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

ConditionsAcute Lymphoblastic Leukemia (ALL)Stem Cell TransplantGraft -Versus-host-disease
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

This trial does not accept healthy volunteers

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

Design model

Parallel

Treatments tested in this trial

  • 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 intervention

    Ex vivo graft manipulation based on selective depletion of T-cell receptor αβ (TCR αβ+)/CD19+ lymphocytes from the graft (αβ T-cells depletion)

Treatment groups

1,000 Participants
are divided into 4 treatment groups
Group A: R1 substudyExperimental treatment 2 interventions
Group B: R2 substudyExperimental treatment 2 interventions
Group C: S1 substudyExperimental treatment 2 interventions
Group D: P1 substudyActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

Event Free Survival (EFS)

EFS is defined as the time from randomization (intention-to-treat analysis) or HSCT (per-protocol/as treated) to first failure event defined as follows: Failure events are: * Relapse * Graft failure * Death from any cause * Diagnosis of a second malignant neoplasm

Time frame
at year 4
2

Overall response rate (ORR) at day 28

Overall response rate (ORR) at day 28 after randomization, defined as the proportion of patients in each arm demonstrating a complete response (CR) or partial response (PR) without requirement for additional systemic therapies for earlier progression, mixed response or nonresponse.

Time frame
day 28
3

Event Free Survival (EFS)

EFS is defined as the time from HSCT to first failure event defined as follows: Failure events are: * Relapse * Graft failure * Death from any cause * Diagnosis of a second malignant neoplasm

Time frame
at year 4
4

Cumulative incidence of relapse (CIR) at 2 years after HSCT

CIR at 2 years after HSCT in blinatumomab-treated patents and historical controls. CIR is calculated from the time of study enrolment until the date of relapse (defined as either bone marrow aspirate or biopsy with ≥ 5% blasts or as appearance of leukemia cells in an extramedullary site) or last follow-up (death from any cause other than leukemia relapse and secondary malignancies will be considered a competing event)

Time frame
2 years after HSCT

Secondary outcomes

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Bambino Gesù Hospital and Research Institute

Lead sponsor

Source ClinicalTrials.gov

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