OncoMatch/Clinical Trials/NCT05658640
HEM iSMART-D: Trametinib + Dexamethasone + Chemotherapy in Children With Relapsed or Refractory Hematological Malignancies
Is NCT05658640 recruiting? Yes, currently enrolling (Jun 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
Treatments studied
Targeted therapy
Chemotherapy
Other
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
Demographics
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.
Frequently asked questions
Is NCT05658640 currently recruiting?
Yes, this trial is currently recruiting patients.
Are there prior therapy exclusions?
Yes. Prior MEK inhibitor disqualifies patients from enrollment.
Does this trial require KRAS?
Yes, KRAS activating mutation is a required biomarker for enrollment.
Does this trial require NRAS?
Yes, NRAS activating mutation is a required biomarker for enrollment.
Does this trial require HRAS?
Yes, HRAS activating mutation is a required biomarker for enrollment.
Is there an age limit?
Yes. Patients must be 21 years or younger and at least 1 years old.
Could you qualify for this trial?
Enter your biomarker results to see how this trial's eligibility criteria match your specific cancer profile.
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