The purpose of the study is to determine if metformin in combination with cytarabine is safe and effective. Participants in this research study have acute myeloid leukemia (AML) that has come back after initial treatment or has not gone away with initial therapy.There is evidence that metformin directly kills leukemia cells. Laboratory data have also shown that combinations of metformin with cytarabine are more efficient than each agent alone in killing leukemia cells in the laboratory.
PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose (MTD) of metformin (metformin hydrochloride) in combination with cytarabine in relapsed/refractory AML. II. Define the dose limiting toxicity (DLT) of metformin in combination with cytarabine in relapsed/refractory AML. SECONDARY OBJECTIVES: I. Remission rate. II. Overall survival (OS). III. Disease-free survival (DFS). IV. Length of remission. OUTLINE: This is a dose-escalation study of metformin hydrochloride in combination with Cytarabine. Patients receive metformin hydrochloride orally (PO) twice daily (BID) on days 1-15 and cytarabine intravenously (IV) over 3 hours BID on days 4-10. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
2
Northwestern University
Chicago, Illinois, United States
Evaluate Toxicity by Assessing the Adverse Events of Metformin and Cytarabine
To determine the maximum tolerated dose (MTD) by assessing the adverse events of metformin in combination with cytarabine in evaluating toxicity. Assessments will occur daily during cytarabine administration and at least twice weekly following treatment until blood count recovery.
Time frame: Checked daily during administration of cytarabine and at least 2x weekly following therapy until desired blood counts acheived (maximum 15 days)
Study Treatment Dose Toxicity Will be Evaluated by Measurement of Adverse Events Experienced While on Treatment
Determination of Dose Limiting Toxicity (DLT) as evidenced by adverse events due to toxicity from study treatment. If no DLT is observed, then 3 patients will be enrolled in the next dose escalated cohort. If one DLT is seen in the first 3 patients, then an additional 3 patients will be enrolled at the same dose cohort. If 0-1 in 6 patients experience a DLT this dose will be considered tolerable and the next dose escalated cohort with enroll 3 patients. If 2 or more in 6 patients experience a DLT, the maximum tolerated dose (MTD) will have been exceeded and the next cohort will enroll 3 patients at a reduced dose.
Time frame: Checked daily during administration of cytarabine and at least 2x weekly following therapy until desired blood counts acheived (maximum 15 days)
Remission Rate
Patients will be evaluated for remission status in response to therapy.
Time frame: Every 3 months for 2 years, and then every 6 months for 5 years post-treatment
Overall Survival
Patients will be followed-up with from the initiation of study treatment until progression of disease or for up to 5 years, whichever comes first.
Time frame: Every 3 months for 2 years, and then every 6 months for 5 years post-treatment
Disease-free Survival
Evaluation of Disease-Free Survival will defined as the time from the initiation of study treatment until the time of disease relapse.
Time frame: Every 3 months for 2 years, and then every 6 months for 5 years post-treatment
Length of Remission
Patients will be followed-up with to determine Remission length which is defined as the time from attainment of remission to relapse of disease.
Time frame: From date of remission of disease to date of relapse (maximum of 5 year follow-up)
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