NCT07175415

HEM-iSMART E: Capivasertib + Venetoclax + Dexamethasone in Pediatric Patients With Relapsed or Refractory Hematological Malignancies

ITCC-104: HEM-iSMART International Proof of Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory HEMatological Malignancies in Children, Sub-Protocol E: Capivasertib + Venetoclax + Dexamethasone in Pediatric Patients With Relapsed or Refractory Hematological Malignancies

• Status: Not Yet Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Sponsor: Princess Maxima Center for Pediatric Oncology · Academic / Other
• Sex: All
• Age: 2 Years – 21 Years
• Healthy volunteers: Not accepted

Summary

HEM-iSMART is a master protocol which investigates multiple investigational medicinal products in children, adolescents and young adults (AYA) with relapsed/refractory (R/R) ALL and LBL. Sub-protocol E is a phase I/II trial evaluating the safety and efficacy of capivasertib + venetocolax in combination with dexamethasone in children and AYA with R/R ped ALL/LBL whose tumor present with alterations of the PAM pathway, or lacking any mutations.

Detailed description

HEM-iSMART is a master protocol with sub-protocols. The overarching objective is that introducing targeted therapy using a biomarker driven approach for treatment stratification may improve the outcome of children with R/R acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) It is characterized by a shared framework that allows for the investigation of multiple IMPs and generate pivotal safety and efficacy evidence within the sub-protocols to establish and define the benefits and risks of new treatments for children with R/R leukemia. Sub-protocol E within HEM-iSMART is a phase I/II, multicenter, international, open-label clinical trial designed to evaluate the safety, tolerability, pharmacokinetics (PK) and efficacy of capivasertib + venetoclax in combination with dexamethasone in children, adolescents and young adults with relapsed or refractory (R/R) hematological malignancies including ALL and LBL. Patients in must present alterations of the PAM pathway, or can be enrolled on a generic base lacking any mutations.

Conditions

• Acute Lymphoblastic Leukemia
• Lymphoblastic Lymphoma (Precursor B-Lymphoblastic Lymphoma/Leukaemia) Recurrent
• Lymphoblastic Lymphoma (Precursor B-Lymphoblastic Lymphoma/Leukaemia) Refractory
• Lymphoblastic Lymphoma (Precursor T-Lymphoblastic Lymphoma/Leukaemia) Recurrent
• Lymphoblastic Lymphoma (Precursor T-Lymphoblastic Lymphoma/Leukaemia) Refractory

Interventions

Type	Name	Description
DRUG	Capivasertib	Oral
DRUG	Venetoclax	Oral
DEVICE	Dexamethasone	oral/intravenous
DRUG	Intrathecal chemotherapy	IT: Methotrexate +/- prednisone/hydrocortisone/cytarabine according to the degree of central nervous involvement

Timeline

• Start date: 2026-10-01
• Primary completion: 2031-10-01
• Completion: 2032-10-01
• First posted: 2025-09-16
• Last updated: 2025-09-16