Relapsed Chronic Lymphocytic LeukemiaPhase 2NCT01750567
A Pilot Study of Metformin Therapy in Patients With Relapsed Chronic Lymphocytic Leukemia (CLL) and Untreated CLL
A Phase 2 study testing Metformin in people with Relapsed Chronic Lymphocytic Leukemia, run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Relapsed Chronic Lymphocytic Leukemia
- What is being tested?
- Metformin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2012to 28 Feb 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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
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- 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
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
About this study
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
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[1] metformin is an attractive candidate for a pilot clinical trial in CLL patients.
- Conditions
- Relapsed Chronic Lymphocytic Leukemia
- Being tested
- Metformin
- Keywords
- Relapsed Chronic Lymphocytic Leukemia, untreated CLL patients, genomic deletion 11q
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Glucophage
Metformin is an antidiabetic drug which is an inexpensive and generally well tolerated medication.
| Study group | Role | What they receive |
|---|---|---|
| Metformin (Glucophage) | Experimental | 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. Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 (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).
Measured: Until the patient meets failure criteria and stops Metformin; up to 6 months after start of metformin therapy and yearly thereafter, assessed up to 12 years
Secondary outcomes (4)
Time to First Therapy (TTFT) in Previously Untreated 11q CLL Subsets Only.
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
Measured: from time of diagnosis to time of first treatment with anti-neoplastic chemotherapy, assessed up to 12 years
Changes in the Rate of Increase of Absolute Lymphocyte Count While on Metformin Therapy
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.
Measured: Until the patient meets failure criteria and stops Metformin, assessed up to 12 years
Change in Size of Clinically Appreciated Lymphadenopathy in cm and Splenomegaly While on 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.
Measured: Baseline up to 3 months after completing metformin therapy, assessed up to 12 years
Change in Number of Clinically Appreciated Lymphadenopathy and Splenomegaly While on Metformin Therapy
The number 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.
Measured: Baseline up to 3 months after completing metformin therapy, assessed up to 12 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2012 (estimated)
- Study startNov 2012
- Primary completion28 Feb 2025
- Study completion28 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Relapsed Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sami Malek, MD, Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01750567
- Sponsor's protocol ID
- UMCC 2012.025
- Status last verified
- Jul 2026
- First submitted
- 2 Oct 2012
- Last updated
- 20 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01750567
- Acronym / sponsor ID
- UMCC 2012.025
- Conditions
- Relapsed Chronic Lymphocytic Leukemia
- Keywords
- Relapsed Chronic Lymphocytic Leukemia, untreated CLL patients, genomic deletion 11q
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- Nov 2012 (actual)
- Primary completion
- 28 Feb 2025 (actual)
- Study completion
- 28 Feb 2025 (actual)
- First posted
- 17 Dec 2012 (estimated)
- Results
- Posted 20 Jul 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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[1] metformin is an attractive candidate for a pilot clinical trial in CLL patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Metformin (Glucophage) | Experimental | Drug: MetforminThe 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Patients should have a confirmed diagnosis of chronic lymphocytic leukemia defined as all of the following:
- 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:
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminAlso: GlucophageMetformin is an antidiabetic drug which is an inexpensive and generally well tolerated medication. | Drug | Metformin (Glucophage) |
Primary outcome
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, assessed up to 12 years
While patients are on metformin therapy, time to treatment failure will be defined as one or all of the following criteria: 1. 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. 2. An increase of Rai Stage (0-3) by one stage. 3. 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). 4. Worsening cytopenias (Hemoglobin <11 g/dl) associated with a bone marrow biopsy result indicating advanced stage CLL (packed CLL marrow).
4 secondary outcomes
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, assessed up to 12 years
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, assessed up to 12 years
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, assessed up to 12 years
Change in Number of Clinically Appreciated Lymphadenopathy and Splenomegaly While on Metformin Therapy
Time frame: Baseline up to 3 months after completing metformin therapy, assessed up to 12 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sami Malek, MD principal investigator
University of Michigan Rogel Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin in people with Relapsed Chronic Lymphocytic Leukemia, run by University of Michigan Rogel Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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, assessed up to 12 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2026.