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

NCT ID: NCT04730258

Last Updated: 2025-05-18

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-16
• Study Completion Date: 2026-01-31

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.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; AML; MDS; CMML

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1A: Monotherapy escalation and expansion

Dose escalation and expansion arm with CFI-400945

Group Type: EXPERIMENTAL

CFI-400945

Intervention Type: DRUG

The starting dose is 32 mg/day for escalation arms and the recommended starting dose for the expansion arms.

2A: Combination escalation and expansion

Dose escalation and expansion arm with CFI-400945 and azacitidine

Group Type: EXPERIMENTAL

CFI-400945

Intervention Type: DRUG

The starting dose is 32 mg/day for escalation arms and the recommended starting dose for the expansion arms.

Azacitidine

Intervention Type: DRUG

Azacitidine will be given at its labeled dose and schedule

Interventions

CFI-400945

The starting dose is 32 mg/day for escalation arms and the recommended starting dose for the expansion arms.

Intervention Type: DRUG

Azacitidine

Azacitidine will be given at its labeled dose and schedule

Intervention Type: DRUG

Other Intervention Names

CFI-400945 fumarate; 945; 400945

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Treadwell Therapeutics, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gautam Borthakur, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas MD Anderson Cancer Centre

Locations

City of Hope

Duarte, California, United States

University of California Davis Comprehensive Cancer Center

Sacramento, 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

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

Countries

United States; Canada; Hong Kong

References

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.

Reference Type: DERIVED

PMID: 38114624 (View on PubMed)

Other Identifiers

TWT-202

Identifier Type: -

Identifier Source: org_study_id