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Study of CFI-400945 Fumarate in Patients With Relapsed or Refractory AML or MDS

Primary Purpose

Acute Myeloid Leukemia, Myelodysplastic Syndromes, Relapsed Cancer

Status
Active
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
CFI-400945 Fumarate
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

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

Inclusion Criteria:

  • 18 years of age or older
  • Relapsed and/or refractory myeloid leukemia (AML) or myelodysplastic syndrome (MDS) that meets certain criteria for prior treatments
  • Have acceptable circulating blasts count
  • Have clinically acceptable laboratory blood and urine test results
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
  • Be able to swallow oral medications
  • Have a life expectancy of 3 months or more
  • Agree to use highly effective means of contraception during a defined period
  • Negative serum pregnancy test before the start of the study drugs
  • Have the ability to understand the requirements of the study, provide written informed consent which includes authorization for release of protected health information, abide by the study restrictions, provide a blood and bone marrow sample for genetic testing and agree to return for the required assessments

Exclusion Criteria:

  • Have received cancer therapies within 14 days or 5 half-lives (whichever is shorter) prior to first dose of study drug or have not recovered from toxicities from prior treatments
  • Not recovered from toxicities related to allogeneic transplant
  • Known active extramedullary central nervous system (CNS) AML
  • Secondary cancer needing therapy with exceptions
  • Known active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection
  • Known significant mental illness or other condition that may affect the ability to follow the requirements of the study
  • Have a chronic infection
  • Have uncontrolled severe hypertension
  • Have symptomatic congestive heart failure
  • Have active angina pectoris or recent myocardial infarction
  • Have chronic atrial fibrillation or unacceptable QTc
  • Have had major surgery within 21 days of starting therapy
  • Have additional uncontrolled serious medical or psychiatric illness
  • Have any medical condition that would affect taking the study drug
  • Receiving treatment with full dose warfarin
  • Receiving treatment with drugs not allowed in this study
  • Women who are pregnant or lactating.

Sites / Locations

  • Juravinski Hospital and Cancer Centre
  • Princess Margaret Cancer Centre

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CFI-400945

Arm Description

CFI-400945 will be given by mouth at 64,96,128,160,192 or 224 mg/day, everyday until intolerable side effects or disease progression.

Outcomes

Primary Outcome Measures

Evaluation of the frequency and severity of treatment-emergent adverse events in patients
This will be done to assess safety and tolerability of CFI-400945 fumarate
Highest tolerated dose of CFI-400945 fumarate
The Maximum Tolerated Dose MTD is defined as the highest dose level that does not lead to unacceptable toxicity in two or more patients in a dosing cohort.
Recommended phase 2 dose of CFI-400945 fumarate
Following completion of dosing of at least 1 cycle for all patients enrolled the Recommended Phase 2 Dose (RP2D) will be determined.It will be based upon the MTD established during dose escalation and its comprehensive outcome

Secondary Outcome Measures

Number of participants with response to treatment
Patients responses will be assess using the International Working Group response criteria for AML and MDS.

Full Information

First Posted
June 12, 2017
Last Updated
September 27, 2023
Sponsor
University Health Network, Toronto
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1. Study Identification

