A Study of TAS1553 in Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML) and Other Myeloid Neoplasms

NCT04637009 | Terminated Phase 1 FDA Drug

• 1 other identifier: TAS1553-01
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 10

Brief Summary

This is a Phase 1, 2-part, open-label, multicenter, first-in-human (FIH) study to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of TAS1553 administered orally to participants ≥18 years of age with relapsed or refractory (R/R) acute myeloid leukemia (AML) or other myeloid neoplasms where approved therapies have failed or for whom known life-prolonging therapies are not available. The AML population includes de novo AML, secondary AML, and myelodysplastic syndrome (MDS)-transformed into AML. Other myeloid neoplasms include accelerated phase myeloproliferative neoplasms (MPN), and chronic or accelerated phase MPN-unclassifiable (MPN-U) and MDS-MPN. Blast crisis phase of MPNs are considered secondary AML and will be included in the AML cohort. Part 1 is a multicenter, sequential group treatment feasibility study with 1 treatment arm and no masking (dose escalation). Part 2 is a multicenter, two-stage, multiple group, dose confirmation study with 1 treatment arm and no masking (exploratory dose expansion).

Conditions

Acute Myeloid Leukemia; Myeloproliferative Neoplasm; Myelodysplastic/Myeloproliferative Neoplasm

Keywords

MDS/MPN, unclassifiable in chronic phase; Accelerated phase MPN; Chronic neutrophilic leukemia (CNL), accelerated phase; Polycythemia vera (PV), accelerated phase; Primary myelofibrosis (PMF), accelerated phase; Essential thrombocythemia (ET), accelerated phase; Chronic eosinophilic leukemia, not otherwise specified (NOS), accelerated phase; MPN, unclassifiable; MDS/MPN; Chronic myelomonocytic leukemia (CMML); Atypical chronic myeloid leukemia (aCML), BCR-ABL1-negative; MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T); MDS/MPN, unclassifiable

Outcome Measures

Primary Outcomes (4)

• Safety: Number of participants with treatment-emergent adverse events in Part 1

  Up to 12 months

• Safety: Number of participants with dose-limiting toxicities in Part 1

  Up to 12 months

• Response rate in Cohort 1 (AML): Number of participants with complete response (CR) + complete response with partial hematological recovery (CRh), and with CR + incomplete blood count recovery (CRi) in Part 2

  Up to 33 months

• Response rate in Cohort 2 (other myeloid neoplasms): Number of participants with overall response rate (ORR) of CR + partial response (PR) in Part 2

  Up to 33 months

Secondary Outcomes (12)

• Pharmacokinetic parameter: Area under the curve (AUC)

  At specific timepoints from predose up to Day 8 of Cycle 6 (28 days per cycle)

• Pharmacokinetic parameter: Maximum plasma concentration (Cmax)

  At specific timepoints from predose up to Day 8 of Cycle 6 (28 days per cycle)

• Pharmacokinetic parameter: Minimum plasma concentration (Cmin)

  At specific timepoints from predose up to Day 8 of Cycle 6 (28 days per cycle)

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

  At specific timepoints from predose up to Day 8 of Cycle 6 (28 days per cycle)

• Pharmacokinetic parameter: Half-life (t½)

  At specific timepoints from predose up to Day 8 of Cycle 6 (28 days per cycle)

Study Arms (2)

Part 1 (dose escalation)

EXPERIMENTAL

Oral administration of TAS1553 once daily at specific time points.

Drug: TAS1553

Part 2 (dose expansion)

EXPERIMENTAL

Oral administration of TAS1553 once daily at specific time points.

Drug: TAS1553

Interventions

TAS1553 DRUG

Form: tablet; Route of Administration: oral

Part 1 (dose escalation); Part 2 (dose expansion)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent.
• Participant must be 18 years of age or older, at the time of signing the informed consent.
• Life expectancy of at least 12 weeks as assessed by the investigator.
• Participants with R/R AML or other myeloid neoplasms where approved therapies have failed or for whom known life-prolonging therapies are not available. The AML population includes de novo AML, secondary AML, and MDS transformed into AML. Other myeloid neoplasms include accelerated phase MPN, and chronic or accelerated phase MPN-U and MDS-MPN. Blast crisis phase of MPN, MPN-U, and MDS-MPN are considered secondary AML and will be included in the AML cohort.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Have platelet count ≥10,000/μL (transfusions to achieve this level are allowed).
• Have adequate renal function as demonstrated by a 24-hour urine measured creatinine clearance ≥60 mL/min.
• Adequate hepatic function as evidenced by:
• aspartate aminotransferase (AST) ≤3× upper limit of normal (ULN)
• alanine aminotransferase (ALT) ≤3×ULN
• total bilirubin ≤1.5×ULN.
• Participants must be amenable to serial bone marrow biopsies, peripheral blood sampling, and urine sampling during the study.
• 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.

