Treatment for Ph-negative ALL for Adults up to 65 Years

Официальное название

Protocol for the Treatment of BCR::ABL1-negative Acute Lymphoblastic Leukemia in Adults up to 65 Years

Обзор

The goal of this trial is to provide a protocol for treatment for adults with Ph-negative acute lymphoblastic leukemia (ALL) and to learn if this provides higher probability of survival than the previous one. The main question is to know if the incorporation of blinatumomab for B-cell precursor ALL, substituting some chemotherapy blocks, offers better probability of survival than the previous trial, which did not use immunotherapy. In addition, T-cell precursor ALL participants will receive different treatment approaches depending on the stage of maturation of the tumor.

Подробное описание

Participants will be uniformly treated with four drug-induction: vincristine (VCR), prednisone (PDN), pegylated asparaginase (PegASP), daunorubicin (DNR).

Resistant participants will receive a second induction with inotuzumab for B-cell precursor ALL or with FLAG-Ida (fludarabine, cytarabine, idarubicin and granulocyte colony stimulating factor) for T-cell precursor ALL.

B-cell precursor ALL participants with adequate MRD clearance after cycle 1 of blinatumomab will receive 3 blocks of early consolidation. If adequate MRD clearance and good genetic background, the patients will proceed to delayed intensification, reinduction and maintenance. The remaining patients will receive early or delayed alloHSCT.

T-cell precursor ALL participants with adequate MRD clearance after the first cycle of consolidation will receive 2 blocks of early consolidation and reinduction. If adequate MRD clearance and good genetic background, the patients will proceed to delayed intensification and maintenance. The remaining patients will receive early or delayed alloHSCT.

Вмешательства

• Препарат Pediatric-type of chemotherapy (+blinatumomab for B-cell precursor ALL)
  Pediatric type chemotherapy (induction, early and delayed consolidation, reinduction, maintenance). Induction (VCR,PDN,PegASP,DNR). Early and delayed consolidation (high-dose Methotrexate, high-dose Cytarabine, PegASP). Reinduction (VCR, PDN, PegASP, DNR). Maintenance (Methotrexate, Mercaptopurine). Blinatumomab cycles in consolidation therapy for participants with B-cell precursor ALL.
• Процедура Transplantation
  allogeneic stem cell transplantation

Первичные конечные точки

• Overall survival comparison versus previous trial [Срок оценки: 5 years]

Вторичные конечные точки (5)

• Complete remission (CR) rate [Срок оценки: 4 or 8 weeks after treatment onset]
• MRD status after induction and consolidation [Срок оценки: After induction (4-8 weeks) and consolidation (16-20 weeks)]
• MRD variation between induction and after cycle 1 blinatumomab [Срок оценки: After induction (4-8 weeks) and after cycle 1 blinatumomab (8-12 weeks)]
• Frequency of allogeneic stem cell transplantation (alloSCT) dut to high-risk genetics [Срок оценки: 5 years]
• Effect of blinatumomab within each B-cell precursor ALL genetic subtype [Срок оценки: 5 years]

Критерии участия

Критерии включения

• De novo ALL.
• Age 18-65 years.
• No prior treatment, except:

Urgent leukapheresis, Urgent treatment of hyperleukocytosis with hydroxyurea, Urgent cranial irradiation (one dose) for CNS leukostasis, Urgent mediastinal irradiation for superior vena cava syndrome.

• Adequate general condition (ECOG score 0-2), or >2 if due to ALL.
• Negative pregnancy test for women of childbearing age.

Критерии исключения

• Age > 65 years.
• ALL type L3 or with mature B phenotype (sIg+) or with the cytogenetic alterations characteristic of mature B-cell ALL (t(8;14), t(2;8), t(8;22)).
• Ph-positive B-cell ALL (BCR::ABL1).
• Lymphoid blast crisis of chronic myeloid leukemia.
• Patients with a history of coronary artery disease, valvular heart disease, or hypertensive heart disease, which contraindicates the use of anthracyclines.
• Patients with active chronic liver disease.
• Patients with severe chronic respiratory failure.
• Renal insufficiency not due to ALL.
• Severe neurological disorders, not due to ALL, that contraindicate the use of these treatments (especially blinatumomab).
• History of clinically significant pancreatitis, at the investigator's discretion (taking into account the date of the pancreatitis, its previous severity, and sequelae).
• Pregnancy or breastfeeding.
• Psychiatric or mental illness that prevents providing informed consent for sample submission or adequately participating in the study.
• Impaired general health (ECOG scores 3 and 4) not attributable to ALL.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Испания · 95 центров

• Hospital de A Coruña — A Coruña
• Hospital Universitario de Araba — Alava
• Hospital General Universitario de Albacete — Albacete
• Hospital General Universitario Dr. Balmis — Alicante
• Hospital Universitario Torrecárdenas — Almería
• Hospital General de Lanzarote — Arrecife
• Hospital Nuestra Señora de Sonsoles / Complejo Asistencial de Ávila — Ávila
• Hospital Universitario de Badajoz — Badajoz
• … и ещё 87 центров

Идентификаторы

NCT: NCT07443592 · PETHEMA LAL-2025

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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