day, Dexamethasone 10 mg/m2/day IV 1 - 5 days, Cyclophosphamide 200 mg/m2/day IV 1 h 1 - 5 days, Methotrexate 1000 mg/m2 12 h IV 1 day, Doxorubicin 25 mg/m2/day IV 4, 5 days, Vincristine 2 mg IV 1 day. Protocol involves 6 cycles : A-B-A-B-A-B. One cycle continues 21 days.
Arm Title
R-mNHL-BFM-90 + auto-SCT
Arm Type
Active Comparator
Arm Description
Protocol involves 6 cycles R-mNHL-BFM-90: A-B-A-B-A-B. Patients with complete remission undergo auto-SCT after 6 cycles and patients with partial remission after 6 cycles undergo auto-SCT after 2 cycles of R-DHAP
Intervention Type
Drug
Intervention Name(s)
R-DA-EPOCH-21
Intervention Description
R-DA-EPOCH-21 treatment without auto-SCT for DLBCL patients younger than 60 years with intermediate and high risk for IPI
Intervention Type
Drug
Intervention Name(s)
R-DA-EPOCH-21 + auto-SCT
Intervention Description
R-DA-EPOCH-21 treatment with auto-SCT for DLBCL patients younger than 60 years with intermediate and high risk for IPI
Intervention Type
Drug
Intervention Name(s)
R-mNHL-BFM-90
Intervention Description
R-mNHL-BFM-90 without auto-SCT in patients with DLBCL under the age of 60 years with intermediate and high risk for IPI
Intervention Type
Drug
Intervention Name(s)
R-mNHL-BFM-90 + auto-SCT
Intervention Description
R-mNHL-BFM-90 with auto-SCT in patients with DLBCL under the age of 60 years with intermediate and high risk for IPI
Primary Outcome Measure Information:
Title
complete response
Description
(physical examination, standard blood tests, including assessment of LDH level, thoracic and abdominal computerized tomography (together with any other anatomic site, as clinically indicated), bone marrow biopsy in case of bone marrow involvement and 18F-fludeoxyglucose positron emission tomography (18FDG-PET) (not mandatory) in case of residual measurable disease at the end of the chemoimmunotherapy).
Time Frame
168 day
Secondary Outcome Measure Information:
Title
overall survival
Description
Survival time and time to disease progression are calculated in months from day of enrollment in the study until death, relapse, progression, or last follow-up, as appropriate
Time Frame
Five-year survival
Title
disease-free survival
Description
Survival time and time to disease progression are calculated in months from day of enrollment in the study until death, relapse, progression, or last follow-up, as appropriate
Time Frame
Five-year survival
Title
event-free survival
Description
Survival time and time to disease progression are calculated in months from day of enrollment in the study until death, relapse, progression, or last follow-up, as appropriate
Time Frame
Five-year survival

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Newly diagnosed DLBCL, No previous treatment with chemotherapy and/or radiation therapy of DLBCL Presence of 2 or more signs of unfavorable prognosis (IPI 2-4) Age 18-60 years. Exclusion Criteria: Transformation of mature cell lymphomas in DLBCL. B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Hodgkin's lymphoma B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma DLBCL of central nervous system (CNS) testicular DLBCL Primary mediastinal large B-cell lymphoma Pretreated DLBCL. HIV-associated DLBCL Congestive heart failure, unstable angina, severe cardiac arrhythmias and conduction disturbances, myocardial infarction. Renal insufficiency (serum creatinine greater than 0.2 mmol/L) (except cases with specific kidney infiltration, urinary tract compression by tumor conglomerate or presence of uric acid nephropathy due to massive cytolysis syndrome). Liver failure (except cases with liver tumor infiltration), acute hepatitis or active phase of chronic hepatitis B or C with serum bilirubin greater than 1.5 standards, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) greater than 3 standards, prothrombin index less than 70%. Severe pneumonia (except cases with specific lungs infiltration), accompanied by respiratory failure (dyspnea > 30 in min., hypoxemia less than 70 mm Hg, when it is impossible to compensate situation in 2-3 days). Life-threatening bleeding (gastrointestinal, intracranial), with exception of bleeding due to tumor infiltration of organs (stomach, intestines, uterus, etc.) and disseminated intravascular coagulation due to underlying disease complications after their successful conservative treatment. Severe mental disorders (delusions, severe depressive syndrome and other manifestations of productive symptoms) not related with specific infiltration of central nervous system. Decompensated diabetes. Pregnancy.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Aminat Magomedova, MD, PhD
Phone
495-613-2446
Ext
007
Email
maminat@mail.ru
First Name & Middle Initial & Last Name or Official Title & Degree
Sergay Kravchenko, MD PhD
Phone
495-613-2446
Ext
007
Email
krav-hsc-ramn@mail.ru
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elena N Parovichnikova, MD PhD
Organizational Affiliation
National Research Center for Hematology, Russia
Official's Role
Study Chair
Facility Information:
Facility Name
National Research Center for Hematology
City
Moscow
ZIP/Postal Code
125167
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aminat U Magomedova, MD, PhD
Phone
495-613-2446
Ext
007
Email
maminat@mail.ru
First Name & Middle Initial & Last Name & Degree
Sergay K Kravchenko, MD, PhD
Phone
495-613-2446
Ext
007
Email
krav-hsc-ramn@mail.ru
First Name & Middle Initial & Last Name & Degree
Aminat U Magomedova, MD, PhD
First Name & Middle Initial & Last Name & Degree
Sergey K Kravchenko, MD, PhD
First Name & Middle Initial & Last Name & Degree
Anna E Misurina, MD, PhD

12. IPD Sharing Statement

Learn more about this trial

R-Dose-adjusted (DA) - EPOCH-21 Versus R-modified Non-Hodgkin Lymphoma (NHL)-Berlin-Frankfurt-Munster (BFM)-90 Program (mNHL-BFM-90) and Autologous Stem Cells Transplantation (Auto-SCT) in DLBCL With Poor Prognosis

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