Framework for Optimizing, Refining, and Unifying Management of HSCT in Pediatric ALL
Trial statusNot yet recruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age3-25
SponsorBambino Gesù Hospital and Research Institute
About this trial
Current therapeutic strategies for high-risk or relapsed ALL patients often involve intensive treatments, including allogeneic hematopoietic stem cell transplantation (HSCT). HSCT remains a cornerstone of therapy, offering curative potential; however, it is associated with considerable risks, including non-relapse mortality (NRM), significant morbidity, and long-term complications that continue to be major concerns.
In response to these challenges, the FORUM consortium has made substantial progress in improving outcomes for children with ALL undergoing HSCT. The consortium focuses on reducing life-threatening and lifelong complications, ultimately aiming to enhance quality of life for these high-risk patients. Building on the robust evidence generated by FORUM1, the FORUM2 study has been designed to further optimize the role of HSCT in ALL across all age groups and donor settings within a harmonized and internationally coordinated framework.
The FORUM2 study introduces a master protocol structure that encompasses multiple hypothesis-driven substudies, each addressing a specific determinant of HSCT outcomes. This design enables simultaneous or sequential evaluation of novel strategies while ensuring uniform governance, endpoint definitions, and data-quality standards. The overarching objective is to refine the role of HSCT in ALL by reducing treatment-related toxicity while preserving the essential graft-versus-leukemia effect.
Eligibility criteria
Qualifiers
Male and female patients with allogenic transplant indication for ALL, as determined by national frontline protocols
Age ≥3 months to ≤25 years at the time of HSCT.
Patients must be in complete remission (with <5% blasts and absence of leukemia cells in extramedullary sites) prior to undergoing HSCT.
Selected donor must be either a matched donor (matched donor category includes 9/10 identical siblings and 10/10 or 9/10 HLA-matched unrelated donors) or a mismatched family donor (≤8/10 HLA match). Either bone marrow or peripheral blood stem cell grafts are permitted. Cord blood is permitted, as well, provided that the unit is at least 6/8 HLA matched and with a cryopreserved cellularity of at least 3x107 nucleated cells/Kg recipient body weight.
Disqualifiers
Patients < 3 months and > 25 years of age at the time of HSCT.
Patients not in complete morphological remission at the time of enrollment.
Patients with an initial diagnosis of Non-Hodgkin Lymphoma (NHL).
Patients with ALL as a secondary malignancy.
Trial design
Treatments tested in this trial
- Total Body Irradiation 8 Gy
- Ruxolitinib
- Blinatumomab
- Cyclophosphamide
- Total Body Irradiation 12 Gy
- Corticosteroids
- αβ T-cells depletion
Treatment groups
1,000 Participants
are divided into 4 treatment groupsSponsors and collaborators
Source ClinicalTrials.gov