Идёт набор NCT07059156

Multicenter Study of Combined Chemotherapy and Transplantation for Adult ALL

Фаза II / Фаза III С лечением Acute Lymphoblastic Leukemia, Adult

Ориентир для пациента и семьи

Простыми словами

Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.

Что изучают: В протоколе указаны: Induction Therapy Regimen, Pre-Treatment Regimen, Post-CR Treatment, Post-CR Consolidation Regimens.
Кому может быть актуально: Состояния в реестре: Acute Lymphoblastic Leukemia, Adult. Базовые параметры: 18 лет — 60 лет · Все.
Что важно проверить: Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
Где проводится: Китай
Следующий шаг: Сохраните исследование, покажите его лечащему врачу и уточните актуальный статус у исследовательского центра. Расходы, документы и поездка →

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Официальное название

Multicenter Study on Integrated Treatment Regimen of Induction-Consolidation Chemotherapy and Transplantation for Adult Acute Lymphoblastic Leukemia

Обзор

This study aims to evaluate an integrated treatment protocol for adults with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL), combining induction chemotherapy, consolidation therapy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) to improve treatment efficacy and survival rates. The single-arm, open-label, multicenter study will enroll 50 newly diagnosed patients aged 18-60 years. The induction phase employs the VICP+VEN regimen (vindesine, idarubicin, cyclophosphamide, prednisone combined with venetoclax), followed by consolidation therapy with either Hyper-CVAD or CAM protocols, with eligible patients proceeding to allo-HSCT. Primary endpoints include disease-free survival (DFS) and complete remission (CR) rates, while secondary endpoints encompass relapse rate, overall survival (OS), and safety. Patients will be followed for 2 years with regular monitoring of minimal residual disease (MRD) and adverse events. The protocol is designed to reduce relapse risk through intensive therapy and transplantation, offering a potential cure for high-risk patients.The goal is to complete the entire treatment within 4 months after diagnosis.

Подробное описание

1\. Intervention Measures 1.1 Induction Therapy Regimen

VICP+VEN regimen:

* Vindesine: 3 mg/m²/day (max 4 mg), administered on days 1, 8, 15, 22. * Idarubicin (IDA): 8 mg/m², days 1, 8, 15, 22. * Cyclophosphamide (CTX): 500 mg/m², days 7, 21. * Prednisone: 1 mg/kg/day, days 1-14; 0.5 mg/kg/day, days 15-28 * Venetoclax (VEN) 8-day ramp-up: Day 1: 100 mg, Day 2: 200 mg, Days 3-8: 400 mg/day 1.2 Pre-Treatment Regimen

Indications for pre-treatment:

* WBC ≥30×10⁹/L, or significant hepatosplenomegaly/lymphadenopathy. * Laboratory signs of tumor lysis syndrome (e.g., electrolyte abnormalities).

Pre-treatment protocol:

* Glucocorticoids (e.g., prednisone or dexamethasone): Prednisone 1 mg/kg/day (PO/IV) for 3-5 days. * Optional addition of CTX: 200 mg/m²/day IV for 3-5 days. 1.3 Post-CR Treatment

Principles:

1. MRD-positive or rising: Administer blinatumomab (CD19/CD3 bispecific antibody) for residual disease clearance, followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). 2. MRD-negative/unknown: Continue multi-agent chemotherapy ± blinatumomab consolidation. Allo-HSCT for patients with high-risk clinical/genetic features.

1.4 Post-CR Consolidation Regimens

① Hyper-CVAD-B (Methotrexate/Cytarabine-based): * Methotrexate (MTX): 1 g/m² IV over 24h (Day 1) with urine alkalinization (pH \>7.0) and leucovorin rescue. * Cytarabine (Ara-C): 1 g/m² IV q12h (Days 2-3; total 4 doses). * Dexamethasone: 40 mg/day (PO/IV, Days 1-4). * Cycle interval: 21-28 days (alternating with other regimens).

