Clinical trial NCT03200015: Rituximab, Cyclophosphamide, Vincristine and Prednisone (R-CHOP) Plus Metformin in Diffuse Large-B-cell Lymphoma
Official title: Effect of Metformin in Combination With R-CHOP for the First Line Treatment of Patients With Diffuse Large B-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diffuse Large B Cell Lymphoma
Lead sponsor: Hospital Universitario Dr. Jose E. Gonzalez
Sponsor class: OTHER
First posted: 2017-06-27
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence of treatment-emergent adverse events
timeFrame: 6 months
measure: Response rates
timeFrame: 6 months
Secondary outcomes:
measure: Progression-free survival
timeFrame: 2-5 years
measure: Overall survival
timeFrame: 2-5 years
measure: Event-free survival
timeFrame: 2-5 years
measure: Time to progression or relapse
timeFrame: 2-5 years
Other outcomes:
Locations:
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. José Eleuterio González
state: Nuevo Leon
Study officials:
affiliation: Hospital Universitario Dr. José Eleuterio González
name: David Gómez-Almaguer, MD
role: STUDY_CHAIR
References:
citation: Asensio-Lopez MC, Lax A, Pascual-Figal DA, Valdes M, Sanchez-Mas J. Metformin protects against doxorubicin-induced cardiotoxicity: involvement of the adiponectin cardiac system. Free Radic Biol Med. 2011 Nov 15;51(10):1861-71. doi: 10.1016/j.freeradbiomed.2011.08.015. Epub 2011 Aug 25.
citation: Shi WY, Xiao D, Wang L, Dong LH, Yan ZX, Shen ZX, Chen SJ, Chen Y, Zhao WL. Therapeutic metformin/AMPK activation blocked lymphoma cell growth via inhibition of mTOR pathway and induction of autophagy. Cell Death Dis. 2012 Mar 1;3(3):e275. doi: 10.1038/cddis.2012.13.
citation: Alkhatib Y, Abdel Rahman Z, Kuriakose P. Clinical impact of metformin in diabetic diffuse large B-cell lymphoma patients: a case-control study. Leuk Lymphoma. 2017 May;58(5):1130-1134. doi: 10.1080/10428194.2016.1239822. Epub 2016 Oct 5.