Trial Outcomes & Findings for Metformin+Cytarabine for the Treatment of Relapsed/Refractory AML (NCT NCT01849276)

Last Updated: 2019-01-31

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

2 participants

Primary outcome timeframe

Checked daily during administration of cytarabine and at least 2x weekly following therapy until desired blood counts acheived (maximum 15 days)

Results posted on

2019-01-31

Participant Flow

The study opened for accrual July 29, 2013 with an accrual goal of between 19 to 28 participants in a 3 + 3 dose escalation design to find the maximum tolerated dose of metformin in combination with cytarabine. The study was closed permanently on January 21 2016 due to slow accrual.

Participant milestones

Participant milestones
Measure	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. metformin hydrochloride: Given orally cytarabine: Given IV laboratory biomarker analysis: Correlative studies
Registered to the Study STARTED	2
Registered to the Study COMPLETED	2
Registered to the Study NOT COMPLETED	0
Completed Treatment STARTED	2
Completed Treatment COMPLETED	2
Completed Treatment NOT COMPLETED	0
Followed for Survival for 5 Years STARTED	2
Followed for Survival for 5 Years COMPLETED	0
Followed for Survival for 5 Years NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	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. metformin hydrochloride: Given orally cytarabine: Given IV laboratory biomarker analysis: Correlative studies
Followed for Survival for 5 Years Death	1
Followed for Survival for 5 Years Early termination of the study	1

Baseline Characteristics

Metformin+Cytarabine for the Treatment of Relapsed/Refractory AML

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Enzyme Inhibitor and Chemotherapy) n=2 Participants Patients receive metformin hydrochloride orally twice a day on days 1-15 and cytarabine IV over 3 hours twice on days 4-10. metformin hydrochloride: Given orally cytarabine: Given IV laboratory biomarker analysis: Correlative studies
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants

PRIMARY outcome

Timeframe: Checked daily during administration of cytarabine and at least 2x weekly following therapy until desired blood counts acheived (maximum 15 days)

Population: Adverse events that were assessed to be either possibly or unlikely related to treatment on study (i.e. relationship between treatment and adverse event could not be ruled out)

Outcome measures

Outcome measures
Measure	Treatment (Enzyme Inhibitor and Chemotherapy) n=2 Participants Patients receive metformin hydrochloride orally twice a day on days 1-15 and cytarabine IV over 3 hours twice on days 4-10. metformin hydrochloride: Given orally cytarabine: Given IV laboratory biomarker analysis: Correlative studies
Evaluate Toxicity by Assessing the Adverse Events of Metformin and Cytarabine Grade 1	4 Adverse events related to treatment
Evaluate Toxicity by Assessing the Adverse Events of Metformin and Cytarabine Grade 3	2 Adverse events related to treatment
Evaluate Toxicity by Assessing the Adverse Events of Metformin and Cytarabine Grade 4	0 Adverse events related to treatment
Evaluate Toxicity by Assessing the Adverse Events of Metformin and Cytarabine Grade 2	6 Adverse events related to treatment

PRIMARY outcome

Timeframe: Checked daily during administration of cytarabine and at least 2x weekly following therapy until desired blood counts acheived (maximum 15 days)

Population: The study was terminated early due to slow accrual, thus insufficient data was collected to be analysed.

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.