A Phase 2 Study of Bcl-2 Inhibitor Combined With Azacitidine for Newly Diagnosed Mixed Phenotype Acute Leukemia
A Prospective, Open-Label, Single-Arm, Two-Cohort Phase 2 Clinical Study to Evaluate the Efficacy and Safety of Bcl-2 Inhibitor Combined With Azacitidine in the Treatment of Newly Diagnosed Mixed Phenotype Acute Leukemia
This is a prospective, open-label, single-arm, two-cohort Phase 2 clinical study designed to evaluate the efficacy and safety of Bcl-2 Inhibitor combined with azacitidine (with blinatumomab added in B/myeloid subtype) in patients with newly diagnosed mixed phenotype acute leukemia (MPAL). Eligible subjects are divided into two cohorts based on immunophenotype: Cohort A (T/Myeloid MPAL) receives Bcl-2 Inhibitor + azacitidine, and Cohort B (B/Myeloid MPAL) receives Bcl-2 Inhibitor + azacitidine + blinatumomab. The treatment cycle is 28 days, with the primary efficacy endpoint assessed after 2 cycles of induction therapy. Patients who achieve CRc will undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) following 2 to 3 cycles of consolidation therapy.The total enrollment period is 24 months, and all subjects will be followed up for at least 24 months from the first day of the first cycle (C1D1).
The primary objective is to evaluate the composite complete response (CRc) rate after 2 cycles of induction therapy , and the secondary objectives include evaluating measurable residual disease (MRD) negativity rate, bridge-to-allogeneic hematopoietic stem cell transplantation (allo-HSCT) rate in first complete response (CR1), overall survival(OS),Event-Free Survival(EFS),Relapse-Free Survival(RFS) and Safety.
Обзор исследования
Статус
Вмешательство/лечение
Тип исследования
Регистрация (Оцененный)
Фаза
- Фаза 2
Контакты и местонахождение
Контакты исследования
- Имя: Jing Lu Doctor
- Номер телефона: 86+0512-67781137
- Электронная почта: gloriajlu@163.com
Места учебы
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Jiangsu
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Suzhou, Jiangsu, Китай, 215000
- The First Affiliated Hospital of Soochow University
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
- Ребенок
- Взрослый
- Пожилой взрослый
Принимает здоровых добровольцев
Описание
Inclusion Criteria:
- Aged 16 to 70 years old
- Newly diagnosed MPAL confirmed by the 2022 WHO/ICC classification criteria for hematopoietic and lymphoid neoplasms
- Previously untreated; use of glucocorticoids or hydroxyurea for ≤7 days to control tumor burden before enrollment is allowed, no other systemic anti-leukemia therapy
- ECOG performance status score 0-3
- No severe combined heart, brain, lung, liver or kidney disease, judged by the investigator to tolerate the study regimen
- Able to understand and voluntarily sign a written informed consent form
Exclusion Criteria:
- BCR::ABL-positive MPAL patients
- Presence of active, uncontrolled infection
- Known uncontrolled active central nervous system leukemia (CNSL)
- Life-threatening extramedullary disease requiring urgent radiotherapy or surgical debulking
- Severe cardiac insufficiency with left ventricular ejection fraction (LVEF) <40%
- Previous receipt of systemic anti-leukemia therapy
- Pregnant or lactating female subjects
- Judged by the investigator to be ineligible for the study for other reasons
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Нерандомизированный
- Интервенционная модель: Параллельное назначение
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
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Экспериментальный: Cohort A: T/Myeloid MPAL
Sonrotoclax: 40mg qd (D1), 80mg qd (D2), 160mg qd (D3), 320mg qd (D4-D21), oral; Azacitidine: 75mg/m² qd (D1-D7), subcutaneous injection; 28-day cycle, ≥2 cycles. Patients who achieve CRc will undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) following 2 to 3 cycles of consolidation therapy. |
Sonrotoclax:40mg qd (D1), 80mg qd (D2), 160mg qd (D3), 320mg qd (D4-D21), oral;
Другие имена:
75mg/m² qd (D1-D7), subcutaneous injection; 28-day cycle, ≥2 cycles
Другие имена:
|
|
Экспериментальный: Cohort B: B/Myeloid MPAL
Sonrotoclax: 40mg qd (D1), 80mg qd (D2), 160mg qd (D3), 320mg qd (D4-D21), oral; Azacitidine: 75mg/m² qd (D1-D7), subcutaneous injection; Blinatumomab: 9μg/day (D8-D14), 28μg/day (D15-D21), continuous intravenous infusion; 28-day cycle, ≥2 cycles. Patients who achieve CRc will undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) following 2 to 3 cycles of consolidation therapy. |
Sonrotoclax:40mg qd (D1), 80mg qd (D2), 160mg qd (D3), 320mg qd (D4-D21), oral;
Другие имена:
75mg/m² qd (D1-D7), subcutaneous injection; 28-day cycle, ≥2 cycles
Другие имена:
9μg/day (D8-D14), 28μg/day (D15-D21), continuous intravenous infusion
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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Composite Complete Response (CRc) rate after 2 cycles of induction therapy
Временное ограничение: From randomization to 2 cycles of induction before consolidation therapy（100 days）
