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)

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Lymphoma, High-Grade

Intervention / Treatment
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* Drug: R-DA-EPOCH-21
* Drug: R-BL-M-04
* Drug: R-DA-EPOCH-21 + auto-SCT
* Drug: R-BL-M-04 + auto-SCT


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: R-DA-EPOCH-21<br>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. | Drug: R-DA-EPOCH-21<br>* 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.<br>* Other names: R-DA-EPOCH;|
| Active Comparator: R-BL-M-04<br>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. | Drug: R-BL-M-04<br>* 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.<br>|
| Active Comparator: R-DA-EPOCH-21 + auto-SCT<br>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. | Drug: R-DA-EPOCH-21 + auto-SCT<br>* 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.<br>* Other names: R-DA-EPOCH + auto-SCT;|
| Active Comparator: R-BL-M-04 + auto-SCT<br>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. | Drug: R-BL-M-04 + auto-SCT<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival | 2 years | 
| Relapse-free survival | Relapse-free survival | 2 years | 
| Progression | Frequency of progression | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission | Frequency of complete remission | 1 year | 
| Partial remission | Frequency of partial remission | 1 year |