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
Overview
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- Treadwell Therapeutics, Inc
- Enrollment
- 72
- Locations
- 9
- Primary Endpoint
- Incidence of treatment emergent AEs
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients must be \>18 years of age
- •For Parts 1A and 1B, the following malignancy types will be included:
- •Relapsed or refractory AML.
- •MDS, after prior hypomethylating agents.
- •CMML, with progressive disease/lack of response after hypomethylating agents
- •For Parts 1A and 1B, Patients may have relapsed or refractory disease.
- •For Parts 2A and 2B, the following malignancy types will be included:
- •Relapsed or Refractory AML.
- •MDS patients should be limited to high risk disease
- •MDS or CMML should be previously untreated and patients with AML may have relapsed or refractory disease;
Exclusion Criteria
- •Patients who have received investigational therapy, radiotherapy, immunotherapy, monoclonal antibodies, or chemotherapy within 14 days or 5 half-lives (whichever is shorter)
- •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
- •Any Grade ≥ 2 persistent non-hematological toxicity related to allogeneic transplant, such as those requiring systemic immunosuppressive therapy.
Arms & Interventions
1A: Monotherapy escalation and expansion
Dose escalation and expansion arm with CFI-400945
Intervention: CFI-400945 (Drug)
2A: Combination escalation and expansion
Dose escalation and expansion arm with CFI-400945 and azacitidine
Intervention: CFI-400945 (Drug)
2A: Combination escalation and expansion
Dose escalation and expansion arm with CFI-400945 and azacitidine
Intervention: Azacitidine (Drug)
Outcomes
Primary Outcomes
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
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.
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.
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.
Secondary Outcomes
- Overall response rate (ORR, defined as Complete remission + Marrow CR + Partial remission + Hematologic Improvement (CR + mCR+ PR + HI)(36 months)
- The pharmacokinetics of CFI-400945 will be assessed through AUC.(36 months)
- Composite Complete Remission Rate, CRc (complete remission + complete remission with incomplete blood count recovery + complete remission with incomplete platelet count recovery [CR + CRi + CRp])(36 months)
- To assess the pharmacokinetic profile of CFI-400945 through T1/2.(36 months)
- To assess the pharmacokinetic profile of CFI-400945 through Cmax.(36 months)