A Study of CFI-400945 With or Without Azacitidine in Patients With AML, MDS or CMML
TWT-202
Phase 1b/2 Clinical Study of the Safety, Tolerability, and Pharmacokinetic and Pharmacodynamic Profiles of CFI-400945 as a Single Agent or in Combination With Azacitidine in Patients With AML, MDS or CMML
1 other identifier
interventional
72
3 countries
9
Brief Summary
The purpose of this study is to test the safety of an investigational drug called CFI-400945 alone and in combination with azacitidine.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Apr 2021
Longer than P75 for phase_1
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 25, 2021
CompletedFirst Posted
Study publicly available on registry
January 29, 2021
CompletedStudy Start
First participant enrolled
April 16, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2026
CompletedMay 18, 2025
May 1, 2025
4.7 years
January 25, 2021
May 16, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Incidence of treatment emergent AEs
The number of subjects who experience an adverse event that was possibly related to study drug
36 months
Treatment emergent changes in vital signs
The number of subjects who experience changes in blood pressure, heart rate, respiratory rate, body temperature that was possibly related to study drug.
36 months
Treatment emergent changes in clinical laboratory tests
The number of subjects who experience a change in laboratory parameters that was possibly related to study drug.
36 months
Treatment emergent changes in physical examinations, ECOG performance status, electrocardiograms (ECGs), echocardiograms and cardiac troponins
The number of subjects who experience changes in physical examinations, performance status, ECG, troponins that were possibly related to study drug.
36 months
Secondary Outcomes (5)
Composite Complete Remission Rate, CRc (complete remission + complete remission with incomplete blood count recovery + complete remission with incomplete platelet count recovery [CR + CRi + CRp])
36 months
Overall response rate (ORR, defined as Complete remission + Marrow CR + Partial remission + Hematologic Improvement (CR + mCR+ PR + HI)
36 months
The pharmacokinetics of CFI-400945 will be assessed through AUC.
36 months
To assess the pharmacokinetic profile of CFI-400945 through Cmax.
36 months
To assess the pharmacokinetic profile of CFI-400945 through T1/2.
36 months
Study Arms (2)
1A: Monotherapy escalation and expansion
EXPERIMENTALDose escalation and expansion arm with CFI-400945
2A: Combination escalation and expansion
EXPERIMENTALDose escalation and expansion arm with CFI-400945 and azacitidine
Interventions
The starting dose is 32 mg/day for escalation arms and the recommended starting dose for the expansion arms.
Azacitidine will be given at its labeled dose and schedule
Eligibility Criteria
You may qualify if:
- Patients must be \>18 years of age
- For Parts 1A and 1B, the following malignancy types will be included:
- Relapsed or refractory AML.
- MDS, after prior hypomethylating agents.
- CMML, with progressive disease/lack of response after hypomethylating agents
- For Parts 1A and 1B, Patients may have relapsed or refractory disease.
- For Parts 2A and 2B, the following malignancy types will be included:
- Relapsed or Refractory AML.
- MDS patients should be limited to high risk disease
- MDS or CMML should be previously untreated and patients with AML may have relapsed or refractory disease;
- Have clinically acceptable laboratory screening results (i.e., clinical chemistry, hematology, and urinalysis) within certain limits per protocol.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
You may not qualify if:
- Patients who have received investigational therapy, radiotherapy, immunotherapy, monoclonal antibodies, or chemotherapy within 14 days or 5 half-lives (whichever is shorter)
- Allogeneic or autologous transplant for AML with infusion of stem cells within 90 days before Cycle 1 Day 1, or on active immunosuppressive therapy for graft-versus-host disease (GVHD) or GVHD prophylaxis within 2 weeks of Cycle 1 Day 1.
- Any Grade ≥ 2 persistent non-hematological toxicity related to allogeneic transplant, such as those requiring systemic immunosuppressive therapy.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (9)
City of Hope
Duarte, California, 91010, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Norton Cancer Institute - Saint Matthews
Louisville, Kentucky, 40207, United States
New York Presbyterian Weill Cornell Medical Center
New York, New York, 10021, United States
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
The University of Texas MD Anderson Cancer Centre
Houston, Texas, 77030, United States
University of Alberta
Edmonton, Alberta, T6G2B7, Canada
Princess Margaret Cancer Center
Toronto, Ontario, M5G2C1, Canada
Queen Mary Hospital
Hong Kong, Hong Kong
Related Publications (1)
Murphy T, Mason JM, Leber B, Bray MR, Chan SM, Gupta V, Khalaf D, Maze D, McNamara CJ, Schimmer AD, Schuh AC, Sibai H, Trus M, Valiquette D, Martin K, Nguyen L, Li X, Mak TW, Minden MD, Yee KWL. Preclinical characterization and clinical trial of CFI-400945, a polo-like kinase 4 inhibitor, in patients with relapsed/refractory acute myeloid leukemia and higher-risk myelodysplastic neoplasms. Leukemia. 2024 Mar;38(3):502-512. doi: 10.1038/s41375-023-02110-9. Epub 2023 Dec 19.
PMID: 38114624DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Gautam Borthakur, MD
The University of Texas MD Anderson Cancer Centre
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 25, 2021
First Posted
January 29, 2021
Study Start
April 16, 2021
Primary Completion
January 1, 2026
Study Completion
January 1, 2026
Last Updated
May 18, 2025
Record last verified: 2025-05
Data Sharing
- IPD Sharing
- Will not share
It is too early to determine whether we will make IPD available - we do not yet have a process written on this. Field will be updated once our policy / process is written.