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

NCT05854966 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: WFBCCC 22323P30CA012197
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  After the completion of cycle 1 of maintenance therapy (maintenance cycle is 21 days)

Secondary Outcomes (3)

• Response Rate - Efficacy (Acute Myeloid Leukemia European LeukemiaNet 2022)

  After the completion of cycle 2 (each cycle is 14 days), then every three months up to 12 months

• Overall Survival

  Every 3 months after last dose of study treatment, up to 2 years

• Number of Reported Adverse Events - Safety

  Up to 30 days after last dose of study treatment

Study Arms (1)

Treatment - CPI-613 with Metformin

EXPERIMENTAL

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.

Drug: CPI 613; Drug: Metformin; Biological: Blood draws; Procedure: Bone marrow biopsy

Interventions

CPI 613 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.

Also known as: Devimistat

Treatment - CPI-613 with Metformin

Metformin 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

Also known as: Metformin pill

Treatment - CPI-613 with Metformin

Blood draws 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.

Treatment - CPI-613 with Metformin

Bone marrow biopsy 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.

Treatment - CPI-613 with Metformin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Cancer Institute (NCI): collaborator
• Cornerstone Pharmaceuticals: collaborator

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Sarcoma, Myeloid

Interventions

devimistat; Metformin; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Sarcoma; Neoplasms, Connective and Soft Tissue

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Bayard Powell, MD

  Wake Forest Baptist Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 2, 2023
• First Posted: May 11, 2023
• Study Start: December 1, 2024
• Primary Completion: April 1, 2025
• Study Completion: September 1, 2025
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share