Unique Protocol Identification Number
NCT03187288
Brief Title
Study of CFI-400945 Fumarate in Patients With Relapsed or Refractory AML or MDS
Official Title
An Open-Label, Dose Escalation, Safety and Pharmacokinetic Study of CFI-400945 Fumarate Administered Orally to Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 25, 2018 (Actual)
Primary Completion Date
June 30, 2021 (Actual)
Study Completion Date
December 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a phase 1 study of investigational drug CFI-400945 in patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome. The purpose of this phase 1 study is to see how safe and tolerable the study drug is and to determine the best dose (maximum tolerated dose or recommended phase 2 dose) that can be given in this patient population.
Detailed Description
Participants will be screened prior to the start of the study drug for eligibility. Eligible participants will take CFI-400945 by mouth, once a day, every day of each 28 day cycle. Participants will be asked to keep a study drug diary. While receiving the study drug, participants will have standard tests and procedures done for safety purposes. Procedures for research purposes include bone marrow aspirate and additional blood collection for biomarker research, and additional blood samples for pharmacokinetic research. When participants stop the study drug permanently for any reason, they will be asked to have an End of Treatment Visit and be followed for safety purposes.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Myelodysplastic Syndromes, Relapsed Cancer, Refractory Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CFI-400945
Arm Type
Experimental
Arm Description
CFI-400945 will be given by mouth at 64,96,128,160,192 or 224 mg/day, everyday until intolerable side effects or disease progression.
Intervention Type
Drug
Intervention Name(s)
CFI-400945 Fumarate
Intervention Description
CFI-400945 is an investigational drug that is being look at for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). CFI-400945 is an oral (taken by mouth) drug that blocks Polo-like kinase 4 (PLK4) activity. PLK4 is a protein that is important in regulating cell growth and division and cell death. Many tumors are shown to make too much PLK4. When there is too much PLK4 produced, it is believed to contribute to uncontrolled cancer cell growth and division. Therefore, by blocking this protein from working, it is believed to stop tumors from growing or shrink them.
Primary Outcome Measure Information:
Title
Evaluation of the frequency and severity of treatment-emergent adverse events in patients
Description
This will be done to assess safety and tolerability of CFI-400945 fumarate
Time Frame
5 years
Title
Highest tolerated dose of CFI-400945 fumarate
Description
The Maximum Tolerated Dose MTD is defined as the highest dose level that does not lead to unacceptable toxicity in two or more patients in a dosing cohort.
Time Frame
5 years
Title
Recommended phase 2 dose of CFI-400945 fumarate
Description
Following completion of dosing of at least 1 cycle for all patients enrolled the Recommended Phase 2 Dose (RP2D) will be determined.It will be based upon the MTD established during dose escalation and its comprehensive outcome
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Number of participants with response to treatment
Description
Patients responses will be assess using the International Working Group response criteria for AML and MDS.
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 18 years of age or older Relapsed and/or refractory myeloid leukemia (AML) or myelodysplastic syndrome (MDS) that meets certain criteria for prior treatments Have acceptable circulating blasts count Have clinically acceptable laboratory blood and urine test results Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 Be able to swallow oral medications Have a life expectancy of 3 months or more Agree to use highly effective means of contraception during a defined period Negative serum pregnancy test before the start of the study drugs Have the ability to understand the requirements of the study, provide written informed consent which includes authorization for release of protected health information, abide by the study restrictions, provide a blood and bone marrow sample for genetic testing and agree to return for the required assessments Exclusion Criteria: Have received cancer therapies within 14 days or 5 half-lives (whichever is shorter) prior to first dose of study drug or have not recovered from toxicities from prior treatments Not recovered from toxicities related to allogeneic transplant Known active extramedullary central nervous system (CNS) AML Secondary cancer needing therapy with exceptions Known active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection Known significant mental illness or other condition that may affect the ability to follow the requirements of the study Have a chronic infection Have uncontrolled severe hypertension Have symptomatic congestive heart failure Have active angina pectoris or recent myocardial infarction Have chronic atrial fibrillation or unacceptable QTc Have had major surgery within 21 days of starting therapy Have additional uncontrolled serious medical or psychiatric illness Have any medical condition that would affect taking the study drug Receiving treatment with full dose warfarin Receiving treatment with drugs not allowed in this study Women who are pregnant or lactating.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karen Yee, M.D.
Organizational Affiliation
Princess Margaret Cancer Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Juravinski Hospital and Cancer Centre
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 1C3
Country
Canada
Facility Name
Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study of CFI-400945 Fumarate in Patients With Relapsed or Refractory AML or MDS

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