Back to resultsR-BL-M-04 Versus R-(DA)-EPOCH and Autologous Stem Cells Transplantation in Patients With High-Grade B-cell Lymphoma Double-hit (HGBL DH) and High-Grade B-cell Lymphoma Not Otherwise Specified (HGBL NOS)
Primary Purpose
Lymphoma, High-Grade
Status
Recruiting
Phase
Phase 3
Locations
Russian Federation
Study Type
Interventional
Intervention
R-DA-EPOCH-21
R-BL-M-04
R-DA-EPOCH-21 + auto-SCT
R-BL-M-04 + auto-SCT
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma, High-Grade
Eligibility Criteria
Inclusion Criteria:
- First established the diagnosis of HGBL DH or HGBL-NOS.
- No previous treatment with chemotherapy and/or radiation therapy of DLBCL
- Informed consent of the patient.
Exclusion Criteria:
- Pretreated lymphoma.
- HIV-associated lymphoma
- 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 tumour conglomerate or presence of uric acid nephropathy due to massive cytolysis syndrome).
- Liver failure (except cases with liver tumour 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 tumour 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 to specific infiltration of a central nervous system.
- Decompensated diabetes.
11. 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-BL-M-04
R-DA-EPOCH-21 + auto-SCT
R-BL-M-04 + auto-SCT
Arm Description
The protocol involves 4-6 cycles. Intrathecal administration of dexamethasone 4 mg, methotrexate 15 mg and cytarabine 30 mg is required once during chemotherapy. In case of CNS involvement intrathecal administration is repeated 3 times a week till the normal cell count in cerebrospinal liquid.
Course A: Rituximab 375 mg/m2 IV 0 day, Dexamethasone 10 mg/m2/day IV 1 - 5 days, Methotrexate 1500 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 50 mg/m2/day IV day 3, Vincristine 2 mg IV 1 day, Cytarabine 150 mg/m2/day IV 1 h 4, 5 days. Course C: Rituximab 375 mg/m2 IV 0 day, Dexamethasone 10 mg/m2/day IV 1 - 5 days, Methotrexate 1500 mg/m2 12 h IV 1 day, Vinblastine 5 mg/m2 IV day 1, Cytarabine 2000 mg/m2/day IV 3 h 2, 3 days, Etoposide 150 mg/m2/day IV 3-5 days. Intrathecal administration of dexamethasone 4 mg, methotrexate 15 mg and cytarabine 30 mg is required once during chemotherapy. In case of CNS involvement intrathecal administration is repeated 3 times a week till the normal cell count in cerebrospinal liquid.
The protocol involves 4-6 cycles. Patients with complete remission after 4 cycles undergo auto-SCT. Intrathecal administration of dexamethasone 4 mg, methotrexate 15 mg and cytarabine 30 mg is required once during chemotherapy. In case of CNS involvement intrathecal administration is repeated 3 times a week till the normal cell count in cerebrospinal liquid.
The protocol involves 4 cycles. Patients with complete remission after 4 cycles undergo auto-SCT. Intrathecal administration of dexamethasone 4 mg, methotrexate 15 mg and cytarabine 30 mg is required once during chemotherapy. In case of CNS involvement intrathecal administration is repeated 3 times a week till the normal cell count in cerebrospinal liquid.
Outcomes
Primary Outcome Measures
Overall survival
Overall survival
Relapse-free survival
Relapse-free survival
Progression
Frequency of progression
Secondary Outcome Measures
Complete remission
Frequency of complete remission
Partial remission
Frequency of partial remission
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03479918
Brief Title
R-BL-M-04 Versus R-(DA)-EPOCH and Autologous Stem Cells Transplantation in Patients With High-Grade B-cell Lymphoma Double-hit (HGBL DH) and High-Grade B-cell Lymphoma Not Otherwise Specified (HGBL NOS)
Official Title
Randomized, Controlled (Comparative), Open, Prospective Study Evaluating an Efficacy of R-DA-EPOCH-21, R-BL-M-04 and Autologous Stem Cells Transplantation in Patients With High-Grade B-cell Lymphoma Double-hit and High-Grade B-cell Lymphoma Not Otherwise Specified
Study Type
Interventional
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Recruiting
Study Start Date
March 15, 2018 (Actual)
Primary Completion Date
March 15, 2021 (Anticipated)
Study Completion Date
March 15, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Elena N.Parovichnikova
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Purpose: to evaluate an efficacy of chemotherapy regimens R-DA-EPOCH-21 and R-BL-04 with and without autologous hematopoietic stem cells transplantation (auto-SCT) in newly diagnosed patients with High-Grade B-cell Lymphoma Double-hit and High-Grade B-cell Lymphoma Not Otherwise Specified.
Detailed Description
Patients initially are randomized into 4 arms:
the first arm R-DA-EPOCH-21 the second arm R-BL-M-04 the third arm R-DA-EPOCH-21 + auto-SCT the fourth arm of R-BL-M-04 + auto-SCT Patients who achieved complete remission after 6 cycles of R-DA-EPOCH-21 or 4 cycles of R-BL-M-04 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 did not achieve complete remission with PET-CT data (4-5 Deauville points) are removed from the protocol and undergoing second-line therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, High-Grade
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Factorial Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
R-DA-EPOCH-21
Arm Type
Active Comparator
Arm Description
The protocol involves 4-6 cycles. Intrathecal administration of dexamethasone 4 mg, methotrexate 15 mg and cytarabine 30 mg is required once during chemotherapy. In case of CNS involvement intrathecal administration is repeated 3 times a week till the normal cell count in cerebrospinal liquid.
