Clinical Trial: Metformin+Cytarabine for the Treatment of Relapsed/Refractory AML

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase I Study of Metformin and Cytarabine for the Treatment of Relapsed/Refractory Acute Myeloid Leukemia

Brief Summary: 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.

Detailed Summary:

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.


Sponsor: Northwestern University

Current Primary Outcome:

  • Evaluate toxicity by assessing the adverse events of metformin and cytarabine [ Time Frame: Checked daily during administration of cytarabine and at least 2x weekly following therapy until desired blood counts acheived (maximum 15 days) ]
    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.
  • Study treatment dose toxicity will be evaluated by measurement of adverse events experienced while on treatment [ Time Frame: Checked daily during administration of cytarabine and at least 2x weekly following therapy until desired blood counts acheived (maximum 15 days) ]
    Determination of Dose Limiting Toxicity (DLT) as evidenced by adverse events due to toxicity from study treatment


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Remission rate [ Time Frame: Every 3 months for 2 years, and then every 6 months for 5 years post-treatment ]
    Patients will be evaluated for remission status in response to therapy.
  • Overall survival [ Time Frame: Every 3 months for 2 years, and then every 6 months for 5 years post-treatment ]
    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.
  • Disease-free survival [ Time Frame: Every 3 months for 2 years, and then every 6 months for 5 years post-treatment ]
    Evaluation of Disease-Free Survival will defined as the time from the initiation of study treatment until the time of disease relapse.
  • Length of remission [ Time Frame: From date of remission of disease to date of relapse (maximum of 5 year follow-up) ]
    Patients will be followed-up with to determine Remission length which is defined as the time from attainment of remission to relapse of disease.


Original Secondary Outcome: Same as current

Information By: Northwestern University

Dates:
Date Received: May 6, 2013
Date Started: July 2013
Date Completion:
Last Updated: August 31, 2016
Last Verified: August 2016