Rituximab, Cyclophosphamide, Vincristine and Prednisone (R-CHOP) Plus Metformin in Diffuse Large-B-cell Lymphoma

Study Overview
=================
Brief Summary
-----------------
Evaluation of the safety and effectiveness of metformin as an adjunct to RCHOP chemotherapy for patients with newly diagnosed diffuse large-B cell lymphoma

Detailed Description
-----------------
Patients with newly diagnosed diffuse large-B cell non Hodgkin lymphoma, irrespective of cell of origin status will receive metformin in combination to Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP) chemotherapy for 6 cycles, until response evaluation as reported elsewhere: 1.- Rituximab 375 mg/m2 IV, day 1. 2.- Cyclophosphamide 750 mg/m2 IV, day 1. 3.- Doxorubicin 50 mg/m2 IV day 1. 4.- Vincristine 1.4 mg/m2 IV (2 mg maximum dose). 5.- Prednisone 60 mg/m2 PO days 1-5. Six cycles every 21 days. Metformin will be added and administered in an outpatient basis, starting with 425 mg twice a day for 1 week, followed by 850 mg twice a day for 1 week, and lastly 850 mg every 8 hours maximum dose until re-staging. Laboratory tests will be performed serially.

Official Title
-----------------
Effect of Metformin in Combination With R-CHOP for the First Line Treatment of Patients With Diffuse Large B-cell Lymphoma

Conditions
-----------------
Diffuse Large B Cell Lymphoma

Intervention / Treatment
-----------------
* Drug: Metformin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with newly diagnosed nodal diffuse large-B cell non Hodgkin lymphoma according to the 2008 World Health Organization classification for lymphoid malignancies No previous treatment other than prednisone or equivalent glucocorticoid up to 60 mg/m2 for 14 days Good performance status (Eastern Cooperative Oncology Group scale 0-2) Life expectancy >6 months Independently of the diagnosis of diabetes mellitus (any type) Exclusion Criteria: History of intolerance or hypersensitivity reactions to metformin Primary central nervous system lymphoma History of other previous malignant neoplastic diseases <5 years prior to enrollment Evidence of systemic infection at the time of study HIV, hepatitis C or B virus infection Aspartate transaminase or alanine transaminase >2x upper limit of normal, bilirubin >2.5 times upper limit of normal Serum creatinine >1.5 mg/dL or chronic renal disease Cardiac insufficiency (New York Heart Association scale >1 or ejection fraction <50%) History of transformation from an indolent lymphoma Pregnancy History of lactic acidosis or alcoholism

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin arm<br>Metformin 850 mg tablets. Initial dose 425 mg twice a day for 1 week, followed by 850 mg twice a day for 1 week, titrated to a maximum dose 850 mg every 8 hours until disease response evaluation study date (Computed tomography or positron emission tomography) | Drug: Metformin<br>* Potentially increasing the efficacy and safety of standard chemotherapy through several mechanisms<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | 6 months | 
| Response rates | Overall, partial and complete responses to chemoimmunotherapy | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Survival with freedom from progression | 2-5 years | 
| Overall survival | Survival from diagnosis until death or last follow-up | 2-5 years | 
| Event-free survival | Survival from diagnosis until death or progression | 2-5 years | 
| Time to progression or relapse | Time from diagnosis until disease progression or relapse | 2-5 years |