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

NCT ID: NCT04282668

Last Updated: 2024-12-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

52 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-03-15

Study Completion Date

2024-02-12

Brief Summary

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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.

Detailed Description

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Conditions

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Acute Myeloid Leukemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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TAS1440

TAS1440 as a single agent administered once daily (QD) on specific days during each 28-day cycle in Part 1.

Group Type EXPERIMENTAL

TAS1440

Intervention Type DRUG

Form: Capsule or Tablet Route of Administration: Oral

TAS1440 + ATRA

TAS1440 administered QD on specific days during each 28-day cycle in combination with ATRA twice daily (BID) in Part 2.

Group Type EXPERIMENTAL

TAS1440 + ATRA

Intervention Type DRUG

Form: Capsule or Tablet Route of Administration: Oral

Interventions

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TAS1440

Form: Capsule or Tablet Route of Administration: Oral

Intervention Type DRUG

TAS1440 + ATRA

Form: Capsule or Tablet Route of Administration: Oral

Intervention Type DRUG

Other Intervention Names

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Tretinoin Vesanoid

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Taiho Oncology, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Arizona Cancer Center Site#127

Tucson, Arizona, United States

Site Status

Norton Cancer Institute Site# 108

Louisville, Kentucky, United States

Site Status

University of Michigan Medical School Site#107

Ann Arbor, Michigan, United States

Site Status

Oregon Health and Science University Site#111

Portland, Oregon, United States

Site Status

Fox Chase Cancer Center Site#112

Philadelphia, Pennsylvania, United States

Site Status

Baylor Scott & White Research Institute Site#110

Dallas, Texas, United States

Site Status

MD Anderson Cancer Center Site#101

Houston, Texas, United States

Site Status

Fred Hutchinson Cancer Research Center Site#105

Seattle, Washington, United States

Site Status

Countries

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United States

Other Identifiers

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TAS1440-01

Identifier Type: -

Identifier Source: org_study_id