* CAM Regimen: * CTX: 750 mg/m² IV (split over 2 days). * Ara-C: 75 mg/m²/dose (8 days; 1-2 doses/day IV; if once daily, administer 5 days/week × 2 weeks). * 6-MP: 50-75 mg/m²/day fasting (7-14 days PO). 1.5 Transplant-Eligible Subsequent Therapy * Allo-HSCT for eligible patients after induction. * Conditioning regimen: TBI-VP16-CY. * Donor priority: HLA-matched sibling donor (MSD), Matched unrelated donor (MUD), Haploidentical donor (Haplo). (Consider age/donor health status).

1.6 Allo-HSCT Protocol 1.6.1 Conditioning Regimen (TBI-VP16-Cy/ATG):

• TBI: 5 Gy (Days -7 to -6). * VP16: 10 mg/kg/day (Days -5 to -4). * CTX: 30 mg/kg/day (Days -3 to -2). * ATG: 7.5 mg/kg/day (Days -5 to -2). 1.6.2 GVHD Prophylaxis: * Basiliximab (anti-CD25 mAb): 50 mg (Days +1, +4). * Standard regimen: Cyclosporine (CsA): IV: 2 mg/kg/day (start Day -9; target level 150-250 μg/L). PO: 3-5 mg/kg/day BID (switch delayed until Day +10 if no aGVHD); Mycophenolate mofetil (MMF) + short-course methotrexate.

1.7 Non-Transplant Maintenance Therapy

Options: * Hyper-CVAD-B (Methotrexate/Cytarabine-based):

• Methotrexate (MTX): 1 g/m² IV over 24h (Day 1) with urine alkalinization (pH \>7.0) and leucovorin rescue.

• Cytarabine (Ara-C): 1 g/m² IV q12h (Days 2-3; total 4 doses).

• Dexamethasone: 40 mg/day (PO/IV, Days 1-4). * Cycle interval: 21-28 days (alternating with other regimens).

* Maintenance (6-MP/MTX alternating with V-Dex): 6-MP: 75 mg/m²/day at bedtime (Days 1-21); MTX: 20 mg/m² IM weekly × 3 weeks.\*Adjust doses to maintain WBC \~3×10⁹/L, ANC 1.0-1.5×10⁹/L.\*