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CRc = CR + CRi; CR: bone marrow blasts <5%, no extramedullary disease, no peripheral blasts, ANC ≥1.0×10⁹/L,
PLT ≥100×10⁹/L; CRi: bone marrow blasts <5%, no extramedullary disease, no peripheral blasts, incomplete hematologic recovery (ANC <1.0×10⁹/L or PLT <100×10⁹/L)
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From randomization to 2 cycles of induction before consolidation therapy（100 days）
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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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MRD negativity rate
Временное ограничение: From randomization to 2 cycles of induction before consolidation therapy（100 days）
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Bone marrow MRD <0.01%
detected by MFC
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From randomization to 2 cycles of induction before consolidation therapy（100 days）
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NGS-MRD negativity rate
Временное ограничение: From randomization to 2 cycles of induction before consolidation therapy（100 days）, and test Every 3 months during follow-up
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NGS-MRD can not detected by IgH/TCR NGS (NGS-based MRD will be incorporated as an exploratory complementary assay in patients with trackable clonotypic rearrangements at diagnosis)
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From randomization to 2 cycles of induction before consolidation therapy（100 days）, and test Every 3 months during follow-up
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CR1 bridge-to-allo-HSCT rate
Временное ограничение: Up to 6 months after enrollment
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Proportion of subjects who achieve CR/CRi and successfully receive allo-HSCT within 2-3 cycles
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Up to 6 months after enrollment
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Overall Survival (OS)
Временное ограничение: From the time from randomization to time for up to 2 years
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Time from C1D1 to death from any cause; data censored at last follow-up for surviving subjects
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From the time from randomization to time for up to 2 years
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Event-Free Survival (EFS)
Временное ограничение: From the time from randomization to time for up to 2 years
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Time from C1D1 to first event (no CRc after 2 cycles, morphological/extramedullary relapse, disease progression, off-protocol anti-leukemia therapy, death from any cause); data censored at last follow-up for event-free subjects
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From the time from randomization to time for up to 2 years
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Relapse-Free Survival (RFS)
Временное ограничение: From the time from randomization to time for up to 2 years
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Time from first CR/CRi to relapse or death from any cause; relapse defined as bone marrow blasts ≥5%, extramedullary disease, peripheral blasts, or molecular MRD ≥10-⁴ in previously MRD-negative patients;data censored at last follow-up for relapse-free subjects
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From the time from randomization to time for up to 2 years
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100-day Non-Relapse Mortality (100-day NRM)
Временное ограничение: Up to 100 days after initial MPAL diagnosis
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Proportion of deaths from non-relapse causes within 100 days of diagnosis
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Up to 100 days after initial MPAL diagnosis
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Incidence of grade ≥3 adverse events (AEs)
Временное ограничение: From treatment initiation to the end of Induction
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Type, frequency and severity of grade ≥3 AEs graded by CTCAE v5.0
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From treatment initiation to the end of Induction
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Соавторы и исследователи
Следователи
- Главный следователь: Suning Chen, The First Affiliated Hospital of Soochow University Principal Investigator
Даты записи исследования
Изучение основных дат
Начало исследования (Оцененный)
Первичное завершение (Оцененный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Дополнительные соответствующие термины MeSH
Другие идентификационные номера исследования
- MPAL-1
Планирование данных отдельных участников (IPD)
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Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
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