NCT07297914

Framework for Optimizing, Refining, and Unifying Management of HSCT in Pediatric ALL

• Status: Not Yet Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 1,000 (estimated)
• Sponsor: Bambino Gesù Hospital and Research Institute · Academic / Other
• Sex: All
• Age: 3 Months – 25 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

The key focus areas and objectives include: * Optimization of conditioning regimens * Advancements in GvHD prevention and treatment * Integration of novel immunotherapies * Improvement of long-term survivorship * Harmonization of supportive care and post-transplant monitoring * Expansion of donor availability The FORUM2 study comprises two randomized comparisons (R1 and R2 substudies), one stratified cohort (S1 substudy), and one pilot cohort (P1 substudy). The protocol is structured as a master protocol, with the R1 substudy serving as the central component because it represents the continuation of the FORUM1 study (which compared TBI-based and chemotherapy-based conditioning) and is expected to enroll the majority of patients. Patients ineligible for the R1 substudy-due to age (\<2 years), donor type, physician discretion, or personal preference-will still be included in the master protocol and monitored accordingly. Patients transplanted from a mismatched family donor will be stratified within the S1 substudy. Additionally, patients younger than 2 years of age with B-ALL are eligible for the P1 pilot substudy, which will investigate the use of post-HSCT blinatumomab to reduce relapse incidence in this high-risk population. Primary and secondary endpoints, general assessment timelines, and supportive care guidelines will remain consistent for both R1 substudy participants and patients included in the broader master protocol. Additional assessments, endpoints, and interventions specific to other study groups are outlined in their respective protocol sections (or appendices) and will be conducted exclusively for patients enrolled in those specific cohorts.

Conditions

• Acute Lymphoblastic Leukemia (ALL)
• Stem Cell Transplant
• Graft -Versus-host-disease

Interventions

Type	Name	Description
RADIATION	Total Body Irradiation 8 Gy	Total Body Irradiation 8 Gy administered in combination with VP16 as part of the conditioning regimen
COMBINATION_PRODUCT	Ruxolitinib	Ruxolitinib plus corticosteroids in treatment-naïve acute graft-versus-host disease
DRUG	Blinatumomab	Up to four cycles of blinatumomab as post-HSCT maintenance therapy
DRUG	Cyclophosphamide	In vivo T-cells depletion/modulation with post-transplant cyclophosphamide
RADIATION	Total Body Irradiation 12 Gy	Total Body Irradiation 12 Gy administered in combination with VP16 as part of the conditioning regimen
DRUG	Corticosteroids	Corticosteroids alone in treatment-naïve acute graft-versus-host disease
OTHER	αβ T-cells depletion	Ex vivo graft manipulation based on selective depletion of T-cell receptor αβ (TCR αβ+)/CD19+ lymphocytes from the graft (αβ T-cells depletion)

Timeline

• Start date: 2026-01-15
• Primary completion: 2032-11-30
• Completion: 2032-12-01
• First posted: 2025-12-22
• Last updated: 2025-12-22

Locations

9 sites across 9 countries: Austria, Czechia, Denmark, Finland, France, Germany, Italy, Norway, Poland