Clinical trial NCT04730258: A Study of CFI-400945 With or Without Azacitidine 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 in Patients With AML, MDS or CMML
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia
Myelodysplastic Syndromes
Chronic Myelomonocytic Leukemia
AML
MDS
CMML
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
Treadwell Tx
Lead sponsor: Treadwell Therapeutics, Inc
Sponsor class: INDUSTRY
First posted: 2021-01-29
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose escalation and expansion for monotherapy and combination arms with azacitidine
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Incidence of treatment emergent AEs
timeFrame: 36 months
measure: Treatment emergent changes in vital signs
timeFrame: 36 months
measure: Treatment emergent changes in clinical laboratory tests
timeFrame: 36 months
measure: Treatment emergent changes in physical examinations, ECOG performance status, electrocardiograms (ECGs), echocardiograms and cardiac troponins
timeFrame: 36 months
Secondary outcomes:
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])
timeFrame: 36 months
measure: Overall response rate (ORR, defined as Complete remission + Marrow CR + Partial remission + Hematologic Improvement (CR + mCR+ PR + HI)
timeFrame: 36 months
measure: The pharmacokinetics of CFI-400945 will be assessed through AUC.
timeFrame: 36 months
measure: To assess the pharmacokinetic profile of CFI-400945 through Cmax.
timeFrame: 36 months
measure: To assess the pharmacokinetic profile of CFI-400945 through T1/2.
timeFrame: 36 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: Louisville
country: United States
facility: Norton Cancer Institute - Saint Matthews
state: Kentucky
city: New York
country: United States
facility: New York Presbyterian Weill Cornell Medical Center
state: New York
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Centre
state: Texas
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
Study officials:
affiliation: The University of Texas MD Anderson Cancer Centre
name: Gautam Borthakur, MD
role: PRINCIPAL_INVESTIGATOR
References: