Lenalidomide in Combination With R-DA-EPOCH in Patients With Untreated DLBCL With MYC Rearrangement

Study Overview
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Brief Summary
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The prognosis of DLBCL with MYC rearrangement is dismal. Previous study showed that lenalidomide in combination with R-CHOP showed promising therapeutic activity and that R-DA EPOCH was superior compared to R-CHOP regimen in this cohort of patients. The investigators therefore design this phase I/II study to investigate the safety and efficacy of lenalidomide in combination with R-DA EPOCH in patients with untreated MYC-rearranged DLBCL.

Official Title
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A Phase II, Prospective, Single-center Study of Lenalidomide in Combination With R-DA-EPOCH in Patients With Untreated DLBCL With MYC Rearrangement

Conditions
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DLBCL, Untreated, MYC Gene Rearrangement

Intervention / Treatment
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* Drug: Lenalidomide
* Drug: Rituximab
* Drug: Etoposide
* Drug: Doxorubicin
* Drug: Vincristine
* Drug: Cyclophosphamide
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed DLBCL with MYC rearrangement according to WHO 2016 criteria, excluding PMBCL, PCNSL, HIV-associated lymphoma. ECOG PS 0-2 Age 18-60 years old Expected survival ≥ 12 weeks A measurable or evaluable disease at the time of enrolment (diameter ≥1.5cm) Understand and voluntarily sign an informed consent form, able to adhere to the study visit schedule and other protocol requirements. Exclusion Criteria: Women who are pregnant or lactating. Patients have breeding intent in 12 months or cannot take effective contraceptive measures during the trial measures Active hepatitis B or hepatitis C virus infection, as well as acquired, congenital immune deficiency diseases, including but not limited to HIV infected persons Previous exposure to any anti-tumor therapy Poor hepatic and/or renal function, defined as total bilirubin, ALT, AST, Cr more than two fold of upper normal level,Ccr# 50 mL/min unless these abnormalities were related to the lymphoma History of DVT or PE within past 12 months Poor bone-marrow reserve, defined as neutrophil count less than 1.5×109/L or platelet count less than 75×109/L, unless caused by bone marrow infiltration New York Heart Association class III or IV cardiac failure; or Ejection fraction less than 50%;or history of following disease in past 6 months: acute coronary syndrome#acute heart failure#severe ventricular arrhythmia CNS or meningeal involvement Known sensitivity or allergy to investigational product Major surgery within three weeks Patients receiving organ transplantation Patients with secondary tumour, excluding cured (5 years without relapse) in situ Non-melanoma skin cancer. superficial bladder cancer, in situ cervical cancer, Gastrointestinal intramucous carcinoma and breast cancer Presence of Grade III nervous toxicity within past two weeks Active and severe infectious diseases Any potential drug abuse, medical, psychological or social conditions whichmay disturb this investigation and assessment In any conditions which investigator considered ineligible for this study Patients with histological transformation.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: R2-DA-EPOCH<br> | Drug: Lenalidomide<br>* Lenalidomide 10mg/d#15mg/d#20mg/d#25mg/d d1 d10# 21days a cycle<br>Drug: Rituximab<br>* Rituximab 375 mg/m2，IV, d0<br>Drug: Etoposide<br>* Etoposide 50 mg/m2/day CI24h d1-d4<br>Drug: Doxorubicin<br>* Doxorubicin 10 mg/m2/day CI24h d1-d4<br>Drug: Vincristine<br>* Vincristine 0.4mg/m2/day CI24h d1-d4<br>Drug: Cyclophosphamide<br>* Cyclophosphamide 750 mg/m2/day IV d5<br>Drug: Prednisone<br>* Prednisone 60 mg/m2/bid oral or IV d1-d5<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum tolerated dose and dose limited toxicity |  | 21 days after first cycle of R2-DA-EPOCH regimen (each cycle is 21 days) | 
| Overall response rate |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progressive free survival | from date of inclusion to date of progression, relapse, or death from any cause | 2 years | 
| Overall survival | from the date of inclusion to date of death, irrespective of cause | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DLBCL, MYC Gene rearrangement, Lenalidomide, R-DA EPOCH