A Study for Participants Who Participated in Prior Clinical Studies of ASTX727 (Standard Dose)

Официальное название

An Open-Label, Multicenter, Extension Study for Subjects Who Participated in Prior Clinical Studies of ASTX727 (Standard Dose)

Обзор

Extension study to provide ongoing long-term treatment with ASTX727 for participants who were benefitting from ASTX727 treatment in a previous Taiho (formerly Astex)-sponsored clinical study of ASTX727 (including, but not limited to ASTX727-01 \[NCT02103478\], ASTX727-02 \[NCT03306264\], ASTX727-04 \[NCT03813186\]), ASTX727-06 \[NCT04093570\] food effect substudy, ASTX727-17 \[NCT04953897\], and ASTX727-18 \[NCT04953910\] to obtain long-term safety information. The purpose of the Food Effect Substudy was to evaluate the pharmacokinetics (PK) and safety of decitabine and cedazuridine when ASTX727 was given under fed (high-calorie/high-fat meal or low-calorie/low-fat meal) versus fasted conditions. Food Effect Substudy has now completed.

Подробное описание

Main Extension Study: Participants will attend clinic visits on Day 1 of each 28-day cycle to undergo study procedures and to be given ASTX727 tablets for Days 1-5 of that dose cycle. Participants should continue to receive the same ASTX727 dose and regimen they were receiving in the last cycle of the parent study in which they were originally enrolled. Subsequent treatment delays and/or dose reductions are at the discretion of the investigator as guided by the dose adjustment guidelines of the parent study protocol.

Food Effect Substudy: Participants received ASTX727 once daily on Days 1 through 5 followed by a 23-day treatment-free period in a 28-day cycle (Cycle 1). Participants received either a high-calorie, high-fat breakfast meal (Arm A) or a low-calorie/low-fat breakfast meal (Arm B) predose on Day 4. Participants in Arms A and B received ASTX727 on Days 1, 2, 3, and 5 in the fasted condition. Participants may continue treatment with ASTX727 in Cycle 2 onwards in the ASTX727-06 study at the Investigator's discretion, where they continued to receive ASTX727. This substudy consists of a 21-day Screening Period, a 1-cycle (28 days) Treatment Period, and a 30-day (+7 days) Safety Follow-up Period (only if the participant discontinues from the ASTX727-06 food effect substudy and does not continue to receive ASTX727 in the ASTX727-06 study).

Вмешательства

• Препарат ASTX727
  ASTX727 film-coated, immediate-release FDC tablets

Первичные конечные точки

• Main Extension Study: Safety: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) [Срок оценки: From date of transition into this extension study until 30 days following the last dose, up to approximately 2 years]
• Food Effect Substudy: AUC0-last: Area Under the Plasma Concentration-time Curve From Time Zero to Last Concentration Measured of Decitabine in the Fasted and Fed State [Срок оценки: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 ( up to 28 days)]
• Food Effect Substudy: AUC0-last: Area Under the Plasma Concentration-time Curve From Time Zero to Last Concentration Measured of Cedazuridine in the Fasted and Fed State [Срок оценки: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days)]
• Food Effect Substudy: AUC0-last: Area Under the Plasma Concentration-time Curve From Time Zero to Last Concentration Measured of Cedazuridine-epimer in the Fasted and Fed State [Срок оценки: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days)]
• Food Effect Substudy: AUC0-8h: Area Under the Concentration-time Curve From Time Zero to 8 Hours of Decitabine in the Fasted and Fed State [Срок оценки: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days)]
• Food Effect Substudy: AUC0-8h: Area Under the Concentration-time Curve From Time Zero to 8 Hours of Cedazuridine in the Fasted and Fed State [Срок оценки: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days)]
• Food Effect Substudy: AUC0-8h: Area Under the Concentration-time Curve From Time Zero to 8 Hours of Cedazuridine-epimer in the Fasted and Fed State [Срок оценки: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days)]
• Food Effect Substudy: AUC0-24h: Area Under the Concentration-time Curve From Time Zero to 24 Hours of Decitabine in the Fasted and Fed State [Срок оценки: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days)]
• Food Effect Substudy: AUC0-24h: Area Under the Concentration-time Curve From Time Zero to 24 Hours of Cedazuridine in the Fasted and Fed State [Срок оценки: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days)]
• Food Effect Substudy: AUC0-24h: Area Under the Concentration-time Curve From Time Zero to 24 Hours of Cedazuridine-epimer in the Fasted and Fed State [Срок оценки: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days)]

Вторичные конечные точки (2)

• Food Effect Substudy: Percentage of Participants with Treatment Emergent Adverse Events (TEAEs), by Severity [Срок оценки: From first dose of study drug up to 30 days after the last dose (Up to approximately 65 days)]
• Food Effect Substudy: Percentage of Participants with Clinically Significant Abnormal Laboratory Values [Срок оценки: From Day 1 up to Day 28 in Cycle 1 (Up to 28 days)]

Критерии участия

Inclusion Criteria for the Main Extension Study:

Participants must fulfill all of the following inclusion criteria:

• Previous participation in a Taiho (formerly Astex)-sponsored ASTX727 clinical trial (including, but not limited to studies ASTX727-01, ASTX727-02, and ASTX727-04, , ASTX727-17, and ASTX727-18, and the food effect substudy of ASTX727-06) in which the participant was treated with ASTX727 and was still on active treatment with ASTX727 at the time of study completion as determined by Taiho.
• Participant is considered to be benefitting from ASTX727 treatment in the opinion of the treating investigator at the time of parent study completion (Participants must not be withdrawn from the parent study until eligibility for this study is confirmed).
• Participant is able to understand and comply with the study procedures and understands the risks involved in the study.
• Participant provides legally effective informed consent before undergoing any study-specific procedure.
• Women of childbearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of childbearing potential must agree to practice 1 highly effective contraceptive methods of birth control during the study and for 6 months after the last dose of study treatment, agree not to donate eggs for the purpose of reproduction during this period and must agree not to become pregnant for 6 months after completing treatment; men with female partners of childbearing potential must agree to practice 2 highly effective contraceptive measures and must agree not to father a child while receiving ASTX727 and for at least 3 months after completing ASTX727 treatment.

Inclusion Criteria for the Food Effect Substudy:

• Participants must have a confirmed diagnosis of-

i. Myelodysplastic syndromes (MDS) including all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia \[CMML\])), and participants with MDS International Prognostic Scoring System (IPSS) int-1, int-2, or high-risk MD.

ii. Acute myeloid leukemia (AML), as diagnosed according to the 2016 World Health Organization (WHO) guidelines on acute leukemia, of any subtype except M3 (acute promyelocytic leukemia), who are not candidates for intensive chemotherapy, including participants receiving hypomethylating agent (HMA) treatment, who have a confirmed diagnosis and a prior confirmatory bone marrow report. Participants who are currently receiving HMA treatment must complete the ongoing (at the time of Screening) treatment cycle before enrolling in this study; timing of start of treatment cycle with ASTX727 is at the principal investigator's discretion.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Adequate organ function defined as follows:

• Hepatic: Total bilirubin ≤1.5 × upper limit of normal (ULN); aspartate aminotransferase/serum glutamic-oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamic-pyruvic transaminase (ALT/SGPT) ≤5 × ULN.
• Renal: Calculated creatinine clearance ≥60 mL/min.

Exclusion Criterion for the Main Extension Study:

1\. Any participant who, in the opinion of the investigator, may have other conditions, organ dysfunction, or for whom safety data from parent study participation suggests the risks of continuing treatment with ASTX727 may outweigh the benefits.

Exclusion Criteria for the Food Effect Substudy:

• Participants with known or suspected hypersensitivity to decitabine, cedazuridine, or any of the excipients in the ASTX727 tablets.
• Poor medical risk because of other conditions such as uncontrolled systemic diseases or active uncontrolled infections.
• Life-threatening illness, medical condition or organ system dysfunction, or other reasons including laboratory abnormalities, which, in the Investigator's opinion, could compromise the participant's safety, interfere with the absorption or metabolism of decitabine + cedazuridine or compromise the integrity of the study outcomes.
• Prior gastric surgery for ulcer disease, weight loss, etc, that would impair normal motility or absorption.
• Second malignancy currently requiring active chemotherapy. To clarify, participants with breast or prostate cancer stable on or responding to endocrine therapy, are eligible.
• Known history of human immunodeficiency virus or known seropositive for hepatitis C virus or hepatitis B virus.
• Active uncontrolled gastric or duodenal ulcer.
• Participants with acute promyelocytic leukemia.
• Prior cytotoxic chemotherapy for AML except for hydroxyurea to control high white blood cell (WBC) counts.
• Treated with any investigational drug or therapy within 2 weeks of study treatment, or 5 half-lives, whichever is longer, before the protocol-defined first dose of study treatment, or ongoing clinically significant AEs from previous treatment with investigational drug or therapy.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 21 центр

• Compassionate Care Research Group — Fountain Valley
• Boca Raton Clinical Research — Plantation
• The University of Chicago Medical Center — Chicago
• The Sidney Kimmel Comprehensive Cancer Center at John Hopkins — Baltimore
• Cancer and Hematology Centers for Western Michigan — Grand Rapids
• Mayo - Rochester — Rochester
• Hackensack Medical Center - 06 FE Study — Hackensack
• Hackensack Medical Center — Hackensack
• … и ещё 13 центров

Канада · 5 центров

• University of Alberta Hospital — Edmonton
• QEII Health Sciences Centre — Nova Scotia
• The Ottawa Hosptial — Ottawa
• Sunnybrook Health Sciences Centre — Toronto
• Princess Margaret Cancer Center — Toronto

Испания · 5 центров

• Hospital Universitari Arnau de Vilanova — Lleida
• Clínica Universidad de Navarra - Madrid — Madrid
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Clínico Universitario Virgen de la Arrixaca — Murcia
• Hospital Universitario La Fe — Valencia

Армения · 4 центра

• Erebuni Medical Center — Yerevan
• Hematology Center After Prof. R. Yeolyan (Adult Blood Disorders) — Yerevan
• Hematology Center After Prof. R. Yeolyan (Clinic of Adults Oncology) — Yerevan
• National Center of Oncology Named After V.A. Fanarjyan — Yerevan

Австрия · 2 центра

• Wiener Gesundheitsverbund - Klinik Hietzing 06 FE Study — Vienna
• Wiener Gesundheitsverbund - Klinik Hietzing 06 Study — Vienna

Германия · 2 центра

• Städtisches Klinikum Braunschweig — Braunschweig
• Universitätsklinikum Schleswig-Holstein - Campus Lübeck — Lübeck

Румыния · 2 центра

• Institutul Oncologic Bucuresti - Prof. Dr. Alexandru Trestioreanu — Bucharest
• Institutul Oncologic Prof. Dr. Ion Chiricuta — Cluj-Napoca

Болгария · 1 центр

• Specialized Hospital for Active Treatment of Hematological Disease EAD — Sofia

Франция · 1 центр

• Hôpital Emile Muller — Mulhouse

Венгрия · 1 центр

• Debreceni Egyetem Klinikai Kozpont, Belgyogyszati Klinika, B epulet, Hematologia — Debrecen

Италия · 1 центр

• Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico — Milan

Польша · 1 центр

• Centrum Badań Klinicznych Piotr Napora Lekarze Sp. p. — Wroclaw

Словакия · 1 центр

• Summit Clinical Research s.r.o — Bratislava

Идентификаторы

NCT: NCT04093570 · ASTX727-06 · 2024-516293-29-01 · 2018-003942-18

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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