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Acute Myeloid LeukemiaPhase 1NCT04282668

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

A Phase 1 study testing TAS1440 and TAS1440 + ATRA in people with Acute Myeloid Leukemia, run by Taiho Oncology, Inc. at 8 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
TAS1440 and TAS1440 + ATRA
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
8 sitesUnited States
Study dates
15 Mar 2020to 12 Feb 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Have a projected life expectancy of at least 12 weeks and be in stable condition to complete 1 full cycle (4 weeks) of treatment.
  • Have histological confirmation of AML by World Health Organization (WHO) 2016 criteria and who have failed all other available conventional therapies.
  • Have a peripheral blood or bone marrow blast count >5% at the time of enrollment.
  • Have disease that:
  • is refractory to standard induction chemotherapy, including but not limited to anthracycline and cytarabine combination therapy, or
  • has relapsed after anthracycline and cytarabine therapy or stem cell transplant (SCT), or
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  • is refractory to or has relapsed after a front-line regimen containing a hypomethylating agent, alone or in combination.
  • Have an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 1.
  • 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.
  • Have adequate liver function as demonstrated by the following:
  • aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3 × upper limit of normal (ULN)
  • AST and ALT <5 × ULN (if considered due to leukemic organ involvement).
  • 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.

Who cannot join

  • Known clinically active central nervous system leukemia.
  • BCR-ABL-positive leukemia.
  • Diagnosis of acute promyelocytic leukemia (M3 AML or APML or APL).
  • Second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy.
  • Grade 3 or higher graft versus host disease (GVHD), or GVHD requiring treatment with either:
  • a calcineurin inhibitor, or
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  • prednisone more than 5 mg/day (Note: Prednisone at any dose for other indications is allowed).
  • 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.
  • 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.
  • 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.
  • 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).
  • Screening 12-lead echocardiogram with measurable QTc interval (according to either Fridericia's or Bazett's correction) of >480 milliseconds.
  • 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.
  • Non-AML-associated pulmonary disease requiring >2 liters per minute (LPM) oxygen.
  • Proliferative AML with total white blood cells > 20,000/uL
  • Any other condition that puts the participant at an imminent risk of death.
  • Treated with any investigational therapy within 2 weeks of the first dose of study treatment.
  • Inability to swallow oral medication.
  • Known hypersensitivity to ATRA, any of its components, or other retinoids.
  • Known sensitivity to parabens.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites
  • University of Michigan Medical School Site#107

    Ann Arbor, Michigan, 48109

  • Baylor Scott & White Research Institute Site#110

    Dallas, Texas, 75246

  • MD Anderson Cancer Center Site#101

    Houston, Texas, 77030

  • Norton Cancer Institute Site# 108

    Louisville, Kentucky, 40207

  • Fox Chase Cancer Center Site#112

    Philadelphia, Pennsylvania, 19111

  • Oregon Health and Science University Site#111

    Portland, Oregon, 97239

  • Fred Hutchinson Cancer Research Center Site#105

    Seattle, Washington, 98109

  • University of Arizona Cancer Center Site#127

    Tucson, Arizona, 85719

Other trials in United States

About this study

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)

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.

Being tested
TAS1440, TAS1440 + ATRA
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TAS1440Drug

    Form: Capsule or Tablet Route of Administration: Oral

  • TAS1440 + ATRADrug

    Also called Tretinoin, Vesanoid

    Form: Capsule or Tablet Route of Administration: Oral

Study groups in NCT04282668
Study groupRoleWhat they receive
TAS1440ExperimentalTAS1440 as a single agent administered once daily (QD) on specific days during each 28-day cycle in Part 1.
Receives: Drug: TAS1440
TAS1440 + ATRAExperimentalTAS1440 administered QD on specific days during each 28-day cycle in combination with ATRA twice daily (BID) in Part 2.
Receives: Drug: TAS1440 + ATRA

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety: Number of participants with treatment-emergent adverse events (TEAEs)

    Measured: Approximately 30 months

Secondary outcomes (7)
  1. 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)

    Measured: Approximately 30 months

  2. Overall survival: Time from the date of the first dose until death due to any cause

    Measured: Approximately 30 months

  3. Pharmacokinetic parameter: Area under the curve (AUC)

    Measured: Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle)

  4. Pharmacokinetic parameter: Maximum plasma concentration (Cmax)

    Measured: Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle)

  5. Pharmacokinetic parameter: Minimum plasma concentration (Cmin)

    Measured: Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle)

  6. Pharmacokinetic parameter: Time to reach maximum plasma concentration (Tmax)

    Measured: Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle)

  7. Pharmacokinetic parameter: Half-life (t1/2)

    Measured: Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Feb 2020
  2. Study start15 Mar 2020
  3. Primary completion12 Feb 2024
  4. Study completion12 Feb 2024

Why it stopped: The study was terminated due to the changing treatment landscape, difficulty in enrolling eligible participants, and little likelihood of providing meaningful clinical benefit for the participants.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04282668
Sponsor's protocol ID
TAS1440-01
Status last verified
Dec 2024
First submitted
21 Feb 2020
Last updated
9 Dec 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TAS1440 and TAS1440 + ATRA in people with Acute Myeloid Leukemia, run by Taiho Oncology, Inc. at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The study was terminated due to the changing treatment landscape, difficulty in enrolling eligible participants, and little likelihood of providing meaningful clinical benefit for the participants.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety: Number of participants with treatment-emergent adverse events (TEAEs) (time frame: Approximately 30 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2024.

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