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

Sponsor
Bambino Gesù Hospital and Research Institute
Study ID
NCT07297914
Phase
PHASE2/PHASE3
Status
Not Yet Recruiting

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Conditions

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

Eligibility Criteria

Sex
ALL
Age
3 Months - 25 Years
Healthy Volunteers
Not accepted

Interventions

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

Study Details

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.

Key Dates

Start date
Jan 15, 2026
Status verified
Dec 2025
Primary completion
Nov 30, 2032
Completion
Dec 1, 2032

Study Design

Enrollment
1,000 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: R1 substudy
    A phase III, randomized, multi-center study comparing TBI 8 Gy versus TBI 12 Gy in children and young adults with ALL for conditioning of allogeneic HSCT
  • Experimental: R2 substudy
    A phase III, randomized, open-label multi-center study comparing ruxolitinib plus corticosteroids versus corticosteroids alone in children with ALL and treatment-naïve grade II-IV aGvHD following allogeneic HSCT
  • Experimental: S1 substudy
    A prospective stratified cohort study comparing between in vivo PT-Cy and ex vivo αβ T-cell depletion in mismatched donor transplantation for pediatric and young adult ALL.
  • Active Comparator: P1 substudy
    A phase II, open-label, multi-center study of blinatumomab following allogeneic HSCT for B-lineage ALL in children younger than 2 years not receiving TBI as part of the conditioning regimen

Primary Outcome Measure

Event Free Survival (EFS) [ Time Frame: at year 4 ]

Central Contacts

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