R-DA-EDOCH Versus R-CEOP90, With/Without Upfront Auto-HSCT in Young Patients With Intermediate/High-risk DLBCL

Study Overview
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Brief Summary
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Patients initially are randomized into 4 arms: Arm I: R-DA-EPOCH; Arm II: R-DA-EPOCH + auto-SCT; Arm III: R-CEOP90; Arm IV: R-CEOP90 + auto-SCT. Patients who achieved complete remission (CR) or partial remission (PR) after 6 cycles of R-DA-EPOCH or R-CEOP 90, continue to have 2 more cycles for consolidation in each arm (Arm I and Arm III), or undergo stem cell harvest and auto-HSCT following standard institutional protocols. (Arm II and Arm IV). The overall purpose of the study is to determine if R-CEOP90 followed by auto-HSCT has similar efficacy compared to that with R-DA-EPOCH.

Official Title
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A Multicenter,Randomized, Controlled (Comparative), Open, Prospective Study Evaluating an Efficacy of R-DA-EPOCH and R-CEOP90, With or Without Upfront Auto-HSCT，in Newly Diagnosed Young Patients With Intermediate/High-risk DLBCL

Conditions
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Diffuse Large B-cell Lymphoma

Intervention / Treatment
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* Drug: R-DA-EPOCH
* Drug: R-DA-EPOCH + auto-HSCT
* Drug: R-CEOP90
* Drug: R-CEOP90 + auto-HSCT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 16-60 years Newly diagnosed DLBCL No previous treatment with chemotherapy and/or radiation therapy of DLBCL Presence of 2 or more signs of unfavorable prognosis: aaIPI≥2 or aaIPI=1 with Bulk (≥7.5cm) Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Life expectancy of ≥ 6 months Adequate hematological function Offer informed consent Exclusion Criteria: Transformation of mature cell lymphomas in DLBCL Pretreated DLBCL HIV-associated DLBCL Concomitant other cancer 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

Ages Eligible for Study
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Minimum Age: 16 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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I:R-DA-EPOCH<br>Protocol involves 6 cycles. | Drug: R-DA-EPOCH<br>* R-DA-EPOCH-21 treatment without auto-SCT for DLBCL patients age between 16 to 60 years with intermediate and high risk for IPI.<br>|
| Experimental: Arm II:R-DA-EPOCH + auto-HSCT<br>Protocol involves 6 cycles. Patients with complete remission or partial remission undergo auto-HSCT after 6 cycles. | Drug: R-DA-EPOCH + auto-HSCT<br>* R-DA-EPOCH-21 treatment with auto-SCT for DLBCL patients age between 16 to 60 years with intermediate and high risk for IPI.<br>|
| Active Comparator: Arm III:R-CEOP90<br>Protocol involves 6 cycles. | Drug: R-CEOP90<br>* R-CEOP90 treatment without auto-SCT for DLBCL patients age between 16 to 60 years with intermediate and high risk for IPI.<br>|
| Active Comparator: Arm IV:R-CEOP90 + auto-HSCT<br>Protocol involves 6 cycles. Patients with complete remission or partial remission undergo auto-HSCT after 6 cycles. | Drug: R-CEOP90 + auto-HSCT<br>* R-CEOP90 treatment with auto-SCT for DLBCL patients age between 16 to 60 years with intermediate and high risk for IPI.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease-free survival | Time to disease progression is calculated in months from day of enrollment in the study until disease progression, as appropriate | Two-year survival | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| overall survival | Survival time is calculated in months from day of enrollment in the study until death, as appropriate | Two-year survival | 
| Incidence of Treatment-Emergent Adverse Events | Adverse Events (AEs) occurring during the protocol-specified reporting period are documented. | Up tp study day 240 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DLBCL, R-DA-EPOCH, R-CEOP90, auto-HSCT