Clinical trial NCT05854966: CPI-613 Given With Metformin in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)
Official title: An Open Label, Pilot Phase II Study to Evaluate the Feasibility and Efficacy of CPI-613 Given With Metformin in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Acute Myeloid Leukemia, in Relapse
Acute Myeloid Leukemia Refractory
Granulocytic Sarcoma
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Cornerstone Pharmaceuticals
First posted: 2023-05-11
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a Phase II, Simon's two-stage study evaluating the feasibility and effectiveness of combination CPI-613 and metformin in relapsed or refractory acute myeloid leukemia. The first stage will consist of 9 evaluable patients. If the study continues to stage 2, a total of 17 evaluable patients will be enrolled.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

* Patients must have histologically or cytologically documented relapsed and/or refractory Acute Myeloid Leukemia or granulocytic sarcoma.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 3.
* Must be ≥ 18 years of age.
* Persons of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device \[IUD\], oral contraceptive or double barrier device), and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation.
* Persons who are having sexual relationships in which their partner may become pregnant must practice effective contraceptive methods during the study treatment and for 60 days after the last dose of study treatment, unless documentation of infertility exists.
* Mentally competent, ability to understand and willingness to sign the informed consent form.
* Patients with persisting, non-hematologic, non-infectious toxicities from prior treatment must be ≤ Grade 2 and must be documented as such.
* Laboratory values ≤ 2 weeks prior to the start of study treatment must be the following:
* Aspartate aminotransferase \[AST/SGOT\] ≤ 5x upper normal limit \[UNL\],
* Alanine aminotransferase \[ALT/SGPT\] ≤ 5x UNL
* Bilirubin ≤ 3x UNL
* Albumin ≥ 2.0 g/dL or ≥ 20 g/L
* Serum creatinine ≤ 2.0 mg/dL
* Presence of central venous catheter or willing to have central venous access placed.

Exclusion Criteria:

* Patients with active central nervous system (CNS) or epidural tumor.
* Pregnant persons, or persons of child-bearing potential not using reliable means of contraception (because the teratogenic potential of CPI-613 is unknown).
* Breastfeeding individuals because the potential of excretion of CPI-613 into breast milk. (Note: Breastfeeding individuals are excluded because the effects of CPI-613 on a nursing child are unknown).
* Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patient.
* Unwilling or unable to follow protocol requirements.
* Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication within the past 1 week prior to initiation of CPI-613 treatment with the following exceptions:
* The use of Hydrea or any targeted oral agent is allowed up to the day before initiation of treatment.

Primary outcomes:
measure: Number of Participants to Receive at Least One Cycle of Maintenance Therapy - Feasibility
timeFrame: After the completion of cycle 1 of maintenance therapy (maintenance cycle is 21 days)
Secondary outcomes:
measure: Response Rate - Efficacy (Acute Myeloid Leukemia European LeukemiaNet 2022)
timeFrame: After the completion of cycle 2 (each cycle is 14 days), then every three months up to 12 months
measure: Overall Survival
timeFrame: Every 3 months after last dose of study treatment, up to 2 years
measure: Number of Reported Adverse Events - Safety
timeFrame: Up to 30 days after last dose of study treatment
Other outcomes:
Locations:
Study officials:
affiliation: Wake Forest Baptist Comprehensive Cancer Center
name: Bayard Powell, MD
role: PRINCIPAL_INVESTIGATOR
References: