Clinical Trials /

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

NCT04730258

Description:

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

Related Conditions:
  • Acute Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of CFI-400945 With or Without Azacitidine or Decitabine in Patients With AML, MDS or CMML
  • 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

Clinical Trial IDs

  • ORG STUDY ID: TWT-202
  • NCT ID: NCT04730258

Conditions

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

Interventions

DrugSynonymsArms
CFI-400945CFI-400945 fumarate, 945, 4009451A: Monotherapy escalation and expansion
Azacitidine2A: Combination escalation and expansion
Decitabine2B: Combination escalation and expansion

Purpose

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

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.
    

Trial Arms

NameTypeDescriptionInterventions
1A: Monotherapy escalation and expansionExperimentalDose escalation and expansion arm with CFI-400945
  • CFI-400945
1B: Food EffectExperimentalFood effect at the recommended phase 2 dose
  • CFI-400945
2A: Combination escalation and expansionExperimentalDose escalation and expansion arm with CFI-400945 and azacitidine
  • CFI-400945
  • Azacitidine
2B: Combination escalation and expansionExperimentalDose escalation and expansion arm with CFI-400945 and decitabine
  • CFI-400945
  • Decitabine

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of treatment emergent AEs
Time Frame:36 months
Safety Issue:
Description:The number of subjects who experience an adverse event that was possibly related to study drug

Secondary Outcome Measures

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

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Treadwell Therapeutics, Inc

Trial Keywords

  • 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

Last Updated

June 14, 2021