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)

Taiho Oncology, Inc.8 sites in 1 country52 target enrollmentMarch 15, 2020

ConditionsAcute Myeloid Leukemia

InterventionsTAS1440 TAS1440 + ATRA

DrugsTAS1440 TAS1440 + ATRA

Overview

Phase: Phase 1
Intervention: TAS1440
Conditions: Acute Myeloid Leukemia
Sponsor: Taiho Oncology, Inc.
Enrollment: 52
Locations: 8
Primary Endpoint: Safety: Number of participants with treatment-emergent adverse events (TEAEs)
Status: Terminated
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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.

Registry

clinicaltrials.gov

Start Date

March 15, 2020

End Date

February 12, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Taiho Oncology, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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
•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
•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:

Exclusion Criteria

•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
•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.

Arms & Interventions

TAS1440

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

Intervention: TAS1440

TAS1440 + ATRA

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

Intervention: TAS1440 + ATRA

Outcomes

Primary Outcomes

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

Time Frame: Approximately 30 months

Secondary Outcomes

Pharmacokinetic parameter: Half-life (t1/2)(Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle))
Overall survival: Time from the date of the first dose until death due to any cause(Approximately 30 months)
Pharmacokinetic parameter: Maximum plasma concentration (Cmax)(Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle))
Pharmacokinetic parameter: Minimum plasma concentration (Cmin)(Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle))
Pharmacokinetic parameter: Time to reach maximum plasma concentration (Tmax)(Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle))
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)
Pharmacokinetic parameter: Area under the curve (AUC)(Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle))