Acute Lymphoblastic Leukemia
Conditions
Keywords
ALL, adult, Philadephia-negative, minimal residual disease, genetics, immunotherapy, transplantation
Brief summary
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.
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.
Interventions
DRUGPediatric-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.
PROCEDURETransplantation
allogeneic stem cell transplantation
Sponsors
PETHEMA Foundation
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival comparison versus previous trial | 5 years | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete remission (CR) rate | 4 or 8 weeks after treatment onset | Proportion of participants who achieve CR with or 2 induction therapy lines |
| MRD status after induction and consolidation | After induction (4-8 weeks) and consolidation (16-20 weeks) | Proportion of participants who achieve and maintain the negative MRD status (\<10-4) |
| MRD variation between induction and after cycle 1 blinatumomab | After induction (4-8 weeks) and after cycle 1 blinatumomab (8-12 weeks) | 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) |
| Frequency of allogeneic stem cell transplantation (alloSCT) dut to high-risk genetics | 5 years | Proportion of participants that are allocated to alloSCT exclusively due to the presence to high-risk genetic alterations defined in the trial |
| Effect of blinatumomab within each B-cell precursor ALL genetic subtype | 5 years | 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) |
Countries
Spain
Contacts
CONTACTAnna Torrent, Dr
CONTACTJosep Maria Ribera
STUDY_CHAIRAnna Torrent, Dr
Germans Trias i Pujol Hospital
STUDY_CHAIRPere Barba, Dr
Hospital Vall d'Hebrón
STUDY_CHAIRJosep Maria Ribera, Prof
Germans Trias i Pujol Hospital
Outcome results
None listed