A Pilot Study of Metformin Therapy in Patients With Relapsed Chronic Lymphocytic Leukemia (CLL) and Untreated CLL

Prior treatment

• Patients may not be receiving any other investigational agents.
• Currently taking metformin, sulfonylureas, thiazolidinediones or insulin for any reason
• Current or planned pregnancy or lactation in women of child bearing age (confirmed by negative pregnancy test prior to start of therapy).

Other illness

• Patients with active CLL disease requiring urgent chemotherapy
• History of allergic reactions attributed to metformin or other biguanides.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection and sepsis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Conditions which would increase risk of lactic acidosis including:
  • Known alcoholism or ingestion of more than 3 alcoholic beverages per day
  • History of congestive heart failure defined as NYHA class III or IV
  • History of metabolic acidosis
  • Ongoing or active infection concerning for sepsis or SIRS

Lab values

• Known diabetes (type 1 or 2), fasting glucose \> or equal to 7.0 mmol/L (126 mg/dL), or HgbA1C \> 6.5

Other

• Patients less than 30 days from last treatment for CLL.

• Patients should have a confirmed diagnosis of chronic lymphocytic leukemia defined as all of the following:
  • ALC \> 5000
  • Positive for either CD19 or CD 20 together with CD23 and CD5.
  • Less than 55% atypical cells
• Patients who relapse after receiving a one or more courses of fludarabine, bendamustine, cytoxan, rituxan, chlorambucil, or campath based therapy.
• Patients should have findings of relapse by one or both of the following:
  • ALC \> 5000 on 2 consecutive occasions and increasing
  • Any increase in lymphadenopathy over best response that has persisted for more than 3 months
• Patient with confirmed del11q mutation may be included if untreated.
• Age \> or equal to 18 years old and \< 80 years of age during the course of therapy
• ECOG performance 0-2
• Life expectancy \> 12 months
• Patients must have normal organ function as defined as below:
  • AST and ALT \< 2 times the upper limit of normal
  • alkaline phosphatase \< 2 ULN
  • serum conjugated bilirubin \< 1.5 ULN (exception of Gilbert disease)
  • serum creatinine less than or equal to 1.5 in males, or 1.4 in females
  • GFR \> 59
• Ability to understand and the willingness to sign a written informed consent document
• Patient must be able to drink and eat more than 75% of their usual daily meals.