Immediate Allogeneic Hematopoietic Stem Cell Transplantation Versus Re-treatment for Patients With High-Risk Acute Myeloid Leukemia

Официальное название

Immediate Allogeneic Hematopoietic Stem Cell Transplantation Versus Re-treatment for Patients With High-Risk Acute Myeloid Leukemia: a Randomised, Open-label, Phase 2 Clinical Trial.

Обзор

This study aims to investigate whether immediate HSCT for patients with high-risk AML and intermediate-risk AML who have not achieved complete remission (CR) after their first induction therapy is non-inferior to re-treatment with chemotherapy.

Подробное описание

1. Disease control group: patients proceeded to allogeneic HSCT as soon as possible. Patients were allowed to receive low-dose chemotherapy that is not intended for the purpose of achieving a second remission. 2. Retreatment group: Receive a second course of anti-leukemic treatment prior to allogeneic HSCT. The anti-leukemic treatment regimen will be determined based on the genetic mutation status. Patients without targetable mutations will receive a combination of BCL-2 inhibitors and demethylating agents as salvage chemotherapy. Patients with targetable mutations will receive appropriate targeted therapy (e.g., FLT3 inhibitors, IDH inhibitors).

For patients who have already received targeted therapy during induction treatment, the researchers may choose the treatment regimen based on the individual patient's condition.

Вмешательства

• Другое ImmediateAllogeneic Hematopoietic Stem Cell Transplantation
  patients proceeded to allogeneic HSCT as soon as possible. Patients were allowed to receive low-dose chemotherapy that is not intended for the purpose of achieving a second remission.
• Другое Retreatment
  Receive a second course of anti-leukemic treatment prior to allogeneic HSCT. The anti-leukemic treatment regimen will be determined based on the genetic mutation status. Patients without targetable mutations will receive a combination of BCL-2 inhibitors and demethylating agents as salvage chemotherapy. Patients with targetable mutations will receive appropriate targeted therapy (e.g., FLT3 inhibitors, IDH inhibitors).

Первичные конечные точки

• treatment success [Срок оценки: day 56 after allogeneic HCT]

Вторичные конечные точки (7)

• Cumulative Incidences of Allogeneic HSCT [Срок оценки: HSCT rates at 4,8,16, and 24 weeks]
• Incidence of Complete Remission from Randomisation [Срок оценки: Date of first documented CR or CRi or CRchim Death before CR/CRi/CRchim not achieve a CR or CRi by six months]
• Overall survival after HCT [Срок оценки: Death]
• Event-free survival after HCT [Срок оценки: death before relapse, relapse (both, hematological or molecular), and failure to achieve a CR at final remission assessment]
• Leukemia-free survival from day 56 after alloHCT for patients who met the primary endpoint [Срок оценки: day 56]
• Rate of MRD Negative from Day 56 after HSCT [Срок оценки: day 56]
• 7. Overall Survival from Randomization: Measured from the start of randomization, with the primary event being death. [Срок оценки: Death]

Критерии участия

Критерии включения

• AML patients aged ≥ 18 years.
• High-risk AML patients according to the 2022 ELN standards who received one cycle of induction therapy.
• Requires allogeneic hematopoietic stem cell transplantation (including HLA-matched or mismatched allogeneic HSCT and unrelated donor transplant).
• KPS score greater than 60.
• Informed consent must be signed before the start of the study procedures; if it is detrimental to the patient's condition for them to sign, the consent may be signed by a legal guardian or immediate family member.

Критерии исключения

• Acute promyelocytic leukemia.
• Patient has received more than 440 mg/m2 daunorubicin equivalents. The cumulative dose is calculated by summing up isotoxic daunorubicin-equivalents for daunorubicin, doxorubicin, epirubicin, idarubicin and mitoxantrone. The conversion factors are derived from the comparison of the respective maximum doses. The conversion factor is 1 for daunorubicin, 1 for doxorubicin, 0.6 for epirubicin, 4.6 for idarubicin, and 2.7 for mitoxantrone (see worksheet for calculation).
• Severe organ dysfunction, defined as:

1\) Left ventricular ejection fraction <50%. 2) Patients who receive supplementary continuous oxygen. 3) Serum bilirubin >1.5 x ULN (if not considered Gilbert-Syndrome) or ASAT/ALAT >5 x ULN.

4\) Estimated Glomerular Filtration Rate (GFR) < 50 ml/min, where: Estimated GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine)-1.154 x (age in years)-0.203 x (0.742 if patient is female) x (1.212 if patient is black) 4. History of allogeneic transplantation. 5. Manifestation of AML in the Central Nervous System. 6. Pregnant or breastfeeding women.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 4 центра

• Hebei Medical University Second Hospital — Shijiazhuang
• Zhengzhou University First Affiliated Hospital — Чжэнчжоу
• The 960th Hospital of the Joint Service Support Force of the Chinese People's Liberation A — Цзинань
• People's Liberation Army The General Hospital of Western Theater Command — Чэнду

Идентификаторы

NCT: NCT06643195 · IIT2024063

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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