Вмешательства

Препарат Induction Therapy Regimen
VICP+VEN regimen: * Vindesine: 3 mg/m²/day (max 4 mg), administered on days 1, 8, 15, 22. * Idarubicin (IDA): 8 mg/m², days 1, 8, 15, 22. * Cyclophosphamide (CTX): 500 mg/m², days 7, 21. * Prednisone: 1 mg/kg/day, days 1-14; 0.5 mg/kg/day, days 15-28 * Venetoclax (VEN) 8-day ramp-up: Day 1: 100 mg, Day 2: 200 mg, Days 3-8: 400 mg/day
Препарат Pre-Treatment Regimen
Indications for pre-treatment: * WBC ≥30×10⁹/L, or significant hepatosplenomegaly/lymphadenopathy. * Laboratory signs of tumor lysis syndrome (e.g., electrolyte abnormalities). Pre-treatment protocol: * Glucocorticoids (e.g., prednisone or dexamethasone): Prednisone 1 mg/kg/day (PO/IV) for 3-5 days. * Optional addition of CTX: 200 mg/m²/day IV for 3-5 days.
Другое Post-CR Treatment
Principles: 1. MRD-positive or rising: Administer blinatumomab (CD19/CD3 bispecific antibody) for residual disease clearance, followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). 2. MRD-negative/unknown: Continue multi-agent chemotherapy ± blinatumomab consolidation. Allo-HSCT for patients with high-risk clinical/genetic features.
Препарат Post-CR Consolidation Regimens
① Hyper-CVAD-B (Methotrexate/Cytarabine-based): * Methotrexate (MTX): 1 g/m² IV over 24h (Day 1) with urine alkalinization (pH \>7.0) and leucovorin rescue. * Cytarabine (Ara-C): 1 g/m² IV q12h (Days 2-3; total 4 doses). * Dexamethasone: 40 mg/day (PO/IV, Days 1-4). * Cycle interval: 21-28 days (alternating with other regimens). ② CAM Regimen: * CTX: 750 mg/m² IV (split over 2 days). * Ara-C: 75 mg/m²/dose (8 days; 1-2 doses/day IV; if once daily, administer 5 days/week × 2 weeks). * 6-MP: 5
Другое Transplant-Eligible Subsequent Therapy
* Allo-HSCT for eligible patients after induction. * Conditioning regimen: TBI-VP16-CY. * Donor priority: HLA-matched sibling donor (MSD), Matched unrelated donor (MUD), Haploidentical donor (Haplo).(Consider age/donor health status).
Другое Allo-HSCT Protocol
1.6.1 Conditioning Regimen (TBI-VP16-Cy/ATG): * TBI: 5 Gy (Days -7 to -6). * VP16: 10 mg/kg/day (Days -5 to -4). * CTX: 30 mg/kg/day (Days -3 to -2). * ATG: 7.5 mg/kg/day (Days -5 to -2). 1.6.2 GVHD Prophylaxis: * Basiliximab (anti-CD25 mAb): 50 mg (Days +1, +4). * Standard regimen: Cyclosporine (CsA): IV: 2 mg/kg/day (start Day -9; target level 150-250 μg/L). PO: 3-5 mg/kg/day BID (switch delayed until Day +10 if no aGVHD); Mycophenolate mofetil (MMF) + short-course methotrexate.
Другое Non-Transplant Maintenance Therapy Options
① Hyper-CVAD-B (Methotrexate/Cytarabine-based): * Methotrexate (MTX): 1 g/m² IV over 24h (Day 1) with urine alkalinization (pH \>7.0) and leucovorin rescue. * Cytarabine (Ara-C): 1 g/m² IV q12h (Days 2-3; total 4 doses). * Dexamethasone: 40 mg/day (PO/IV, Days 1-4). * Cycle interval: 21-28 days (alternating with other regimens). ② CAM Regimen: * CTX: 750 mg/m² IV (split over 2 days). * Ara-C: 75 mg/m²/dose (8 days; 1-2 doses/day IV; if once daily, administer 5 days/week × 2 weeks). * 6-MP: 5

Первичные конечные точки

Disease-free survival (DFS) [Срок оценки: 24 months]
Complete remission (CR) rate [Срок оценки: 24 months]
Partial remission (PR) rate [Срок оценки: 24 months]
Non-remission (NR) rate [Срок оценки: 24 months]
CR with incomplete hematologic recovery (CRi) [Срок оценки: 24 months]

Вторичные конечные точки (6)

Relapse rate [Срок оценки: 24 months]
Treatment-related mortality（TRM） [Срок оценки: 24 months]
Overall Survival（OS） [Срок оценки: 24 months]
Event-Free Survival（EFS） [Срок оценки: 24 months]
Adverse Event [Срок оценки: 24 months]
Mortality [Срок оценки: 24 months]

Критерии участия

Критерии включения

Age: 18 to 60 years；
Diagnosis must comply with the Chinese Guidelines for Diagnosis and Treatment of Adult Acute Lymphoblastic Leukemia (2024 Edition), requiring MICM (Morphology, Immunology, Cytogenetics, and Molecular genetics) integration and WHO 2022 (5th edition) classification standards. The minimal diagnostic workup must include morphological assessment and immunophenotyping to differentiate ALL from acute myeloid leukemia (AML). All patients shall undergo bone marrow aspiration plus biopsy at initial diagnosis. A definitive ALL diagnosis requires ≥20% blasts/immature lymphocytes in bone marrow (Note: Patients with <20% blasts due to fever or glucocorticoid pretreatment require comprehensive evaluation incorporating medical history and ancillary tests for differential diagnosis)；
ECOG Performance Status: 0-2