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

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ClinicalTrials.gov Identifier: NCT04730258
Recruitment Status : Not yet recruiting
First Posted : January 29, 2021
Last Update Posted : May 3, 2021
Sponsor:
Information provided by (Responsible Party):
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 or decitabine

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Myelodysplastic Syndromes Chronic Myelomonocytic Leukemia AML MDS CMML Drug: CFI-400945 Drug: Azacitidine Drug: Decitabine Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose escalation and expansion for monotherapy and combination arms with azacitidine or decitabine
Masking: None (Open Label)
Primary Purpose: Treatment
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 or Decitabine in Patients With AML, MDS or CMML
Estimated Study Start Date : April 2021
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : January 2024


Arm Intervention/treatment
Experimental: 1A: Monotherapy escalation and expansion
Dose escalation and expansion arm with CFI-400945
Drug: 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: 1B: Food Effect
Food effect at the recommended phase 2 dose
Drug: 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
Drug: 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

Drug: Azacitidine
Azacitidine will be given at its labeled dose and schedule

Experimental: 2B: Combination escalation and expansion
Dose escalation and expansion arm with CFI-400945 and decitabine
Drug: 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

Drug: Decitabine
Decitabine will be given at its labeled dose and schedule




Primary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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.


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04730258


Contacts
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Contact: Treadwell Therapeutics Clinical Trials +1-416-455-7510 clinicaltrials@treadwelltx.com

Locations
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United States, California
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
Contact: Brian Jonas, MD       brian.jonas@ucdmc.ucdavis.edu   
Contact: Linh Dang-Chu       ldangchu@ucdavis.edu   
United States, Kentucky
Norton Cancer Institute - Saint Matthews
Louisville, Kentucky, United States, 40207
United States, Texas
The University of Texas MD Anderson Cancer Centre
Houston, Texas, United States, 77030
Contact: Gautam Borthakur       gborthak@mdanderson.org   
Sponsors and Collaborators
Treadwell Therapeutics, Inc
Investigators
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Principal Investigator: Gautam Borthakur, MD The University of Texas MD Anderson Cancer Centre
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Responsible Party: Treadwell Therapeutics, Inc
ClinicalTrials.gov Identifier: NCT04730258    
Other Study ID Numbers: TWT-202
First Posted: January 29, 2021    Key Record Dates
Last Update Posted: May 3, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Treadwell Therapeutics, Inc:
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
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Myelodysplastic-Myeloproliferative Diseases
Azacitidine
Decitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors