NCT05658640

HEM iSMART-D: Trametinib + Dexamethasone + Chemotherapy in Children With Relapsed or Refractory Hematological Malignancies

International Proof of Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory HEMatological Malignancies in Children, Subprotocol D: Trametinib + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric Patients With Relapsed or Refractory Hematological Malignancies

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 26 (estimated)
• Sponsor: Princess Maxima Center for Pediatric Oncology · Academic / Other
• Sex: All
• Age: 1 Year – 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 D is a phase I/II trial evaluating the safety and efficacy of trametinib in combination with dexamethasone, cyclophosphamide and cytarabine in children and AYA with R/R ped ALL/LBL whose tumor present with alterations in the RAS-RAF-MAPK pathway.

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 D 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 trametinib in combination with dexamethasone, cyclophosphamide and cytarabine in children, adolescents and young with R/R ALL and LBL. Patients with actionable alterations in the RAS-RAF-MAPK pathway will be eligible for sub-protocol D including but not limited to KRAS, NRAS, HRAS, FLT3, PTPN11, MAP2K1, MP2K1 hotspot mutations, cCBL; NF1 del.

Conditions

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

Interventions

Type	Name	Description
DRUG	Trametinib	Oral
DRUG	Dexamethasone	Oral/ Intravenous
DRUG	Cyclophosphamide	Intravenous
DRUG	Cytarabine	Intravenous
DRUG	Intrathecal chemotherapy	IT: Methotrexate +/- prednisone/hydrocortisone/cytarabine according to the degree of central nervous involvement

Timeline

• Start date: 2023-11-14
• Primary completion: 2029-04-01
• Completion: 2029-04-01
• First posted: 2022-12-21
• Last updated: 2025-09-16

Locations

36 sites across 15 countries: Austria, Belgium, Denmark, Finland, France, Germany, Ireland, Israel, Italy, Netherlands, Norway, Spain, Sweden, Switzerland, United Kingdom