Diffuse Large B-Cell Lymphoma
Conditions
Keywords
diffuse large b-cell lymphoma (DLBCL),, lymphoma
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.
Interventions
DRUGMetformin
Metformin upregulates AMPK activity which has been shown to have an anti-proliferative effect on lymphoma cells.
DRUGRituximab
monoclonal antibody against protein CD20 primarily found on the surface of B-cells
DRUGCyclophosphamide
Interferes with DNA replication
DRUGDoxorubicin
anthracycline antitumor antibiotic
DRUGVincristine
Inhibits cell mitosis causing cell death.
DRUGPrednisone
a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases
DRUGpegfilgrastim
stimulates the level of white blood cells (neutrophils).
Sponsors
Rush University Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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 2. No prior therapy for diagnosis of DLBCL 3. 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 4. Eastern Cooperative Oncology Group performance score of 0-2 5. Life expectancy of at least 6 months 6. No history of medication dependent diabetes mellitus 7. Required screening laboratory data (within 4 weeks prior to start of study drug) -
Exclusion criteria
1. 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 2. Known histological transformation from indolent non-Hodgkins Lymphoma (NHL) or chronic lymphocytic leukemia (CLL) to an aggressive form of NHL (ie, Richter transformation) 3. Double or triple hit lymphomas 4. Known active cent4ral nervous system or leptomeningeal lymphoma 5. Presence of known intermediate or high-grade myelodysplastic syndrome 6. History of a non-lymphoid malignancy within the last 3 years (see protocol for exceptions) 7. Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of start of study 8. 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. 9. HIV positive 10. Ongoing inflammatory bowel disease 11. Ongoing alcohol or drug addiction 12. Pregnancy 13. History of prior allogeneic bone marrow progenitor cell or solid organ transplantation. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 2 year | rate of progression in patients 2 years after diagnosis |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| R-CHOP With Metformin 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. | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | R-CHOP With Metformin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 1 / 5 |
Outcome results
Primary
Progression Free Survival
rate of progression in patients 2 years after diagnosis
Time frame: 2 year
Population: The primary endpoint (2 year PFS rate) could not be determined as study was terminated prematurely prior to subjects reaching this milestone with confidentiality of concern for reporting collected data.