Metformin+Cytarabine for the Treatment of Relapsed/Refractory AML
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|ClinicalTrials.gov Identifier: NCT01849276|
Recruitment Status : Terminated (Slow accrual)
First Posted : May 8, 2013
Results First Posted : November 13, 2018
Last Update Posted : January 31, 2019
|Condition or disease||Intervention/treatment||Phase|
|Adult Acute Megakaryoblastic Leukemia (M7) Adult Acute Minimally Differentiated Myeloid Leukemia (M0) Adult Acute Monoblastic Leukemia (M5a) Adult Acute Monocytic Leukemia (M5b) Adult Acute Myeloblastic Leukemia With Maturation (M2) Adult Acute Myeloblastic Leukemia Without Maturation (M1) Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Adult Acute Myelomonocytic Leukemia (M4) Adult Erythroleukemia (M6a) Adult Pure Erythroid Leukemia (M6b) Blastic Phase Chronic Myelogenous Leukemia Recurrent Adult Acute Myeloid Leukemia Untreated Adult Acute Myeloid Leukemia||Drug: metformin hydrochloride Drug: cytarabine Other: laboratory biomarker analysis||Phase 1|
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.
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 (Clinical Trial)|
|Actual Enrollment :||2 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Metformin and Cytarabine for the Treatment of Relapsed/Refractory Acute Myeloid Leukemia|
|Actual Study Start Date :||March 11, 2015|
|Actual Primary Completion Date :||January 21, 2016|
|Actual Study Completion Date :||January 21, 2016|
Experimental: Treatment (enzyme inhibitor and chemotherapy)
Patients receive metformin hydrochloride orally twice a day on days 1-15 and cytarabine IV over 3 hours twice on days 4-10.
Drug: metformin hydrochloride
Other Name: Glucophage
Other: laboratory biomarker analysis
- 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. 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.
- 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.
- Bone Marrow and Blood Samples Will be Taken Prior to Study Treatment to Determine Number of Leukemic Progenitor Cells [ Time Frame: At baseline prior to study treatment ]
- Immunoblotting [ Time Frame: At baseline prior to study treatment ]Bone marrow and/or blood samples taken prior to initiation of treatment will be used in Immunoblotting studies to observe enzyme and protein activity.
- Identical Immunoblotting [ Time Frame: At baseline prior to study treatment ]Identical immunoblotting studies may also be performed using blood samples taken prior to start of treatment.
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): NCT01849276
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|Principal Investigator:||Jessica Altman, MD||Northwestern University|