You may not qualify if:

• Participants who have MPN, MPN-U, or MDS/MPN and display hypoplastic bone marrow and would also not ordinarily benefit from cytoreductive therapy such as hydroxyurea (HU).
• Participants with highly proliferative disease are excluded as follows:
• Part 1/AML: white blood cells (WBC) \>20,000/μL and \>50% blasts in blood. Measures to reduce WBC, such as HU treatment within the last 2 weeks and cytotoxic chemotherapy within the last 4 weeks are not allowed to meet this eligibility criterion.
• Part 1/other myeloid neoplasms: WBC \>20,000/μL. A short course of HU may be used to meet this eligibility criterion, as long as HU is discontinued 96 hours and any encountered drug-related toxicity must be resolved to Grade ≤1 before the first dose of study treatment.
• Part 2/Cohort 1, AML: WBC\>20,000/μL and \>50% blasts in blood. A short course of HU may be used to meet this eligibility criterion, as long as HU is discontinued 96 hours, and any encountered drug-related toxicity must be resolved to Grade ≤1 before the first dose of study treatment.
• Known clinically active central nervous system (CNS) leukemia.
• Diagnosis of BCR-ABL-positive leukemia, acute promyelocytic leukemia (M3 AML or APML), or juvenile myelomonocytic leukemia (JMML).
• Second malignancy requiring active systemic therapy, except breast or prostate cancer stable on or responding to endocrine therapy.
• Ongoing Grade ≥3 Graft Versus Host Disease (GVHD), or any grade GVHD requiring active treatment (for example, calcineurin inhibitors, ≥5mg/day prednisone or other steroid equivalent, or other immunosuppressive agents). (Note: Prednisone at any dose for other indications is allowed).
• Advanced human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection; Inactive hepatitis carrier status and participants with laboratory evidence of no active replication and participants on antiviral medication(s) who have a viral load below limit of detection will be permitted.
• 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 participant to high risk of non-compliance with the protocol.
• Active infection resistant to antibiotics; or non-leukemia-associated pulmonary disease requiring \>2 liters per minute oxygen or any other condition that puts the participant at an imminent risk of death.
• hour urinary protein excretion ≥1g or urinalysis of 2+proteinuria.
• History of, or at risk for, cardiac disease, as evidenced by any of the following conditions:
• Abnormal left ventricular ejection fraction (LVEF; \<50%) on echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan at Screening.

Sponsors & Collaborators

• Astex Pharmaceuticals, Inc.: lead

Study Sites (10)

University of Alabama - Birmingham Comprehensive Cancer Center

Birmingham, Alabama, 35233, United States

Location

HonorHealth Research Institute

Scottsdale, Arizona, 82528, United States

Location

University of Southern California Keck School of Medicine

Los Angeles, California, 90033, United States

Location

Augusta University - Georgia Cancer Center

Augusta, Georgia, 30912, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40241, United States

Location

Weill Cornell Medicine and New York - Presbyterian Hospital

New York, New York, 10065, United States

Location

Cleveland Clinic Taussig Cancer Institute

Cleveland, Ohio, 44195, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Alberta Hospital - Hematology Research

Edmonton, Alberta, T6G 2V2, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2L7, Canada

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Neutrophilic, Chronic; Polycythemia Vera; Primary Myelofibrosis; Thrombocythemia, Essential; Pdgfra-Associated Chronic Eosinophilic Leukemia; Pyloric Stenosis, Hypertrophic; Leukemia, Myelomonocytic, Chronic; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Thrombocytosis

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Blood Coagulation Disorders; Blood Platelet Disorders; Hemorrhagic Disorders; Pyloric Stenosis; Gastric Outlet Obstruction; Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2020
• First Posted: November 19, 2020
• Study Start: December 21, 2020
• Primary Completion: February 20, 2023
• Study Completion: February 20, 2023
• Last Updated: August 2, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); US (8)