A Study of TAS1440 With ATRA in Subjects With r/r AML

Acute Myeloid Leukemia Clinical Trial

Official title:

A Phase 1 Study of Safety, Pharmacokinetics, and Preliminary Activity of TAS1440, as a Single Agent and in Combination With All-Trans Retinoic Acid (ATRA) in Subjects With Relapsed or Refractory (r/r) Acute Myeloid Leukemia (AML)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04282668
• Other study ID #: TAS1440-01
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 15, 2020
• Est. completion date: December 1, 2025

Study information

• Verified date: May 2024
• Source: Astex Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, 2-part, Phase 1 study to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of TAS1440 administered as a single agent and in combination with all-trans retinoic acid (ATRA) in participants with acute myeloid leukemia (AML) who have relapsed or are refractory (r/r) to prior treatment. The study duration is expected to be approximately 30 months.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: December 1, 2025
• Est. primary completion date: December 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Have a projected life expectancy of at least 12 weeks and be in stable condition to complete 1 full cycle (4 weeks) of treatment.

2. Have histological confirmation of AML by World Health Organization (WHO) 2016 criteria and who have failed all other available conventional therapies.

3. Have a peripheral blood or bone marrow blast count >5% at the time of enrollment.

4. Have disease that:

1. is refractory to standard induction chemotherapy, including but not limited to anthracycline and cytarabine combination therapy, or

2. has relapsed after anthracycline and cytarabine therapy or stem cell transplant (SCT), or

3. is refractory to or has relapsed after a front-line regimen containing a hypomethylating agent, alone or in combination.

5. Have an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 1.

6. Have adequate renal function as demonstrated by a serum creatinine =1.5 × upper limit of normal (ULN) or calculated creatinine clearance (by the standard Cockcroft-Gault formula) of =60 mL/min.

7. Have adequate liver function as demonstrated by the following:

1. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3 × upper limit of normal (ULN)

2. AST and ALT <5 × ULN (if considered due to leukemic organ involvement).

8. Women of child-bearing potential (according to recommendations of the Clinical Trial Facilitation Group [CTFG]) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening.

Exclusion Criteria:

1. Known clinically active central nervous system leukemia.

2. BCR-ABL-positive leukemia.

3. Diagnosis of acute promyelocytic leukemia (M3 AML or APML or APL).

4. Second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy.

5. Grade 3 or higher graft versus host disease (GVHD), or GVHD requiring treatment with

either:

1. a calcineurin inhibitor, or

2. prednisone more than 5 mg/day (Note: Prednisone at any dose for other indications is allowed).

6. Total serum bilirubin =1.5 × ULN (except for subjects with Gilbert's Syndrome for whom direct bilirubin is >2.5 × ULN), or liver cirrhosis, or chronic liver disease Child-Pugh Class B or C.

7. Known active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Inactive hepatitis carrier status or low viral hepatitis titer being treated with antivirals is allowed. For subjects considered at risk of viral exposure, serologies should be used to establish negativity.

8. Known significant mental illness or other condition such as active alcohol or other substance abuse or addiction that, in the opinion of the investigator, predisposes the subject to high risk of non-compliance with the protocol.

9. Myocardial impairment of any cause (eg, cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, or congestive heart failure) resulting in heart failure by New York Heart Association (NYHA) Criteria (Class III or IV staging).

10. Screening 12-lead echocardiogram with measurable QTc interval (according to either Fridericia's or Bazett's correction) of >480 milliseconds.

11. Active, uncontrolled infection. Participants with an infection receiving treatment (antibiotic, antifungal, or antiviral treatment) must be afebrile and hemodynamically stable for =72 hours before enrollment.

12. Non-AML-associated pulmonary disease requiring >2 liters per minute (LPM) oxygen.

13. Proliferative AML with total white blood cells > 20,000/uL

14. Any other condition that puts the participant at an imminent risk of death.

15. Treated with any investigational therapy within 2 weeks of the first dose of study treatment.

16. Inability to swallow oral medication.

17. Known hypersensitivity to ATRA, any of its components, or other retinoids.

18. Known sensitivity to parabens.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• TAS1440
Form: Capsule or Tablet Route of Administration: Oral
• TAS1440 + ATRA
Form: Capsule or Tablet Route of Administration: Oral

Locations

Country	Name	City	State
United States	University of Michigan Medical School Site#107	Ann Arbor	Michigan
United States	Baylor Scott & White Research Institute Site#110	Dallas	Texas
United States	MD Anderson Cancer Center Site#101	Houston	Texas
United States	Norton Cancer Institute Site# 108	Louisville	Kentucky
United States	Fox Chase Cancer Center Site#112	Philadelphia	Pennsylvania
United States	Oregon Health and Science University Site#111	Portland	Oregon
United States	Fred Hutchinson Cancer Research Center Site#105	Seattle	Washington
United States	University of Arizona Cancer Center Site#127	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Astex Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: Number of participants with treatment-emergent adverse events (TEAEs)		Approximately 30 months
Secondary	Response rate: Number of participants with complete remission (CR), complete remission with incomplete blood count recovery (CRi), partial remission (PR) and complete remission with partial hematological recovery (CRh)		Approximately 30 months
Secondary	Overall survival: Time from the date of the first dose until death due to any cause		Approximately 30 months
Secondary	Pharmacokinetic parameter: Area under the curve (AUC)		Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle)
Secondary	Pharmacokinetic parameter: Maximum plasma concentration (Cmax)		Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle)
Secondary	Pharmacokinetic parameter: Minimum plasma concentration (Cmin)		Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle)
Secondary	Pharmacokinetic parameter: Time to reach maximum plasma concentration (Tmax)		Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle)
Secondary	Pharmacokinetic parameter: Half-life (t1/2)		Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle)