A Study of CFI-400945 With or Without Azacitidine in Patients With AML, MDS or CMML

Acute Myeloid Leukemia Clinical Trial

— TWT-202  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04730258
• Other study ID #: TWT-202
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 16, 2021
• Est. completion date: January 2026

Study information

• Verified date: April 2024
• Source: Treadwell Therapeutics, Inc
• Contact: Treadwell Therapeutics Clinical Trials
• Phone: +1-416-455-7510
• Email: clinicaltrials[@]treadwelltx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: January 2026
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients must be >18 years of age

2. For Parts 1A and 1B, the following malignancy types will be included:

1. Relapsed or refractory AML.

2. MDS, after prior hypomethylating agents.

3. CMML, with progressive disease/lack of response after hypomethylating agents For Parts 1A and 1B, Patients may have relapsed or refractory disease.

3. For Parts 2A and 2B, the following malignancy types will be included:

1. Relapsed or Refractory AML.

2. MDS patients should be limited to high risk disease

3. MDS or CMML should be previously untreated and patients with AML may have relapsed or refractory disease;

4. Have clinically acceptable laboratory screening results (i.e., clinical chemistry, hematology, and urinalysis) within certain limits per protocol.

5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion Criteria:

1. Patients who have received investigational therapy, radiotherapy, immunotherapy, monoclonal antibodies, or chemotherapy within 14 days or 5 half-lives (whichever is shorter)

2. 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.

3. Any Grade = 2 persistent non-hematological toxicity related to allogeneic transplant, such as those requiring systemic immunosuppressive therapy.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• AML
• Chronic Myelomonocytic Leukemia
• CMML
• Leukemia
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• MDS
• Myelodysplastic Syndromes

Intervention

Drug:
• CFI-400945
The starting dose is 32 mg/day for escalation arms and the recommended starting dose for the expansion arms.
• Azacitidine
Azacitidine will be given at its labeled dose and schedule

Locations

Country	Name	City	State
Canada	University of Alberta	Edmonton	Alberta
Canada	Princess Margaret Cancer Center	Toronto	Ontario
Hong Kong	Queen Mary Hospital	Hong Kong
United States	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	City of Hope	Duarte	California
United States	The University of Texas MD Anderson Cancer Centre	Houston	Texas
United States	Norton Cancer Institute - Saint Matthews	Louisville	Kentucky
United States	New York Presbyterian Weill Cornell Medical Center	New York	New York
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
Treadwell Therapeutics, Inc

Countries where clinical trial is conducted

United States,  Canada,  Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment emergent AEs	The number of subjects who experience an adverse event that was possibly related to study drug	36 months
Primary	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
Primary	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
Primary	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	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	36 months
Secondary	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	36 months
Secondary	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.	36 months
Secondary	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.	36 months
Secondary	To assess the pharmacokinetic profile of CFI-400945 through T1/2.	Elimination half life will be calculated and tabulated by dose group.	36 months