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

Diffuse Large B Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03200015
• Other study ID #: HE16-00019
• Status: Completed
• Phase: Phase 2
• Start date: October 1, 2017
• Est. completion date: January 27, 2019

Study information

• Verified date: November 2022
• Source: Hospital Universitario Dr. Jose E. Gonzalez
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: January 27, 2019
• Est. primary completion date: August 27, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Metformin
Potentially increasing the efficacy and safety of standard chemotherapy through several mechanisms

Locations

Country	Name	City	State
Mexico	Hospital Universitario Dr. José Eleuterio González	Monterrey	Nuevo Leon

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Universitario Dr. Jose E. Gonzalez

Country where clinical trial is conducted

Mexico, 

References & Publications (3)

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. — View Citation

Asensio-López MC, Lax A, Pascual-Figal DA, Valdés M, Sánchez-Más 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. — View 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:e275. doi: 10.1038/cddis.2012.13. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	6 months
Primary	Response rates	Overall, partial and complete responses to chemoimmunotherapy	6 months
Secondary	Progression-free survival	Survival with freedom from progression	2-5 years
Secondary	Overall survival	Survival from diagnosis until death or last follow-up	2-5 years
Secondary	Event-free survival	Survival from diagnosis until death or progression	2-5 years
Secondary	Time to progression or relapse	Time from diagnosis until disease progression or relapse	2-5 years

External Links

•   Similar study registered in Clinical trials.gov