Acute Myeloid LeukemiaPhase 1/2TWT-202NCT04730258
A Study of CFI-400945 With or Without Azacitidine in Patients With AML, MDS or CMML
A Phase 1/2 study testing CFI-400945 and Azacitidine in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by Treadwell Therapeutics, Inc at 9 sites in 3 countries.
Trial summary
The purpose of this study is to test the safety of an investigational drug called CFI-400945 alone and in combination with azacitidine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia
- What is being tested?
- CFI-400945 and Azacitidine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 9 sitesin 3 countries
- Study dates
- 16 Apr 2021to Jan 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 12Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
9 sites in 3 countries.
9 sites in 3 countries
United States6 sites
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
City of Hope
Duarte, California, 91010
The University of Texas MD Anderson Cancer Centre
Houston, Texas, 77030
Norton Cancer Institute - Saint Matthews
Louisville, Kentucky, 40207
New York Presbyterian Weill Cornell Medical Center
New York, New York, 10021
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Canada2 sites
University of Alberta
Edmonton, Alberta, T6G2B7
Princess Margaret Cancer Center
Toronto, Ontario, M5G2C1
About this study
Official title: 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
The purpose of this study is to test the safety of an investigational drug called CFI-400945 alone and in combination with azacitidine.
Read the detailed description
This study will be evaluating the safety and tolerability of CFI-400945 in subjects with Acute Myeloid Leukemia, Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia. The study is designed to build on encouraging data from another study and to obtain further safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) data of CFI-400945.
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, AML, MDS, CMML
- Being tested
- CFI-400945, Azacitidine
- Keywords
- Polo-like kinase 4, PLK4, serine/threonine kinase Polo-like kinase 4, CFI-400945, 945, Polo-Like Kinase 4 inhibitors/antagonists, hematologic malignancies, PLK-4, UHN, University Health Network, Treadwell, Treadwell Therapeutics, Treadwell Tx
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CFI-400945Drug
Also called CFI-400945 fumarate, 945, 400945
The starting dose is 32 mg/day for escalation arms and the recommended starting dose for the expansion arms.
AzacitidineDrug
Azacitidine will be given at its labeled dose and schedule
| Study group | Role | What they receive |
|---|---|---|
| 1A: Monotherapy escalation and expansion | Experimental | Dose escalation and expansion arm with CFI-400945 Receives: Drug: CFI-400945 |
| 2A: Combination escalation and expansion | Experimental | Dose escalation and expansion arm with CFI-400945 and azacitidine Receives: Drug: CFI-400945; Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment emergent AEs
The number of subjects who experience an adverse event that was possibly related to study drug
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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])
Response rate will be summarized by dose cohort and overall using the percent of patients in patient with AML
Measured: 36 months
Overall response rate (ORR, defined as Complete remission + Marrow CR + Partial remission + Hematologic Improvement (CR + mCR+ PR + HI)
Response rate will be summarized by dose cohort and overall using the percent of patients in patients with MDS, CMML
Measured: 36 months
The pharmacokinetics of CFI-400945 will be assessed through AUC.
Area under the plasma concentration (AUC) versus time curve from time 0 to time of least measurable concentration tabulated by dose group.
Measured: 36 months
To assess the pharmacokinetic profile of CFI-400945 through Cmax.
Cmax will be assessed through the maximum measured plasma concentration occurring at Tmax tabulated by dose group.
Measured: 36 months
To assess the pharmacokinetic profile of CFI-400945 through T1/2.
Elimination half life will be calculated and tabulated by dose group.
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2021
- Study start16 Apr 2021
- Primary completionJan 2026 (estimated)
- Study completionJan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Dose escalation and expansion for monotherapy and combination arms with azacitidine
- Masking
- None (open label)
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Treadwell Therapeutics, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gautam Borthakur, MD, Principal investigator, The University of Texas MD Anderson Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04730258
- Sponsor's protocol ID
- TWT-202
- Acronym
- TWT-202
- Status last verified
- May 2025
- First submitted
- 25 Jan 2021
- Last updated
- 18 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: 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.
