A Phase II Pilot Study of Metformin Therapy in Patients With Relapsed Chronic Lymphocytic Leukemia and Untreated CLL Patients With Genomic Deletion 11q

Inclusion Criteria:

1. 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

2. Patients who relapse after receiving a one or more courses of fludarabine,
bendamustine, cytoxan, rituxan, chlorambucil, or campath based therapy.

3. 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

4. Patient with confirmed del11q mutation may be included if untreated.

5. Age > or equal to 18 years old and < 80 years of age during the course of therapy

6. ECOG performance 0‐2 (see Appendix A)

7. Life expectancy > 12 months

8. 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
bilirubin < ULN (exception of Gilbert disease) serum creatinine less than or equal to
1.5 in males, or 1.4 in female GFR > 60

9. Ability to understand and the willingness to sign a written informed consent document

10. Patient must be able to drink and eat more than 75% of their usual daily meals.

Exclusion Criteria:

1. Patients with active CLL disease requiring urgent chemotherapy

2. Patients may not be receiving any other investigational agents.

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

4. History of allergic reactions attributed to metformin or other biguanides.

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

6. Currently taking metformin, sulfonylureas, thiazolidinediones or insulin for any
reason

7. Current or planned pregnancy or lactation in women of child bearing age (confirmed by
negative pregnancy test prior to start of therapy).

8. 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

9. 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 17 History of metabolic acidosis
Ongoing or active infection concerning for sepsis or SIRS