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

Primary Purpose

Diffuse Large B Cell Lymphoma

Status
Completed
Phase
Phase 2
Locations
Mexico
Study Type
Interventional
Intervention
Metformin
Sponsored by
Hospital Universitario Dr. Jose E. Gonzalez
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B Cell Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hospital Universitario Dr. José Eleuterio González

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Metformin arm

Arm Description

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)

Outcomes

Primary Outcome Measures

Incidence of treatment-emergent adverse events
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Response rates
Overall, partial and complete responses to chemoimmunotherapy

Secondary Outcome Measures

Progression-free survival
Survival with freedom from progression
Overall survival
Survival from diagnosis until death or last follow-up
Event-free survival
Survival from diagnosis until death or progression
Time to progression or relapse
Time from diagnosis until disease progression or relapse

Full Information

First Posted
May 24, 2017
Last Updated
November 3, 2022
Sponsor
Hospital Universitario Dr. Jose E. Gonzalez
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1. Study Identification

Unique Protocol Identification Number
NCT03200015
Brief Title
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

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
October 1, 2017 (Actual)
Primary Completion Date
August 27, 2018 (Actual)
Study Completion Date
January 27, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hospital Universitario Dr. Jose E. Gonzalez

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B Cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Metformin arm
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
Potentially increasing the efficacy and safety of standard chemotherapy through several mechanisms
Primary Outcome Measure Information:
Title
Incidence of treatment-emergent adverse events
Description
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame
6 months
Title
Response rates
Description
Overall, partial and complete responses to chemoimmunotherapy
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Progression-free survival
Description
Survival with freedom from progression
Time Frame
2-5 years
Title
Overall survival
Description
Survival from diagnosis until death or last follow-up
Time Frame
2-5 years
Title
Event-free survival
Description
Survival from diagnosis until death or progression
Time Frame
2-5 years
Title
Time to progression or relapse
Description
Time from diagnosis until disease progression or relapse
Time Frame
2-5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Gómez-Almaguer, MD
Organizational Affiliation
Hospital Universitario Dr. José Eleuterio González
Official's Role
Study Chair
Facility Information:
Facility Name
Hospital Universitario Dr. José Eleuterio González
City
Monterrey
State/Province
Nuevo Leon
ZIP/Postal Code
64610
Country
Mexico

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
No plans for a sharing plan pre-determined
Citations:
PubMed Identifier
21907790
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.
Results Reference
background
PubMed Identifier
22378068
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.
Results Reference
background
PubMed Identifier
27701994
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.
Results Reference
background
Links:
URL
https://clinicaltrials.gov/ct2/show/record/NCT02531308
Description
Similar study registered in Clinical trials.gov

Learn more about this trial

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

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