Metformin for Chronic Lymphocytic Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Michigan Rogel Cancer Center

Must not be taking: Metformin, Sulfonylureas, Insulin

Disqualifiers: Diabetes, Urgent chemotherapy, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 6 months

37 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether metformin, a common diabetes drug, can help treat chronic lymphocytic leukemia (CLL), a type of blood cancer. Researchers believe metformin might combat cancer by lowering insulin levels and blocking certain cancer growth pathways. The trial seeks individuals with CLL whose cancer has returned after treatments like fludarabine or rituxan. Participants should not have diabetes and must be able to eat and drink most of their usual daily meals. As a Phase 2 trial, this research focuses on measuring metformin's effectiveness in an initial, smaller group of people with CLL.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking metformin, sulfonylureas, thiazolidinediones, or insulin. Also, you cannot join if you are less than 30 days from your last CLL treatment.

Is there any evidence suggesting that metformin is likely to be safe for humans?

Research has shown that metformin is usually safe for use. Studies have found that it can lower the risk of certain cancers, including blood cancers like leukemia. In past studies, individuals using metformin for diabetes had a reduced chance of developing blood-related cancers.

Metformin helps the body use insulin more effectively and can directly affect cancer cells. This suggests it might aid in treating certain blood cancers with minimal side effects. Some individuals might experience stomach discomfort, especially at higher doses, but taking metformin with food can alleviate this.

Overall, metformin maintains a strong safety record in both diabetes management and early cancer research. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Metformin is unique because it brings a fresh approach to treating chronic lymphocytic leukemia (CLL) by leveraging its original role as a diabetes medication. Unlike standard treatments like chemotherapy or targeted therapies such as ibrutinib, metformin might impact cancer cells by altering their metabolism, essentially starving them of energy. Researchers are excited because this could offer a less toxic alternative to existing treatments, potentially leading to fewer side effects and improving the quality of life for patients with CLL.

What evidence suggests that metformin might be an effective treatment for chronic lymphocytic leukemia?

Research shows that metformin, which participants in this trial will receive, can disrupt how chronic lymphocytic leukemia (CLL) cells use energy, potentially causing them to die and stop growing. Metformin activates a process that controls cell energy and deactivates another that promotes cell growth. Previous studies have shown that metformin can improve outcomes in various solid tumors, suggesting potential effectiveness for CLL. However, some studies found that metformin did not improve survival rates when used at the start of CLL treatment in people without diabetes. Overall, metformin's dual approach to attacking cancer cells makes it a promising option for further testing in CLL patients. ^{1 6 7 8 9}

Who Is on the Research Team?

Sami Malek, MD

Principal Investigator

University of Michigan Rogel Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-79 with relapsed or untreated chronic lymphocytic leukemia (CLL) who have specific blood cell counts and markers. They must not have diabetes, be taking certain diabetes medications, or require urgent chemotherapy. Participants need to be in stable health without severe heart failure or a history of allergic reactions to metformin.

Inclusion Criteria

My lymph nodes have been swollen for more than 3 months.

My condition worsened after treatment with specific cancer drugs.

I have an untreated del11q mutation.

Exclusion Criteria

I am currently taking medication for diabetes.

Conditions which would increase risk of lactic acidosis including:

I have diabetes with high blood sugar or HgbA1C levels.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive metformin therapy starting at 500 mg daily, escalating to 1000 mg twice a day if tolerated

6 months

Weekly visits for dose escalation in the first 3 weeks, then monthly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Visits every 3 months

Long-term follow-up

Participants are monitored yearly for treatment failure and other outcomes

Yearly

What Are the Treatments Tested in This Trial?

Interventions

• Metformin

Trial Overview The study tests Metformin, commonly used for diabetes, on CLL patients. It explores how Metformin affects cancer cells by improving insulin sensitivity and activating pathways that may inhibit cancer growth. This pilot trial aims to see if it's safe and effective in treating CLL.

How Is the Trial Designed?

Group I: Metformin (Glucophage) Experimental Treatment 1 Intervention

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 already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Glucophage for:

• Type 2 diabetes

Approved in United States as Glucophage for:

• Type 2 diabetes

Approved in Canada as Glucophage for:

• Type 2 diabetes

Approved in Japan as Glucophage for:

• Type 2 diabetes

Approved in China as Glucophage for:

• Type 2 diabetes

Approved in Switzerland as Glucophage for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

Published Research Related to This Trial

Chronic lymphocytic leukaemia (CLL) primarily affects older adults, particularly men, and asymptomatic patients can expect a life expectancy similar to the general population, often requiring only monitoring.

