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

Phase 1

Active, not recruiting

• Conditions: AML; MDS; Myelodysplastic Syndromes; CMML; Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia
• Interventions: Drug: CFI-400945; Drug: Azacitidine

• Registration Number: NCT04730258
• Lead Sponsor: Treadwell Therapeutics, Inc

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.

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 Timeline

• Study First Submitted: 2021-01-25
• Study First Submitted QC: 2021-01-25
• Study First Posted: 2021-01-29
• Study Start: 2021-04-16
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-16
• Last Update Posted: 2025-05-18
• Primary Completion: 2026-01
• Study Completion: 2026-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 72

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
2A: Combination escalation and expansion	Azacitidine	Dose escalation and expansion arm with CFI-400945 and azacitidine
1A: Monotherapy escalation and expansion	CFI-400945	Dose escalation and expansion arm with CFI-400945
2A: Combination escalation and expansion	CFI-400945	Dose escalation and expansion arm with CFI-400945 and azacitidine

Primary Outcome Measures

Name	Time	Method
Incidence of treatment emergent AEs	36 months	The number of subjects who experience an adverse event that was possibly related to study drug
Treatment emergent changes in physical examinations, ECOG performance status, electrocardiograms (ECGs), echocardiograms and cardiac troponins	36 months	The number of subjects who experience changes in physical examinations, performance status, ECG, troponins that were possibly related to study drug.
Treatment emergent changes in vital signs	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	36 months	The number of subjects who experience a change in laboratory parameters that was possibly related to study drug.

Secondary Outcome Measures

Name	Time	Method
Overall response rate (ORR, defined as Complete remission + Marrow CR + Partial remission + Hematologic Improvement (CR + mCR+ PR + HI)	36 months	Response rate will be summarized by dose cohort and overall using the percent of patients in patients with MDS, CMML
The pharmacokinetics of CFI-400945 will be assessed through AUC.	36 months	Area under the plasma concentration (AUC) versus time curve from time 0 to time of least measurable concentration tabulated by dose group.
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	Response rate will be summarized by dose cohort and overall using the percent of patients in patient with AML
To assess the pharmacokinetic profile of CFI-400945 through T1/2.	36 months	Elimination half life will be calculated and tabulated by dose group.
To assess the pharmacokinetic profile of CFI-400945 through Cmax.	36 months	Cmax will be assessed through the maximum measured plasma concentration occurring at Tmax tabulated by dose group.

Trial Locations

Locations (9)

City of Hope; 🇺🇸 Duarte, California, United States

Norton Cancer Institute - Saint Matthews; 🇺🇸 Louisville, Kentucky, United States

New York Presbyterian Weill Cornell Medical Center; 🇺🇸 New York, New York, United States

The Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States

University of California Davis Comprehensive Cancer Center; 🇺🇸 Sacramento, California, United States

The University of Texas MD Anderson Cancer Centre; 🇺🇸 Houston, Texas, United States

University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

Princess Margaret Cancer Center; 🇨🇦 Toronto, Ontario, Canada

Queen Mary Hospital; 🇭🇰 Hong Kong, Hong Kong