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)

Phase 3

• Conditions: Lymphoma, High-Grade
• Interventions: Drug: R-DA-EPOCH-21; Drug: R-BL-M-04; Drug: R-DA-EPOCH-21 + auto-SCT; Drug: R-BL-M-04 + auto-SCT

• Registration Number: NCT03479918
• Lead Sponsor: Elena N.Parovichnikova

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.

Study Timeline

• Status Verified: 2018-03
• Study Start: 2018-03-15
• Study First Submitted: 2018-03-15
• Study First Submitted QC: 2018-03-26
• Last Update Submitted: 2018-03-26
• Study First Posted: 2018-03-27
• Last Update Posted: 2018-03-27
• Primary Completion: 2021-03-15
• Study Completion: 2024-03-15

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. First established the diagnosis of HGBL DH or HGBL-NOS.
2. No previous treatment with chemotherapy and/or radiation therapy of DLBCL
3. Informed consent of the patient.

Exclusion Criteria

1. Pretreated lymphoma.

2. HIV-associated lymphoma

3. Congestive heart failure, unstable angina, severe cardiac arrhythmias and conduction disturbances, myocardial infarction.

4. 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).

5. 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%.

6. 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).

7. 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.

8. Severe mental disorders (delusions, severe depressive syndrome and other manifestations of productive symptoms) not related to specific infiltration of a central nervous system.

9. Decompensated diabetes.

10. Pregnancy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
R-DA-EPOCH-21	R-DA-EPOCH-21	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.
R-BL-M-04	R-BL-M-04	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.
R-DA-EPOCH-21 + auto-SCT	R-DA-EPOCH-21 + auto-SCT	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.
R-BL-M-04 + auto-SCT	R-BL-M-04 + auto-SCT	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.

Primary Outcome Measures

Name	Time	Method
Overall survival	2 years	Overall survival
Relapse-free survival	2 years	Relapse-free survival
Progression	2 years	Frequency of progression

Secondary Outcome Measures

Name	Time	Method
Complete remission	1 year	Frequency of complete remission
Partial remission	1 year	Frequency of partial remission

Trial Locations

Locations (1)

National Research Center for Hematology; 🇷🇺 Moscow, Russian Federation