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

Diffuse Large B-Cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02842931
• Other study ID #: DLBCL-2015
• Status: Recruiting
• Phase: Phase 3
• First received: March 11, 2016
• Last updated: July 20, 2016
• Start date: February 2015
• Est. completion date: February 2023

Study information

• Verified date: July 2016
• Source: National Research Center for Hematology, Russia
• Contact: Aminat Magomedova, MD, PhD
• Phone: 495-613-2446
• Email: maminat[@]mail.ru
• Is FDA regulated: No
• Health authority: Russia: Ministry of Health of the Russian Federation
• Study type: Interventional

Clinical Trial 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.

Description:

Patients initially are randomized into 4 arms:

1. st arm R-DA-EPOCH-21

2. nd arm R-mNHL-BFM-90

3. rd arm R-DA-EPOCH-21 + auto-SCT

4. 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: February 2023
• Est. primary completion date: February 2020
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diffuse Large B-Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• R-DA-EPOCH-21
R-DA-EPOCH-21 treatment without auto-SCT for DLBCL patients younger than 60 years with intermediate and high risk for IPI
• R-DA-EPOCH-21 + auto-SCT
R-DA-EPOCH-21 treatment with auto-SCT for DLBCL patients younger than 60 years with intermediate and high risk for IPI
• R-mNHL-BFM-90
R-mNHL-BFM-90 without auto-SCT in patients with DLBCL under the age of 60 years with intermediate and high risk for IPI
• R-mNHL-BFM-90 + auto-SCT
R-mNHL-BFM-90 with auto-SCT in patients with DLBCL under the age of 60 years with intermediate and high risk for IPI

Locations

Country	Name	City	State
Russian Federation	National Research Center for Hematology	Moscow

Sponsors (2)

Lead Sponsor	Collaborator
National Research Center for Hematology, Russia	National Research Center for Hematology

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	168 day	No
Secondary	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	Five-year survival	No
Secondary	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	Five-year survival	No
Secondary	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	Five-year survival	No