Publications
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.
PubMed 38114624
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04730258
- Acronym / sponsor ID
- TWT-202 / TWT-202
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, AML, MDS, CMML
- Keywords
- Polo-like kinase 4, PLK4, serine/threonine kinase Polo-like kinase 4, CFI-400945, 945, Polo-Like Kinase 4 inhibitors/antagonists, hematologic malignancies, PLK-4
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- Treadwell Therapeutics, IncIndustry (pharma, biotech, devices)
- Study start
- 16 Apr 2021 (actual)
- Primary completion
- Jan 2026 (estimated)
- Study completion
- Jan 2026 (estimated)
- First posted
- 29 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test the safety of an investigational drug called CFI-400945 alone and in combination with azacitidine.
Detailed description
This study will be evaluating the safety and tolerability of CFI-400945 in subjects with Acute Myeloid Leukemia, Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia. The study is designed to build on encouraging data from another study and to obtain further safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) data of CFI-400945.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Dose escalation and expansion for monotherapy and combination arms with azacitidine
| Arm | Type | Receives |
|---|---|---|
| 1A: Monotherapy escalation and expansion | Experimental | Drug: CFI-400945Dose escalation and expansion arm with CFI-400945 |
| 2A: Combination escalation and expansion | Experimental | Drug: CFI-400945, Drug: AzacitidineDose escalation and expansion arm with CFI-400945 and azacitidine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients must be >18 years of age
- For Parts 1A and 1B, the following malignancy types will be included:
- For Parts 1A and 1B, Patients may have relapsed or refractory disease.
- For Parts 2A and 2B, the following malignancy types will be included:
- Have clinically acceptable laboratory screening results (i.e., clinical chemistry, hematology, and urinalysis) within certain limits per protocol.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CFI-400945Also: CFI-400945 fumarate, 945, 400945The starting dose is 32 mg/day for escalation arms and the recommended starting dose for the expansion arms. | Drug | 1A: Monotherapy escalation and expansion, 2A: Combination escalation and expansion |
| AzacitidineAzacitidine will be given at its labeled dose and schedule | Drug | 2A: Combination escalation and expansion |
Primary outcome
Incidence of treatment emergent AEs
Time frame: 36 months
The number of subjects who experience an adverse event that was possibly related to study drug
Treatment emergent changes in vital signs
Time frame: 36 months
The number of subjects who experience changes in blood pressure, heart rate, respiratory rate, body temperature that was possibly related to study drug.
Treatment emergent changes in clinical laboratory tests
Time frame: 36 months
The number of subjects who experience a change in laboratory parameters that was possibly related to study drug.
Treatment emergent changes in physical examinations, ECOG performance status, electrocardiograms (ECGs), echocardiograms and cardiac troponins
Time frame: 36 months
The number of subjects who experience changes in physical examinations, performance status, ECG, troponins that were possibly related to study drug.
5 secondary outcomes
Composite Complete Remission Rate, CRc (complete remission + complete remission with incomplete blood count recovery + complete remission with incomplete platelet count recovery [CR + CRi + CRp])
Time frame: 36 months
Overall response rate (ORR, defined as Complete remission + Marrow CR + Partial remission + Hematologic Improvement (CR + mCR+ PR + HI)
Time frame: 36 months
The pharmacokinetics of CFI-400945 will be assessed through AUC.
Time frame: 36 months
To assess the pharmacokinetic profile of CFI-400945 through Cmax.
Time frame: 36 months
To assess the pharmacokinetic profile of CFI-400945 through T1/2.
Time frame: 36 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2025.
- Derived from this study: PubMed 38114624Murphy 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.
- Individual participant dataSharing planned: No. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gautam Borthakur, MD principal investigator
The University of Texas MD Anderson Cancer Centre
9 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CFI-400945 and Azacitidine in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by Treadwell Therapeutics, Inc at 9 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 18 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Canada, Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment emergent AEs (time frame: 36 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04730258, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2025.