Description:
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.
Title
- Brief Title: A Study of TAS1440 With ATRA in Subjects With r/r AML
- 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 IDs
- ORG STUDY ID:
TAS1440-01
- NCT ID:
NCT04282668
Conditions
Interventions
Drug | Synonyms | Arms |
---|
TAS1440 | | TAS1440 |
TAS1440 + ATRA | Tretinoin, Vesanoid | TAS1440 + ATRA |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
TAS1440 | Experimental | TAS1440 as a single agent administered once daily (QD) on specific days during each 28-day cycle in Part 1. | |
TAS1440 + ATRA | Experimental | TAS1440 administered QD on specific days during each 28-day cycle in combination with ATRA twice daily (BID) in Part 2. | |
Eligibility Criteria
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Safety: Number of participants with treatment-emergent adverse events (TEAEs) |
Time Frame: | Approximately 30 months |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | 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) |
Time Frame: | Approximately 30 months |
Safety Issue: | |
Description: | |
Measure: | Overall survival: Time from the date of the first dose until death due to any cause |
Time Frame: | Approximately 30 months |
Safety Issue: | |
Description: | |
Measure: | Pharmacokinetic parameter: Area under the curve (AUC) |
Time Frame: | Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle) |
Safety Issue: | |
Description: | |
Measure: | Pharmacokinetic parameter: Maximum plasma concentration (Cmax) |
Time Frame: | Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle) |
Safety Issue: | |
Description: | |
Measure: | Pharmacokinetic parameter: Minimum plasma concentration (Cmin) |
Time Frame: | Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle) |
Safety Issue: | |
Description: | |
Measure: | Pharmacokinetic parameter: Time to reach maximum plasma concentration (Tmax) |
Time Frame: | Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle) |
Safety Issue: | |
Description: | |
Measure: | Pharmacokinetic parameter: Half-life (t1/2) |
Time Frame: | Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle) |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Astex Pharmaceuticals, Inc. |
Last Updated
August 31, 2021