Back to resultsMetformin in Combination With Standard Induction Therapy for Large B-cell Lymphoma (DLBCL) (DLBCL)
Primary Purpose
Diffuse Large B-Cell Lymphoma
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Metformin
Rituximab
Cyclophosphamide
Doxorubicin
Vincristine
Prednisone
pegfilgrastim
Sponsored by
About this trial
This is an interventional treatment trial for Diffuse Large B-Cell Lymphoma focused on measuring diffuse large b-cell lymphoma (DLBCL),, lymphoma
Eligibility Criteria
Inclusion Criteria:
Diagnosis of Diffuse Large B-cell Lymphoma (DLBCL) as documented by medical records and with histology based on criteria established by the World Health Organization
a. subtyping is required for DLBCL
- No prior therapy for diagnosis of DLBCL
- Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of equal to or greater than 1 lesion that measures >1.5 cm in the longest diameter and > 1.0 cm in the longest perpendicular diameter assessed by CT or MRI) or bone marrow involvement
- Eastern Cooperative Oncology Group performance score of 0-2
- Life expectancy of at least 6 months
- No history of medication dependent diabetes mellitus
- Required screening laboratory data (within 4 weeks prior to start of study drug) -
Exclusion Criteria:
- Patients already on any class of anti-diabetic medication including metformin, insulin analogues, sulfonylureas, thiazolidinediones (TZDs) and the incretin-based therapies or clear need for therapeutic intervention based on fasting blood glucose
- Known histological transformation from indolent non-Hodgkins Lymphoma (NHL) or chronic lymphocytic leukemia (CLL) to an aggressive form of NHL (ie, Richter transformation)
- Double or triple hit lymphomas
- Known active cent4ral nervous system or leptomeningeal lymphoma
- Presence of known intermediate or high-grade myelodysplastic syndrome
- History of a non-lymphoid malignancy within the last 3 years (see protocol for exceptions)
- Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of start of study
- Ongoing, drug-induced liver injury, chronic active Hepatitis C Virus (HCV), chronic active Hepatitis B Virus (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
- HIV positive
- Ongoing inflammatory bowel disease
- Ongoing alcohol or drug addiction
- Pregnancy
History of prior allogeneic bone marrow progenitor cell or solid organ transplantation.
-
Sites / Locations
- Rush University Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
R-CHOP with Metformin
Arm Description
Rituximab 375 mg/m2 IV infusion Day 1 Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Vincristine 1.4 mg/m2 (2 mg cap) IV Day 1 Prednisone 100 mg PO Days 1-5 Pegfilgrastim 6 mg subcutaneous within 72 hours of cyclophosphomide Metformin 500 mg PO daily D 1-7, 500 mg twice daily D8-21, 850 mg twice daily D22 - 30days post study. Cycles are 21 days. Above treatment given for 4 cycles, then restaging done. If complete response (CR) or partial response (PR), 2 more cycle given; stable disease (SD) or progressive disease (PD)- salvage therapy off study.
Outcomes
Primary Outcome Measures
Progression Free Survival
rate of progression in patients 2 years after diagnosis
Secondary Outcome Measures
Full Information
NCT ID
NCT02531308
First Posted
July 27, 2015
Last Updated
September 21, 2022
Sponsor
Rush University Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT02531308
Brief Title
Metformin in Combination With Standard Induction Therapy for Large B-cell Lymphoma (DLBCL)
Acronym
DLBCL
Official Title
A Phase ll Study Evaluating the Efficacy and Safety of Metformin in Combination With Standard Induction Therapy (RM-CHOP) for Previously Untreated Aggressive Diffuse Large B-cell Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Terminated
Why Stopped
poor accrual
Study Start Date
July 2015 (undefined)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
July 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rush University Medical Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Evaluation of impact of metformin on 2 year progression-free survival (PFS) rate in subjects with previously untreated DLBCL when added to standard induction therapy. (R-CHOP)
Detailed Description
Newly diagnosed histologically confirmed CD20 positive previously untreated diffuse large B-cell lymphoma to receive up to 4-6 cycles (21 day cycles) of:
R-CHOP: Rituximab 375 mg/m2 IV infusion Day 1 Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Vincristine 1.4 mg/m2 IV Day 1 (cap @ 2mg) Prednisone 100mg PO daily Days 1-5 Pegfilgrastim 6 mg subcutaneously within 72 if start if cycle Metformin 500 mg PO daily Cycle 1 Days 1-7 Metformin 500 mg PO twice daily Cycle 1 Days 7-21 Metformin 850 mg PO twice daily starting on day 22 and and continuing throughout remainder of cycles plus 22 days post treatment.
Restaging will be done after the 4th cycle is complete. Subjects will be monitored with labs and physical exams throughout the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-Cell Lymphoma
Keywords
diffuse large b-cell lymphoma (DLBCL),, 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
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
R-CHOP with Metformin
Arm Type
Experimental
Arm Description
Rituximab 375 mg/m2 IV infusion Day 1 Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Vincristine 1.4 mg/m2 (2 mg cap) IV Day 1 Prednisone 100 mg PO Days 1-5 Pegfilgrastim 6 mg subcutaneous within 72 hours of cyclophosphomide Metformin 500 mg PO daily D 1-7, 500 mg twice daily D8-21, 850 mg twice daily D22 - 30days post study.
Cycles are 21 days. Above treatment given for 4 cycles, then restaging done. If complete response (CR) or partial response (PR), 2 more cycle given; stable disease (SD) or progressive disease (PD)- salvage therapy off study.
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet.
Intervention Description
Metformin upregulates AMPK activity which has been shown to have an anti-proliferative effect on lymphoma cells.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan, Zytux, Mab thera
Intervention Description
monoclonal antibody against protein CD20 primarily found on the surface of B-cells
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Endoxan, Cytoxan, Neosar, Procytox, Revimmune, Cycloblastin
Intervention Description
Interferes with DNA replication
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
Adriamycin
Intervention Description
anthracycline antitumor antibiotic
Intervention Type
Drug
Intervention Name(s)
Vincristine
Other Intervention Name(s)
Oncovin
Intervention Description
Inhibits cell mitosis causing cell death.
Intervention Type
Drug
Intervention Name(s)
Prednisone
Other Intervention Name(s)
Deltasone
Intervention Description
a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases
Intervention Type
Drug
Intervention Name(s)
pegfilgrastim
Other Intervention Name(s)
Neulasta
Intervention Description
stimulates the level of white blood cells (neutrophils).
Primary Outcome Measure Information:
Title
Progression Free Survival
Description
rate of progression in patients 2 years after diagnosis
Time Frame
2 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of Diffuse Large B-cell Lymphoma (DLBCL) as documented by medical records and with histology based on criteria established by the World Health Organization
a. subtyping is required for DLBCL
No prior therapy for diagnosis of DLBCL
Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of equal to or greater than 1 lesion that measures >1.5 cm in the longest diameter and > 1.0 cm in the longest perpendicular diameter assessed by CT or MRI) or bone marrow involvement
Eastern Cooperative Oncology Group performance score of 0-2
Life expectancy of at least 6 months
No history of medication dependent diabetes mellitus
Required screening laboratory data (within 4 weeks prior to start of study drug) -
Exclusion Criteria:
Patients already on any class of anti-diabetic medication including metformin, insulin analogues, sulfonylureas, thiazolidinediones (TZDs) and the incretin-based therapies or clear need for therapeutic intervention based on fasting blood glucose
Known histological transformation from indolent non-Hodgkins Lymphoma (NHL) or chronic lymphocytic leukemia (CLL) to an aggressive form of NHL (ie, Richter transformation)
Double or triple hit lymphomas
Known active cent4ral nervous system or leptomeningeal lymphoma
Presence of known intermediate or high-grade myelodysplastic syndrome
History of a non-lymphoid malignancy within the last 3 years (see protocol for exceptions)
Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of start of study
Ongoing, drug-induced liver injury, chronic active Hepatitis C Virus (HCV), chronic active Hepatitis B Virus (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
HIV positive
Ongoing inflammatory bowel disease
Ongoing alcohol or drug addiction
Pregnancy
History of prior allogeneic bone marrow progenitor cell or solid organ transplantation.
-
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Reem Karmali, MD
Organizational Affiliation
Assistant Professor of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Metformin in Combination With Standard Induction Therapy for Large B-cell Lymphoma (DLBCL)
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