A Pilot Study of Metformin Therapy in Patients With Relapsed Chronic Lymphocytic Leukemia (CLL) and Untreated CLL
Metformin is an antidiabetic drug which is an inexpensive and generally well tolerated medication. More recently metformin has been shown to act against carcinomas by two mechanisms: 1) an indirect, insulin‐dependent mechanism which sensitizes tissues to insulin, inhibits hepatic gluconeogenesis, and stimulates uptake of glucose in muscle, thereby reducing fasting blood glucose and circulating levels of insulin, lowering the pro survival activity of the insulin/INSR axis, and 2) a direct, insulin‐independent mechanism which activates the AMP‐activated protein kinase (AMPK) pathway and leads to inhibition of the mTOR pathway. Given the investigators preliminary published data on insulin and mTOR inhibition metformin is an attractive candidate for a pilot clinical trial in CLL patients.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Pilot Study of Metformin Therapy in Patients With Relapsed Chronic Lymphocytic Leukemia and Untreated CLL Patients With Genomic Deletion 11q|
- Time to treatment failure [ Time Frame: every 3 months ] [ Designated as safety issue: Yes ]
Time to treatment failure: While patients are on metformin therapy, time to treatment failure will be defined as one or all of the following criteria:
- ALC > 5000 on 3 occasions after start of metformin treatment and increasing by 25% or more on each occasion, which will be measured every 3 months.
- An increase of Rai Stage by one stage.
- An increase in any lymph node by >50% as assessed by either physical exam (all patients) or CT scanning (only if ordered as part of routine clinical management).
- Worsening cytopenias (Hemoglobin <11 g/dl or platelet count <100,000)
- Time to first therapy (TTFT) in previously untreated 11q CLL subsets only. [ Time Frame: from time of diagnosis to time of first treatment with anti‐neoplastic chemotherapy. ] [ Designated as safety issue: Yes ]to evaluate TTFT in untreated patients, the product‐limit method of Kaplan and Meier will be used similarly to the primary endpoint. The main difference between this endpoint and the primary endpoint is that TTFT will be defined from the date of CLL diagnosis for untreated delq11 patients
- changes in the rate of increase of absolute lymphocyte count while on metformin therapy [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]longitudinal lymphocyte counts will be modeled using mixed models methodology, whereby both fixed effects (dose of metformin) and random effects (intercept - starting lymphocyte count) can be modeled.
|Study Start Date:||October 2012|
|Estimated Study Completion Date:||October 2016|
|Estimated Primary Completion Date:||October 2016 (Final data collection date for primary outcome measure)|
Experimental: Metformin (Glucophage)
The starting dose of metformin will be 500 mg po daily for one week. The dose can be escalated to 500 mg twice a day after one week, and further escalated to the final dose of 1000 mg twice a day in week 3 if the medication is tolerated without adverse side effects (refer to holding parameters described in section 9.3.3). All doses should be administered with food to decrease gastrointestinal upset.
Metformin is an antidiabetic drug which is an inexpensive and generally well tolerated medication.
Other Name: Glucophage
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center||Recruiting|
|Ann Arbor, Michigan, United States, 48109|
|Contact: Sami Malek, MD 734-936-5310 email@example.com|
|Contact: Erlene Seymour, MD 734-647-2892 firstname.lastname@example.org|
|Principal Investigator: Sami Malek, MD|
|Sub-Investigator: Daniel Lebovic, MD|
|Sub-Investigator: Erlene Seymour, MD|
|Principal Investigator:||sami Malek, MD||University of Michigan Cancer Center|