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

Sponsor

Treadwell Therapeutics, Inc (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04730258

Collaborator

(none)

Enrollment

Locations

Arms

32.5

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

Anticipated 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 decitabineDose 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

Actual Study Start Date :

Apr 16, 2021

Anticipated Primary Completion Date :

Jan 1, 2024

Anticipated Study Completion Date :

Jan 1, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Incidence of treatment emergent AEs [36 months]
The number of subjects who experience an adverse event that was possibly related to study drug
Treatment emergent changes in vital signs [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 [36 months]
The number of subjects who experience a change in laboratory parameters that was possibly related to study drug.
Treatment emergent changes in physical examinations, ECOG performance status, electrocardiograms (ECGs), echocardiograms and cardiac troponins [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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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;
Have clinically acceptable laboratory screening results (i.e., clinical chemistry, hematology, and urinalysis) within certain limits per protocol.
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

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 1.
Any Grade ≥ 2 persistent non-hematological toxicity related to allogeneic transplant, such as those requiring systemic immunosuppressive therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
3	Norton Cancer Institute - Saint Matthews	Louisville	Kentucky	United States	40207
4	New York Presbyterian Weill Cornell Medical Center	New York	New York	United States	10021
5	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
6	The University of Texas MD Anderson Cancer Centre	Houston	Texas	United States	77030
7	University of Alberta	Edmonton	Alberta	Canada	T6G2B7
8	Princess Margaret Cancer Center	Toronto	Ontario	Canada	M5G2C1