The purpose of this research study is to find out what effects (the good and bad) the combination treatment of metformin and CPI-613 has in treating participants with acute myeloid leukemia or granulocytic sarcoma that has either returned after treatment or did not respond to treatment.
Primary Objective: To establish the feasibility of delivering the combination of CPI-613 and metformin in patients with relapsed or refractory acute myeloid leukemia (AML). Secondary Objectives: To determine the response rate of CPI-613 and metformin in relapsed or refractory AML defined as Complete remission (CR) + Complete remission with incomplete count recovery (CRi) + Morphologic Leukemia-Free State (MLFS). * To determine the overall survival of patients with relapsed or refractory AML treated with CPI-613 and metformin. * To determine the safety of CPI-613 and metformin in patients with relapsed or refractory acute myeloid leukemia (AML).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
For INDUCTION therapy (14 day cycles): Devimistat (CPI-613) 2,500mg/m2, days 1-5, 14-day cycles for cycles 1 and 2 only. For MAINTENANCE therapy (21 day cycles): Devimistat (CPI-613) 2,500mg/m2, days 1-5, 21-day cycles until progression, intolerable toxicity or withdrawal of consent.
For INDUCTION therapy (14 day cycles): Metformin 500 mg daily (taken with meals), days 1-2 for cycle 1 only. Metformin 500 mg twice daily (taken with meals), days 3-14 for cycle 1 only. Metformin 1,000 mg daily (taken with meals), days 1-2 for cycle 2 only. Metformin 1,000 mg twice daily (taken with meals) days 3-4 for cycle 2 only. For MAINTENANCE therapy (21 day cycles): Metformin 1,000 mg twice daily (taken with meals) days 1-21 until progression, intolerable toxicity or withdrawal of consent
Number of Participants to Receive at Least One Cycle of Maintenance Therapy - Feasibility
Feasibility is defined as the ability to deliver at least 1 cycle of maintenance therapy in 50% or more of patients who complete induction therapy.
Time frame: After the completion of cycle 1 of maintenance therapy (maintenance cycle is 21 days)
Response Rate - Efficacy (Acute Myeloid Leukemia European LeukemiaNet 2022)
Efficacy will be assessed in the first 9 evaluable participants using a Simon's two-stage design to examine efficacy in terms of response where response is defined as: * Complete remission (CR) (Bone marrow blasts, 5%; absence of circulating blasts; absence of extramedullary disease; ANC ≤ 1.0 × 109/L (1,000/μL); plate) or * Complete remission with incomplete count recovery (CRi) (All CR criteria except for residual neutropenia \< 1.0 × 109/L (1,000/μL) or thrombocytopenia \< 100 × 109/L (100,000/μL) or * Morphologically leukemia free state (MLFS) (Bone marrow blasts \< 5%; absence of circulating blasts; absence of extramedullary disease; no hematologic recovery required).
Time frame: After the completion of cycle 2 (each cycle is 14 days), then every three months up to 12 months
Overall Survival
Overall survival is calculated in days from date of study treatment initiation to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
Time frame: Every 3 months after last dose of study treatment, up to 2 years
Number of Reported Adverse Events - Safety
Safety will be evaluated by describing the nature and frequency of adverse events as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: Up to 30 days after last dose of study treatment
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In the first induction cycle ONLY, extra blood will be withdrawn on day 1 before and after treatment with CPI-613 research purposes. Additional blood draws on days 2-5 to test blood before receiving CPI-613 to make sure participants are healthy enough to receive CPI-613.
After the second induction cycle participants will have a bone marrow biopsy. After this biopsy, participants will have other bone marrow biopsies every 3 months for the next year. After the first year, participants may have a bone marrow biopsy if the treating physician feels it is necessary.