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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04282668
Recruitment Status : Not yet recruiting
First Posted : February 25, 2020
Last Update Posted : February 25, 2020
Sponsor:
Information provided by (Responsible Party):
Astex Pharmaceuticals, Inc.

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: TAS1440 Drug: TAS1440 + ATRA Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Estimated Study Start Date : March 15, 2020
Estimated Primary Completion Date : July 1, 2022
Estimated Study Completion Date : July 1, 2022


Arm Intervention/treatment
Experimental: TAS1440
TAS1440 as a single agent administered once daily (QD) on specific days during each 28-day cycle in Part 1.
Drug: TAS1440
Form: Capsule Route of Administration: Oral

Experimental: TAS1440 + ATRA
TAS1440 administered QD on specific days during each 28-day cycle in combination with ATRA twice daily (BID) in Part 2.
Drug: TAS1440
Form: Capsule Route of Administration: Oral

Drug: TAS1440 + ATRA
Form: Capsule Route of Administration: Oral
Other Names:
  • Tretinoin
  • Vesanoid




Primary Outcome Measures :
  1. Safety: Number of participants with treatment-emergent adverse events (TEAEs) [ Time Frame: Approximately 30 months ]

Secondary Outcome Measures :
  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) [ Time Frame: Approximately 30 months ]
  2. Overall survival: Time from the date of the first dose until death due to any cause [ Time Frame: Approximately 30 months ]
  3. Pharmacokinetic parameter: Area under the curve (AUC) [ Time Frame: Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle) ]
  4. Pharmacokinetic parameter: Maximum plasma concentration (Cmax) [ Time Frame: Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle) ]
  5. Pharmacokinetic parameter: Minimum plasma concentration (Cmin) [ Time Frame: Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle) ]
  6. 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) ]
  7. Pharmacokinetic parameter: Half-life (t1/2) [ Time Frame: Up to Day 8 of Cycle 1 and Cycle 2 (28 days per cycle) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 (CNS) 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 OR high disease burden of blast % of > 50% (in bone marrow or peripheral blood).
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04282668


Contacts
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Contact: James Lowder, MD 925-560-2894 James.Lowder@astx.com

Sponsors and Collaborators
Astex Pharmaceuticals, Inc.
Investigators
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Study Director: James Lowder, MD Astex Pharmaceuticals, Inc.
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Responsible Party: Astex Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04282668    
Other Study ID Numbers: TAS1440-01
First Posted: February 25, 2020    Key Record Dates
Last Update Posted: February 25, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Tretinoin
Antineoplastic Agents
Keratolytic Agents
Dermatologic Agents