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
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
Drug | Synonyms | Arms |
---|
CFI-400945 | CFI-400945 fumarate, 945, 400945 | 1A: Monotherapy escalation and expansion |
Azacitidine | | 2A: Combination escalation and expansion |
Decitabine | | 2B: 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
Name | Type | Description | Interventions |
---|
1A: Monotherapy escalation and expansion | Experimental | Dose escalation and expansion arm with CFI-400945 | |
1B: Food Effect | Experimental | Food effect at the recommended phase 2 dose | |
2A: Combination escalation and expansion | Experimental | Dose escalation and expansion arm with CFI-400945 and azacitidine | |
2B: Combination escalation and expansion | Experimental | Dose escalation and expansion arm with CFI-400945 and 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