Metformin in Combination With Standard Induction Therapy for Large B-cell Lymphoma (DLBCL)
Condition: Diffuse Large B-Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
Intervention: Metformin; Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; pegfilgrastim
Intervention description: Metformin upregulates AMPK activity which has been shown to have an anti-proliferative effect on lymphoma cells.; monoclonal antibody against protein CD20 primarily found on the surface of B-cells; Interferes with DNA replication; anthracycline antitumor antibiotic; Inhibits cell mitosis causing cell death.; a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases; stimulates the level of white blood cells (neutrophils).
Intervention MeSH terms: Metformin; Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Vincristine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: diffuse large b-cell lymphoma (DLBCL),; lymphoma

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)
    

Eligibility criteria:

        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.

             -