Chlorambucil is the standard treatment for symptomatic CLL, while fludarabine is used if chlorambucil is ineffective; however, combination therapies do not show improved outcomes compared to these single-agent treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic lymphocytic leukaemia: only treat when symptomatic. [2013]

In a phase II pilot study involving 24 patients with chronic lymphocytic leukemia (CLL) who had previously undergone chemotherapy, alemtuzumab demonstrated significant efficacy, with 33% of patients achieving a major response and a median survival time of 35.8 months.

Despite its effectiveness, the treatment was associated with a high incidence of opportunistic infections due to low lymphocyte counts, suggesting that future studies should implement mandatory antimicrobial prophylaxis to enhance patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine. Rai, KR., Freter, CE., Mercier, RJ., et al.[2017]

Subcutaneous alemtuzumab is effective in treating residual disease in chronic lymphocytic leukemia (CLL), with 23 out of 29 evaluable patients responding positively to the treatment after self-administration.

Higher plasma levels of alemtuzumab at the end of treatment were associated with longer response durations, highlighting the importance of monitoring drug levels and minimal residual disease in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Self-administered, subcutaneous alemtuzumab to treat residual disease in patients with chronic lymphocytic leukemia. Wierda, WG., Kipps, TJ., Keating, MJ., et al.[2021]

In a study of 141 patients with chronic lymphocytic leukemia (CLL) treated with venetoclax, the overall response rate was 72%, indicating that venetoclax is an effective treatment option, especially for patients with mutations that typically resist other therapies like ibrutinib.

The treatment was generally well-tolerated, with 85% of patients reaching the maximum recommended dose of 400 mg daily, although some experienced adverse effects such as neutropenia (47.4%) and tumor lysis syndrome (13.4%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world outcomes and management strategies for venetoclax-treated chronic lymphocytic leukemia patients in the United States. Mato, AR., Thompson, M., Allan, JN., et al.[2020]

Recent advancements in treatment options for chronic lymphocytic leukemia (CLL) include novel targeted therapies like obinutuzumab and ofatumomab, which are effective and well-tolerated, especially for elderly patients or those with other health issues.

Ibrutinib and idelalisib show excellent efficacy in CLL, particularly for patients with 17p deletions, while the newly FDA-approved venetoclax offers promising results for those with relapsed or refractory disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanding the armamentarium for chronic lymphocytic leukemia: A review of novel agents in the management of chronic lymphocytic leukemia. Marini, BL., Samanas, L., Perissinotti, AJ.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01750567

NCT01750567 | A Pilot Study of Metformin Therapy in ... A Phase II Pilot Study of Metformin Therapy in Patients With Relapsed Chronic Lymphocytic Leukemia and Untreated CLL Patients With Genomic Deletion

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10873432/

Research Progress on the Use of Metformin in Leukemia ... A recent meta-analysis showed that the long-term use of metformin was associated with a reduction in the incidence of multiple solid tumors [9].

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.e19511

Effect of metformin on survival in CLL and risk stratification ... Prior studies in solid tumors, as well as our own prior research with DLBCL, have shown that Metformin improves outcomes. We sought to ...

4. withpower.com withpower.com/trial/phase-3-leukemia-9-2012-025cc

Metformin for Chronic Lymphocytic Leukemia Research shows that metformin can induce cell death and prevent the growth of chronic lymphocytic leukemia cells by interfering with their energy use and ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT230349

A retrospective analysis of the Roswell Park CLL Database. Results: Metformin at the time of first line treatment was not associated with improved latency or OS compared to patients who were not diabetic, or were ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01750567

A Pilot Study of Metformin Therapy in Patients With ... Patients should have a confirmed diagnosis of chronic lymphocytic leukemia defined as all of the following: ALC > 5000 · Patients should have findings of relapse ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7967492/

Metformin - its anti-cancer effects in hematologic ... Many studies have been published recently confirming the beneficial effects of metformin on leukemic cells under both in vitro and in vivo conditions.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02948283

Metformin Hydrochloride and Ritonavir in Treating Patients ... This pilot clinical trial studies the side effects and best dose of metformin hydrochloride and ritonavir in treating patients with multiple myeloma or ...

9. annsaudimed.net annsaudimed.net/doi/10.5144/0256-4947.2024.126

Metformin and risk of hematological cancers in patients ... The analysis revealed that metformin use in patients with diabetes was significantly associated with a decreased risk of HCs (OR=0.88; 95%CI: 0.79–0.98), with ...