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

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.

Conditions

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

Interventions

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)

Sponsors & Collaborators

• Bambino Gesù Hospital and Research Institute

  lead OTHER

Principal Investigators

• Franco Locatelli, Professor · IRCSS Ospedale Pediatrico Bambino Gesù

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

3 Months

Max Age

25 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-01-15

Primary Completion

2032-11-30

Completion

2032-12-01

Countries

• Austria
• Czechia
• Denmark
• Finland
• France
• Germany
• Italy
• Norway
• Poland

Study Locations