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

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Primary Purpose

Status

Not yet recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

CPI 613

Metformin

Blood draws

Bone marrow biopsy

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia, in Relapse

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Wake Forest Baptist Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment - CPI-613 with Metformin

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).

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.

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.

Full Information

NCT ID

NCT05854966

First Posted

May 2, 2023

Last Updated

October 2, 2023

Sponsor

Wake Forest University Health Sciences

Collaborators

National Cancer Institute (NCI), Cornerstone Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT05854966

Brief Title

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

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

November 2023 (Anticipated)

Primary Completion Date

August 2024 (Anticipated)

Study Completion Date

September 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Wake Forest University Health Sciences

Collaborators

National Cancer Institute (NCI), Cornerstone Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

No

Product Manufactured in and Exported from the U.S.

No

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

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.

Masking

None (Open Label)

Allocation

N/A

Enrollment

17 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment - CPI-613 with Metformin

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

CPI 613

Other Intervention Name(s)

Devimistat

Intervention Description

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

Intervention Name(s)

Metformin

Other Intervention Name(s)

Metformin pill

Intervention Description

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

Biological

Intervention Name(s)

Blood draws

Intervention Description

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

Procedure

Intervention Name(s)

Bone marrow biopsy

Intervention Description

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.

Primary Outcome Measure Information:

Title

Number of Participants to Receive at Least One Cycle of Maintenance Therapy - Feasibility

Description

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)

Secondary Outcome Measure Information:

Title

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

Description

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

Title

Overall Survival

Description

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

Title

Number of Reported Adverse Events - Safety

Description

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Study Coodinator

Phone

336-716-5440

Email

bpowell@wakehealth.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bayard Powell, MD

Organizational Affiliation

Wake Forest Baptist Comprehensive Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Wake Forest Baptist Comprehensive Cancer Center

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27157

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Study Coordinator

Phone

336-716-5440

Email

bpowell@wakehealth.edu

First Name & Middle Initial & Last Name & Degree

Bayard Powell, MD

12. IPD Sharing Statement

Plan to Share IPD

No

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

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial