Treatment for Ph-negative ALL for Adults up to 65 Years (LAL-2025)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Pediatric-type of chemotherapy (+blinatumomab for B-cell precursor ALL); Procedure: Transplantation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 330
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anna Torrent, Dr; Phone Number: +34934978987; Email: atorrent@iconcologia.net
• Study Contact Backup: Name: Josep Maria Ribera; Phone Number: +34934978987; Email: jribera@iconcologia.net

Study Locations

• Spain
  • A Coruña, Spain
    • Hospital de A Coruña
    • Principal Investigator: Victor Noriega, Dr
  • Alava, Spain
    • Hospital Universitario de Araba
    • Principal Investigator: Pilar Romero, Dr
  • Albacete, Spain
    • Hospital General Universitario de Albacete
    • Principal Investigator: Jesús Lorenzo Algarra, Dr
  • Alicante, Spain
    • Hospital General Universitario Dr. Balmis
    • Principal Investigator: Carmen Botella, Dr
  • Almería, Spain
    • Hospital Universitario Torrecárdenas
    • Principal Investigator: María José García, Dr
  • Arrecife, Spain
    • Hospital General de Lanzarote
    • Principal Investigator: Azueg Hong, Dr
  • Badajoz, Spain
    • Hospital Universitario de Badajoz
    • Principal Investigator: María Soledad Casado, Dr
  • Badalona, Spain
    • ICO-HOSPITAL GERMANS TRIAS I PUJOL
    • Principal Investigator: Anna Torrent, Dr
  • Barcelona, Spain
    • Hospital Clinic De Barcelona
    • Principal Investigator: Núria Martínez, Dr
  • Barcelona, Spain
    • Hospital del Mar
    • Principal Investigator: Lucía Gómez, Dr
  • Barcelona, Spain
    • Hospital de Sant Pau
    • Principal Investigator: Irene García, Dr
  • Barcelona, Spain
    • Hospital Vall d'Hebron
    • Principal Investigator: Pere Barba, Dr
  • Barcelona, Spain
    • Hospital QuirónSalud
    • Principal Investigator: Yva Rodríguez, Dr
  • Bilbao, Spain
    • Basurtuko Ospitalea
    • Principal Investigator: Cristina Barrenetxea, Dr
  • Burgos, Spain
    • Hospital Universitario de Burgos
    • Principal Investigator: Jorge Labrador, Dr
  • Cadiz, Spain
    • Hospital Puerta del Mar
    • Principal Investigator: José Ángel Raposo, Dr
  • Cartagena, Spain
    • Hospital Universitario Santa Lucía
    • Principal Investigator: Antonio Martínez, Dr
  • Castelló, Spain
    • Hospital General de Castellón
    • Principal Investigator: Raimundo García, Dr
  • Ciudad Real, Spain
    • Hospital General de Ciudad Real
    • Principal Investigator: Raúl Vanegas, Dr
  • Cruces, Spain
    • Hospital Universitario de Cruces
    • Principal Investigator: Javier Arzuaga, Dr
  • Cuenca, Spain
    • Hospital Virgen de la Luz
    • Principal Investigator: María José Busto, Dr
  • Cáceres, Spain
    • Hospital San Pedro Alcántara
    • Principal Investigator: Juan Bergua, Dr
  • Córdoba, Spain
    • Hospital Universitario Reina Sofia
    • Principal Investigator: Josefina Serrano, Dr
  • Donostia / San Sebastian, Spain
    • Hospital Universitario DE Donostia
    • Principal Investigator: Teresa Artola, Dr
  • Fuenlabrada, Spain
    • Hospital De Fuenlabrada
    • Principal Investigator: Pilar Bravo, Dr
  • Galdakao, Spain
    • Hospital Universitario de Galdakao
    • Principal Investigator: Matxalen Olivares, Dr
  • Getafe, Spain
    • Hospital de Getafe
    • Principal Investigator: Cristian Escolano, Dr
  • Girona, Spain
    • ICO-Hospital Josep Trueta
    • Principal Investigator: Marta Sitges, Dr
  • Huelva, Spain
    • Area Hospitalaria Juan Ramón Jimenez
    • Principal Investigator: María Solé, Dr
  • Jaén, Spain
    • Consorcio Hospitalario de Jaén
    • Principal Investigator: Juan Antonio López, Dr
  • Jerez de la Frontera, Spain
    • Hospital Jerez de la Frontera
    • Principal Investigator: Lourdes Hermosín, Dr
  • L'Hospitalet de Llobregat, Spain
    • ICO-Hospital Duran i Reynals
    • Principal Investigator: Clara Maluquer, Dr
  • Las Palmas de Gran Canaria, Spain
    • C. H. U. de Gran Canaria Dr. Negrín
    • Principal Investigator: Carlos Rodríguez, Dr
  • Las Palmas de Gran Canaria, Spain
    • Complejo Hospitalario Universitario Insular Materno Infantil de Canarias
    • Principal Investigator: Rosa Fernández, Dr
  • Leganés, Spain
    • Hospital Severo Ochoa
    • Principal Investigator: Lorena Abalo, Dr
  • León, Spain
    • Hospital Universitario de Leon
    • Principal Investigator: Nora Suárez, Dr
  • Lleida, Spain
    • Hospital Arnau de Vilanova
    • Principal Investigator: Antoni Garcia, Dr
  • Logroño, Spain
    • Hospital San Pedro
    • Principal Investigator: Andrea Campeny, Dr
  • Lugo, Spain
    • Hospital Universitario Lucus Augusti
    • Principal Investigator: Aitor Abuín, Dr
  • Madrid, Spain
    • Hospital Ramon y Cajal
    • Principal Investigator: Pilar Herrera, Dr
  • Madrid, Spain
    • Hospital Doce de Octubre
    • Principal Investigator: Pilar Martínez, Dr
  • Madrid, Spain
    • Hospital Clinico San Carlos
    • Principal Investigator: Marta Mateo, Dr
  • Madrid, Spain
    • Hospital Universitario La Paz
    • Principal Investigator: Irene Sánchez, Dr
  • Madrid, Spain
    • Hospital La Princesa
    • Principal Investigator: Javier Ortín, dr
  • Madrid, Spain
    • Hospital Infanta Leonor
    • Principal Investigator: María Ángeles Foncillas, Dr
  • Madrid, Spain
    • Hospital Universitario Fundacion Jimenez Diaz
    • Principal Investigator: Laura Solán, Dr
  • Madrid, Spain
    • Md Anderson Cancer Center
    • Principal Investigator: Alejandro Bobes, Dr
  • Madrid, Spain
    • Hospital Universitario Infanta Sofía
    • Principal Investigator: Alícia Roldán, Dr
  • Madrid, Spain
    • Hospital Príncipe de Asturias
    • Principal Investigator: Paula Gili, Dr
  • Madrid, Spain
    • Hospital Sanchinarro
    • Principal Investigator: Laura Llorente, Dr
  • Madrid, Spain
    • Hospital la Zarzuela
    • Principal Investigator: Daniel García, Dr
  • Madrid, Spain
    • Hospital Universitario Quirónsalud
    • Principal Investigator: Virginia Pradillo, Dr
  • Madrid, Spain
    • C. H. Gregorio Marañón
    • Principal Investigator: Ignacio Alberto Gómez, Dr
  • Madrid, Spain
    • Hospital Ruber Juan Bravo
    • Principal Investigator: Aranzazu Alonso, Dr
  • Madrid, Spain
    • Clinica Universidad Navarra
    • Principal Investigator: Carlos Grande, Dr
  • Madrid, Spain
    • Hospital Universitario HLA Moncloa
    • Principal Investigator: Concha Alaez, Dr
  • Majadahonda, Spain
    • Hospital Puerta de Hierro
    • Principal Investigator: Ana Bocanegra, Dr
  • Murcia, Spain
    • Hospital Morales Meseguer
    • Principal Investigator: María Luz Amigo, Dr
  • Murcia, Spain
    • Hospital Virgen de la Arrixaca
    • Principal Investigator: Joaquín Gómez, Dr
  • Málaga, Spain
    • . Hospital Clínico Universitario Virgen de la Victoria
    • Principal Investigator: María Paz Queipo, Dr
  • Málaga, Spain
    • Hospital QuirónSalud
    • Principal Investigator: Rahinatu Awol, Dr
  • Málaga, Spain
    • Hospital Regional Universitario de Málaga (Carlos Haya)
    • Principal Investigator: Daniel Barrios, Dr
  • Ourense, Spain
    • Complejo Hospitalario Universitario de Ourense
    • Principal Investigator: José Ángel Méndez, Dr
  • Oviedo, Spain
    • Hospital Central de Asturias
    • Principal Investigator: Teresa Bernal, Dr
  • Palencia, Spain
    • Complejo Asistencial de Palencia
    • Principal Investigator: Jackeline Solano, Dr
  • Palma de Mallorca, Spain
    • Hospital Son Espases
    • Principal Investigator: Andrés Novo, Dr
  • Palma de Mallorca, Spain
    • Hospital Universitari Son Llàtzer
    • Principal Investigator: Antonia Cladera, Dr
  • Pamplona, Spain
    • Hospital Universitario de Navarra
    • Principal Investigator: Maria Carmen Mateos, Dr
  • Pamplona, Spain
    • Clinica Universidad Navarra
    • Principal Investigator: José Rifón, Dr
  • Pontevedra, Spain
    • Complejo Hospitalario Pontevedra (CHUP)-Montecelo
    • Principal Investigator: María Lourdes Amador, Dr
  • Salamanca, Spain
    • C. Asistencial U. de Salamanca
    • Principal Investigator: Mónica Cabrero, Dr
  • Santa Cruz de Tenerife, Spain
    • Hospital Universitario de Canarias
    • Principal Investigator: Bernardo Javier González, Dr
  • Santa Cruz de Tenerife, Spain
    • Hospital Nuestra Señora Candelaria
    • Principal Investigator: María Teresa Busnego, Dr
  • Santander, Spain
    • Hospital Universitario Marques de Valdecilla
    • Principal Investigator: Arancha Bermúdez, Dr
  • Santiago de Compostela, Spain
    • C H Santiago de Compostela
    • Principal Investigator: Natalia Alonso, Dr
  • Segovia, Spain
    • Hospital General de Segovia
    • Principal Investigator: Ana Torres, Dr
  • Seville, Spain
    • Hospital Virgen del Rocío
    • Principal Investigator: José González, Dr
  • Seville, Spain
    • Consoorcio Hospitalario Virgen de Valme
    • Principal Investigator: Encarnación Gil, Dr
  • Seville, Spain
    • Hospital Virgen De La Macarena
    • Principal Investigator: Rafael Flores, Dr
  • Tarragona, Spain
    • ICO-Hospital Joan XXIII
    • Principal Investigator: Ana Vicent, Dr
  • Terrassa, Spain
    • Hospital Universitari Mutua Terrassa
    • Principal Investigator: Ferran Vall-llovera, Dr
  • Toledo, Spain
    • Hospital Universitario de Toledo
    • Principal Investigator: Laura Parrilla, Dr
  • Torrejón de Ardoz, Spain
    • Hospital Universitario de Torrejon
    • Principal Investigator: Mirian Santero, Dr
  • Valencia, Spain
    • Hospital Arnau de Vilanova
    • Principal Investigator: Carmen Benet, Dr
  • Valencia, Spain
    • Hospital Clinico de Valencia
    • Principal Investigator: Mar Tormo, Dr
  • Valencia, Spain
    • Hospital General de Valencia
    • Principal Investigator: Armando Mena-Duran, Dr
  • Valencia, Spain
    • Hospital Universitari i Politecnic La Fe
    • Principal Investigator: Pau Montesinos, Dr
  • Valencia, Spain
    • Hospital Doctor Peset
    • Principal Investigator: Miriam Panero, Dr
  • Valladolid, Spain
    • Hospital Rio Hortega
    • Principal Investigator: Alberto Cantalapiedra, Dr
  • Valladolid, Spain
    • Hospital Clinico Universitario de Valladolid
    • Principal Investigator: Lara Gómez, Dr
  • Vigo, Spain
    • Hospital Alvaro Cunqueiro
    • Principal Investigator: Sandra Suárez, Dr
  • Zamora, Spain
    • Complejo Asistencial de Zamora
    • Principal Investigator: Carmen Montes, Dr
  • Zaragoza, Spain
    • Hospital Lozano Blesa
    • Principal Investigator: Mayte Olave, Dr
  • Zaragoza, Spain
    • Hospital Miguel Servet
    • Principal Investigator: Beatriz de Rueda, Dr
  • Ávila, Spain
    • Hospital Nuestra Señora de Sonsoles / Complejo Asistencial de Ávila
    • Principal Investigator: María Paz Martínez, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Chemotherapy (+ blinatumomab for B-cell precursor ALL); Pediatric-inspired chemotherapy	Drug: 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.
Other: Transplantation; allogeneic stem cell transplantation	Procedure: Transplantation; allogeneic stem cell transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival comparison versus previous trial	Comparison of time from diagnosis to death or last follow-up between the present LAL-2025 trial and the previous LAL19 trial for adult Ph-negative	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission (CR) rate	Proportion of participants who achieve CR with or 2 induction therapy lines	4 or 8 weeks after treatment onset
MRD status after induction and consolidation	Proportion of participants who achieve and maintain the negative MRD status (<10-4)	After induction (4-8 weeks) and consolidation (16-20 weeks)
MRD variation between induction and after cycle 1 blinatumomab	Proportion of B-cell precursor ALL participants who achieve and maintain the negative MRD status (<10-4) at week 4 or 8 (end of induction 1 or 2) and after week 8 or 12 (after blinatumomab cycle1)	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	Proportion of participants that are allocated to alloSCT exclusively due to the presence to high-risk genetic alterations defined in the trial	5 years
Effect of blinatumomab within each B-cell precursor ALL genetic subtype	Proportion of paarticipants with negative MRD status within each B-cell precursor ALL genetic subtype according to the World Health Organization (WHO) and the International Consensus Classification of Acute Leukemia (ICC)	5 years

Collaborators and Investigators

• Sponsor: PETHEMA Foundation
• Investigators: Study Chair: Anna Torrent, Dr, Germans Trias i Pujol Hospital; Study Chair: Pere Barba, Dr, Hospital Vall d'Hebron; Study Chair: Josep Maria Ribera, Prof, Germans Trias i Pujol Hospital

Publications and helpful links

Helpful Links

• Webpage of the sponsor of the study

Study record dates

Study Major Dates

• Study Start (Estimated): March 6, 2026
• Primary Completion (Estimated): March 6, 2031
• Study Completion (Estimated): June 1, 2033

Study Registration Dates

• First Submitted: February 25, 2026
• First Submitted That Met QC Criteria: February 25, 2026
• First Posted (Actual): March 2, 2026

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 25, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: genetics; adult; immunotherapy; ALL; transplantation; minimal residual disease; Philadephia-negative
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Neoplastic Processes; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Neoplasm, Residual; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Surgical Procedures, Operative; blinatumomab; Transplantation
• Other Study ID Numbers: PETHEMA LAL-2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes