A Study of CFI-400945 With or Without Azacitidine in Patients With AML, MDS or CMML (TWT-202)

February 2, 2024 updated by: Treadwell Therapeutics, Inc

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.

Study Overview

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 Type

Interventional

Enrollment (Estimated)

72

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Alberta
    • Ontario
      • Toronto, Ontario, Canada, M5G2C1
        • Recruiting
        • Princess Margaret Cancer Center
        • Contact:
          • Karen Yee
        • Contact:
      • Hong Kong, Hong Kong
        • Recruiting
        • Queen Mary Hospital
        • Contact:
        • Contact:
          • Anskar Leung
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
        • Contact:
          • Paul Koller
        • Contact:
      • Sacramento, California, United States, 95817
    • Kentucky
      • Louisville, Kentucky, United States, 40207
        • Completed
        • Norton Cancer Institute - Saint Matthews
    • New York
      • New York, New York, United States, 10021
        • Recruiting
        • New York Presbyterian Weill Cornell Medical Center
        • Contact:
          • Gail Roboz
        • Contact:
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • The Ohio State University Comprehensive Cancer Center
        • Contact:
          • Alice Mims
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas MD Anderson Cancer Centre
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1A: Monotherapy escalation and expansion
Dose escalation and expansion arm with CFI-400945
The starting dose is 32 mg/day for escalation arms and the recommended starting dose for the expansion arms.
Other Names:
  • CFI-400945 fumarate
  • 945
  • 400945
Experimental: 2A: Combination escalation and expansion
Dose escalation and expansion arm with CFI-400945 and azacitidine
The starting dose is 32 mg/day for escalation arms and the recommended starting dose for the expansion arms.
Other Names:
  • CFI-400945 fumarate
  • 945
  • 400945
Azacitidine will be given at its labeled dose and schedule

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
36 months
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.
36 months
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.
36 months
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.
36 months

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Gautam Borthakur, MD, The University of Texas MD Anderson Cancer Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 16, 2021

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

January 1, 2026

Study Registration Dates

First Submitted

January 25, 2021

First Submitted That Met QC Criteria

January 25, 2021

First Posted (Actual)

January 29, 2021

Study Record Updates

Last Update Posted (Estimated)

February 5, 2024

Last Update Submitted That Met QC Criteria

February 2, 2024

Last Verified

November 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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