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

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03187288
• Other study ID #: CFI-400945-CL-002
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: May 25, 2018
• Est. completion date: June 30, 2024

Study information

• Verified date: April 2024
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 13
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia
• Refractory Cancer
• Relapsed Cancer

Intervention

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.

Locations

Country	Name	City	State
Canada	Juravinski Hospital and Cancer Centre	Hamilton	Ontario
Canada	Princess Margaret Cancer Centre	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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