Arm Title
R-BL-M-04
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 1500 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 50 mg/m2/day IV day 3, Vincristine 2 mg IV 1 day, Cytarabine 150 mg/m2/day IV 1 h 4, 5 days.
Course C:
Rituximab 375 mg/m2 IV 0 day, Dexamethasone 10 mg/m2/day IV 1 - 5 days, Methotrexate 1500 mg/m2 12 h IV 1 day, Vinblastine 5 mg/m2 IV day 1, Cytarabine 2000 mg/m2/day IV 3 h 2, 3 days, Etoposide 150 mg/m2/day IV 3-5 days.
Intrathecal administration of dexamethasone 4 mg, methotrexate 15 mg and cytarabine 30 mg is required once during chemotherapy. In case of CNS involvement intrathecal administration is repeated 3 times a week till the normal cell count in cerebrospinal liquid.
Arm Title
R-DA-EPOCH-21 + auto-SCT
Arm Type
Active Comparator
Arm Description
The protocol involves 4-6 cycles. Patients with complete remission after 4 cycles undergo auto-SCT.
Intrathecal administration of dexamethasone 4 mg, methotrexate 15 mg and cytarabine 30 mg is required once during chemotherapy. In case of CNS involvement intrathecal administration is repeated 3 times a week till the normal cell count in cerebrospinal liquid.
Arm Title
R-BL-M-04 + auto-SCT
Arm Type
Active Comparator
Arm Description
The protocol involves 4 cycles. Patients with complete remission after 4 cycles undergo auto-SCT.
Intrathecal administration of dexamethasone 4 mg, methotrexate 15 mg and cytarabine 30 mg is required once during chemotherapy. In case of CNS involvement intrathecal administration is repeated 3 times a week till the normal cell count in cerebrospinal liquid.
Intervention Type
Drug
Intervention Name(s)
R-DA-EPOCH-21
Other Intervention Name(s)
R-DA-EPOCH
Intervention Description
R-DA-EPOCH-21 treatment without auto-SCT for HGBL DH and HGBL NOS patients younger than 60 years. Courses are repeated every 21 days.
Intervention Type
Drug
Intervention Name(s)
R-BL-M-04
Intervention Description
R-BL-M-04 treatment without auto-SCT for HGBL DH and HGBL NOS patients younger than 60 years. Courses are repeated every 21 days.
Intervention Type
Drug
Intervention Name(s)
R-DA-EPOCH-21 + auto-SCT
Other Intervention Name(s)
R-DA-EPOCH + auto-SCT
Intervention Description
R-DA-EPOCH-21 treatment with auto-SCT for HGBL DH and HGBL NOS patients younger than 60 years. Courses are repeated every 21 days.
Intervention Type
Drug
Intervention Name(s)
R-BL-M-04 + auto-SCT
Intervention Description
R-BL-M-04 treatment with auto-SCT for HGBL DH and HGBL NOS patients younger than 60 years. Courses are repeated every 21 days.
Primary Outcome Measure Information:
Title
Overall survival
Description
Overall survival
Time Frame
2 years
Title
Relapse-free survival
Description
Relapse-free survival
Time Frame
2 years
Title
Progression
Description
Frequency of progression
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Complete remission
Description
Frequency of complete remission
Time Frame
1 year
Title
Partial remission
Description
Frequency of partial remission
Time Frame
1 year
Other Pre-specified Outcome Measures:
Title
Probability of relapse or progression
Description
Probability of relapse or progression
Time Frame
2 years
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:
First established the diagnosis of HGBL DH or HGBL-NOS.
No previous treatment with chemotherapy and/or radiation therapy of DLBCL
Informed consent of the patient.
Exclusion Criteria:
Pretreated lymphoma.
HIV-associated lymphoma
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 tumour conglomerate or presence of uric acid nephropathy due to massive cytolysis syndrome).
Liver failure (except cases with liver tumour 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 tumour 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 to specific infiltration of a central nervous system.
Decompensated diabetes.
11. Pregnancy.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anna Misyurina, PhD
Phone
9096373249
Email
anna.lukina1@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Sergey Kravchenko, PhD
Phone
+74956132446
Email
krav-hsc-ramn@mail.ru
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elena Parovichnokva, PhD
Organizational Affiliation
National Research Center for Hematology, Moscow, Russian Federation
Official's Role
Principal Investigator
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
Elena Parovichnikova, MD, PhD
Email
director@blood.ru
First Name & Middle Initial & Last Name & Degree
Sergey Kravchenko, MD, PhD
First Name & Middle Initial & Last Name & Degree
Anna Misyurina, MD, PhD
First Name & Middle Initial & Last Name & Degree
Aminat Magomedova, MD, PhD
First Name & Middle Initial & Last Name & Degree
Sergey Kulikov, PhD
First Name & Middle Initial & Last Name & Degree
Alla Kovrigina, PhD
First Name & Middle Initial & Last Name & Degree
Tatiana Obukhova, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
R-BL-M-04 Versus R-(DA)-EPOCH and Autologous Stem Cells Transplantation in Patients With High-Grade B-cell Lymphoma Double-hit (HGBL DH) and High-Grade B-cell Lymphoma Not Otherwise Specified (HGBL NOS)
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