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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Relapsed Cancer; Refractory Cancer
• Intervention / Treatment: Drug: CFI-400945 Fumarate

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 1C3
      • Juravinski Hospital and Cancer Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CFI-400945; 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.

Drug: CFI-400945 Fumarate; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	5 years
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.	5 years
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	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with response to treatment	Patients responses will be assess using the International Working Group response criteria for AML and MDS.	5 years

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Karen Yee, M.D., Princess Margaret Cancer Centre

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2018
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: June 12, 2017
• First Submitted That Met QC Criteria: June 12, 2017
• First Posted (Actual): June 14, 2017

Study Record Updates

• Last Update Posted (Actual): August 22, 2024
• Last Update Submitted That Met QC Criteria: August 21, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia
• Other Study ID Numbers: CFI-400945-CL-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No