CPI-613 Given With Metformin in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

NCT ID: NCT05854966

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-31
• Study Completion Date: 2025-09-30

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).

Conditions

Acute Myeloid Leukemia, in Relapse; Acute Myeloid Leukemia Refractory; Granulocytic Sarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment - CPI-613 with Metformin

Induction therapy with CPI-613 and Metformin (ideally 2 hours prior to start of CPI-613 infusions on days 1-5) for two cycles of treatment.

Maintenance therapy with CPI-613 and Metformin (ideally 2 hours prior to start of CPI-613 infusions on days 1-5) until progression, intolerable toxicity of withdrawal of consent.

Group Type: EXPERIMENTAL

CPI 613

Intervention Type: DRUG

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.

Metformin

Intervention Type: DRUG

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

Blood draws

Intervention Type: BIOLOGICAL

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.

Bone marrow biopsy

Intervention Type: PROCEDURE

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.

Interventions

CPI 613

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.

Intervention Type: DRUG

Metformin

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

Intervention Type: DRUG

Blood draws

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.

Intervention Type: BIOLOGICAL

Bone marrow biopsy

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.

Intervention Type: PROCEDURE

Other Intervention Names

Devimistat; Metformin pill

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Cornerstone Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayard Powell, MD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest Baptist Comprehensive Cancer Center

Other Identifiers

P30CA012197

Identifier Type: NIH

Identifier Source: secondary_id

View Link

WFBCCC 22323

Identifier Type: -

Identifier Source: org_study_id