Venetoclax Plus Hypomethylating Agents and Subcutaneous Cytarabine for CEBPA-Mutated AML

Официальное название

Prospective Multicenter Clinical Study of Venetoclax Combined With Hypomethylating Agents and Subcutaneous Cytarabine in Induction Therapy for CEBPA-Mutated Acute Myeloid Leukemia

Обзор

The goal of this clinical trial is to learn if a treatment combination-venetoclax plus hypomethylating agents (like azacitidine or decitabine) and low-dose cytarabine-works to treat adults with newly diagnosed CEBPA-mutated acute myeloid leukemia (AML) who can't tolerate intensive chemotherapy. It will also check how safe this treatment combination is and explore how the disease might change if it comes back. The main questions it aims to answer are: 1. How well does this treatment combination prevent the disease from coming back (relapse-free survival)? 2. What percentage of participants achieve a good response (complete remission or complete remission with incomplete blood cell recovery) after 2 treatment cycles? 3. What percentage of participants have no detectable remaining leukemia cells (measurable residual disease, MRD) after treatment? What side effects do participants have, and how serious are these side effects? Participants will: 1. First, go through a 2-cycle "induction phase": Take venetoclax by mouth (100mg on day 1, 200mg on day 2, 400mg from day 3 to day 28), get hypomethylating agents (azacitidine injected under the skin or decitabine injected into a vein), and low-dose cytarabine (injected under the skin) as planned. 2. If they respond well to induction treatment, move to a "consolidation phase" and receive at least 4 more cycles of the same treatment combination. 3. Have regular check-ups during treatment (like blood tests, bone marrow tests, and heart checks) to monitor treatment response and side effects. 4. Be followed up for 2 years after treatment ends to check if the disease comes back and their overall health.

Вмешательства

• Препарат Venetoclax + Hypomethylating Agents + Low-Dose Cytarabine for CEBPA-Mutated AML (Unfit Patients)
  1. Induction Therapy (2 Cycles in Total) All medications are administered in a 28-day cycle; the second cycle is given regardless of the response to the first cycle. Medication Generic Name Dosage Form Dosage Administration Frequency Duration per Cycle Venetoclax Oral tablets 100 mg on Day 1; 200 mg on Day 2; 400 mg from Day 3 to Day 28 Once daily (oral) Days 1-28 Azacitidine (alternative to decitabine) Injectable 75 mg/m² per day Once daily (subcutaneous injection) Days 1-7 Decitabine (alte

Первичные конечные точки

• Relapse-Free Survival (RFS) [Срок оценки: From date of achieving CR/CRi until first occurrence of disease relapse or death from any cause, assessed up to 48 months (2 years after the last patient has been enrolled into the study).]

Вторичные конечные точки (5)

• Composite Remission Rate after 2 Induction Cycles [Срок оценки: Proportion of participants who achieve CR or CRi after completing 2 cycles of induction therapy. (Each cycle is 28 days)]
• Minimal Residual Disease (MRD) Negativity Rate [Срок оценки: 21 to 28 days after the end of every treatment]
• Duration of Remission (DOR) [Срок оценки: From date of achieving CR/CRi until first occurrence of disease relapse or death from any cause, assessed up to 60 months.]
• Relapse Rate [Срок оценки: Proportion of participants who experience disease relapse after achieving CR/CRi, assessed up to 48 months (2 years after the last patient has been enrolled into the study).]
• Overall Survival (OS) [Срок оценки: From start of treatment until death from any cause, assessed up to 48 months (2 years after the last patient has been enrolled into the study).]

Критерии участия

Критерии включения

• Patients can participate in this study only if they meet all the following enrollment criteria:

• Aged over 18 years, male, or female who is neither pregnant nor lactating;
• Newly diagnosed acute myeloid leukemia (AML) with CEBPA mutation;
• ECOG performance status ≤ Grade 3;
• Capable of understanding and willing to participate in the study, and able to sign the informed consent form;
• Patients are judged as "unfit" according to the Ferrara criteria. A patient is considered "unfit" if they meet at least one of the following criteria:

• Advanced age: > 75 years old;

• Presence of severe underlying comorbidities involving the heart, lungs, kidneys, or liver; ③ Presence of active infection unresponsive to anti-infective treatment;

• Presence of cognitive impairment; ⑤ Poor performance status (persistent ECOG score ≥ Grade 3); ⑥ Other comorbidities judged by the investigator to make the patient unfit for intensive chemotherapy.

Критерии исключения

• Patients are not suitable for participating in this study if they meet any of the following exclusion criteria:

• Pregnant or lactating women;
• Previous receipt of chemotherapy or targeted drug therapy for leukemia before the study treatment (except oral hydroxyurea used to reduce white blood cell count and/or leukapheresis);
• As known to the participant and the investigator, the participant may be unable to complete all study visits or procedures required by the study protocol (including follow-up visits) and/or unable to comply with the required study procedures;
• Other conditions judged by the investigator to make the patient unfit for participating in this study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital of Soochow University — Сучжоу

Идентификаторы

NCT: NCT07451912 · SZAML-05

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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