A Pilot Study of Metformin Therapy in Patients With Relapsed Chronic Lymphocytic Leukemia (CLL) and Untreated CLL
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ClinicalTrials.gov Identifier: NCT01750567 |
Recruitment Status :
Recruiting
First Posted : December 17, 2012
Last Update Posted : May 12, 2022
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Condition or disease | Intervention/treatment | Phase |
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Relapsed Chronic Lymphocytic Leukemia | Drug: Metformin | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 40 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (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 |
Actual Study Start Date : | November 2012 |
Estimated Primary Completion Date : | March 2023 |
Estimated Study Completion Date : | March 2023 |

Arm | Intervention/treatment |
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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.
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Drug: Metformin
Metformin is an antidiabetic drug which is an inexpensive and generally well tolerated medication.
Other Name: Glucophage |
- Time to treatment failure [ Time Frame: Until the patient meets failure criteria and stops Metformin; up to 6 months after start of metformin therapy and yearly thereafter. ]
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 (0-3) 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) associated with a bone marrow biopsy result indicating advanced stage CLL (packed CLL marrow).
- 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. ]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: Until the patient meets failure criteria and stops Metformin ]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.
- Change in size of clinically appreciated lymphadenopathy in cm and splenomegaly while on metformin therapy [ Time Frame: Baseline up to 3 months after completing metformin therapy ]The proportion of patients that begin metformin therapy with these conditions will be summarized, along with the proportions at study defined clinical assessment points during therapy. No statistical models will be employed, but proportions and 95% exact binomial confidence intervals will be reported for descriptive purposes.
- Change in number of clinically appreciated lymphadenopathy and splenomegaly while on metformin therapy [ Time Frame: Baseline up to 3 months after completing metformin therapy ]The proportion of patients that begin metformin therapy with these conditions will be summarized, along with the proportions at study defined clinical assessment points during therapy. No statistical models will be employed, but proportions and 95% exact binomial confidence intervals will be reported for descriptive purposes.

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Ages Eligible for Study: | 18 Years to 80 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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.
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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
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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.
Exclusion Criteria:
- Patients with active CLL disease requiring urgent chemotherapy
- Patients may not be receiving any other investigational agents.
- Patients less than 30 days from last treatment for CLL.
- History of allergic reactions attributed to metformin or other biguanides.
- Known diabetes (type 1 or 2), fasting glucose > or equal to 7.0 mmol/L (126 mg/dL), or HgbA1C > 6.5
- 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).
- 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
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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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01750567
United States, Michigan | |
University of Michigan Comprehensive Cancer Center | Recruiting |
Ann Arbor, Michigan, United States, 48109 | |
Contact: Sami Malek, MD 734-936-5310 smalek@med.umich.edu | |
Contact: Erlene Seymour, MD 734-647-2892 ekuizon@med.umich.edu | |
Principal Investigator: Sami Malek, MD | |
Sub-Investigator: Daniel Lebovic, MD | |
Sub-Investigator: Erlene Seymour, MD |
Principal Investigator: | Sami Malek, MD | University of Michigan Rogel Cancer Center |
Responsible Party: | University of Michigan Rogel Cancer Center |
ClinicalTrials.gov Identifier: | NCT01750567 |
Other Study ID Numbers: |
UMCC 2012.025 |
First Posted: | December 17, 2012 Key Record Dates |
Last Update Posted: | May 12, 2022 |
Last Verified: | May 2022 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Relapsed Chronic Lymphocytic Leukemia untreated CLL patients genomic deletion 11q |
Leukemia Leukemia, Lymphoid Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, B-Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders |
Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Metformin Hypoglycemic Agents Physiological Effects of Drugs |