OncoMatch/Clinical Trials/NCT05658640
HEM iSMART-D: Trametinib + Dexamethasone + Chemotherapy in Children With Relapsed or Refractory Hematological Malignancies
Is NCT05658640 recruiting? Yes, currently enrolling (May 2026). This Phase 1/2 trial studies multiple treatments for acute lymphoblastic leukemia, in relapse.
Treatment: Trametinib · Dexamethasone · Cyclophosphamide · Cytarabine · Intrathecal chemotherapy — 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.
Check if I qualifyExtracted eligibility criteria
Cancer type
Acute Lymphoblastic Leukemia
Non-Hodgkin Lymphoma
Biomarker criteria
Required: KRAS activating mutation
RAS pathway activating mutations including but not limited to KRAS, NRAS, HRAS, FLT3, PTPN11, MAP2K1, MP2K1 hotspot mutations, cCBL; NF1 del
Required: NRAS activating mutation
RAS pathway activating mutations including but not limited to KRAS, NRAS, HRAS, FLT3, PTPN11, MAP2K1, MP2K1 hotspot mutations, cCBL; NF1 del
Required: HRAS activating mutation
RAS pathway activating mutations including but not limited to KRAS, NRAS, HRAS, FLT3, PTPN11, MAP2K1, MP2K1 hotspot mutations, cCBL; NF1 del
Required: FLT3 activating mutation
RAS pathway activating mutations including but not limited to KRAS, NRAS, HRAS, FLT3, PTPN11, MAP2K1, MP2K1 hotspot mutations, cCBL; NF1 del
Required: PTPN11 activating mutation
RAS pathway activating mutations including but not limited to KRAS, NRAS, HRAS, FLT3, PTPN11, MAP2K1, MP2K1 hotspot mutations, cCBL; NF1 del
Required: MAP2K1 hotspot mutation
RAS pathway activating mutations including but not limited to KRAS, NRAS, HRAS, FLT3, PTPN11, MAP2K1, MP2K1 hotspot mutations, cCBL; NF1 del
Required: MP2K1 hotspot mutation
RAS pathway activating mutations including but not limited to KRAS, NRAS, HRAS, FLT3, PTPN11, MAP2K1, MP2K1 hotspot mutations, cCBL; NF1 del
Required: CBL activating mutation
RAS pathway activating mutations including but not limited to KRAS, NRAS, HRAS, FLT3, PTPN11, MAP2K1, MP2K1 hotspot mutations, cCBL; NF1 del
Required: NF1 deletion
RAS pathway activating mutations including but not limited to KRAS, NRAS, HRAS, FLT3, PTPN11, MAP2K1, MP2K1 hotspot mutations, cCBL; NF1 del
Prior therapy
Cannot have received: MEK inhibitor (trametinib)
Previous treatment with trametinib
Lab requirements
Kidney function
Serum creatinine ≤ 1.5 x ULN for age or calculated creatinine clearance as per the Schwartz formula or radioisotope GFR ≥ 60 mL/min/1.73 m2
Liver function
Direct bilirubin ≤ 2 x ULN (≤ 3.0 × ULN for patients with Gilbert's syndrome); ALT/SGPT ≤ 5 x ULN; AST/SGOT ≤ 5 x ULN. Patients with hepatic dysfunction related to underlying disease may be eligible after sponsor discussion.
Cardiac function
Shortening fraction (SF) >29% (>35% for children < 3 years) and/or LVEF ≥50% at baseline by echocardiography or MUGA; absence of QTcF prolongation (>450 msec on baseline ECG, Fridericia correction), or other clinically significant ventricular or atrial arrhythmia
RENAL AND HEPATIC FUNCTION (Assessed within 48 hours prior to C1D1): Serum creatinine ≤ 1.5 x ULN for age or calculated creatinine clearance as per the Schwartz formula or radioisotope GFR ≥ 60 mL/min/1.73 m2. Direct bilirubin ≤ 2 x ULN (≤ 3.0 × ULN for patients with Gilbert's syndrome). ALT/SGPT ≤ 5 x ULN; AST/SGOT ≤ 5 x ULN. Patients with hepatic dysfunction related to underlying disease may be eligible after sponsor discussion. CARDIAC FUNCTION: SF >29% (>35% for children < 3 years) and/or LVEF ≥50% at baseline by echocardiography or MUGA; absence of QTcF prolongation (>450 msec on baseline ECG, Fridericia correction), or other clinically significant ventricular or atrial arrhythmia.
Structured fields extracted by AI. May contain errors — verify against the official protocol.
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