OncoMatch/Clinical Trials/NCT05745714
HEM-iSMART-C: Ruxolitinib + Venetoclax + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric Patients With Relapsed or Refractory Hematological Malignancies
Is NCT05745714 recruiting? Yes, currently enrolling (May 2026). This Phase 1/2 trial studies multiple treatments for acute lymphoblastic leukemia, in relapse.
Treatment: Ruxolitinib · Venetoclax · 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 C is a phase I/II trial evaluating the safety and efficacy of ruxolitinib and venetoclax in combination with dexamethasone, cyclophosphamide and cytarabine in children and AYA with R/R ped ALL/LBL whose tumor present with alterations in the IL7R/JAK-STAT pathway.
Check if I qualifyExtracted eligibility criteria
Cancer type
Acute Lymphoblastic Leukemia
Non-Hodgkin Lymphoma
Biomarker criteria
Allowed: CRLF2 rearrangement
CRLF2: Rearrangements and mutations leading to CRLF2 overexpression (P2RY8-CRLF2, IGH-CRLF2, and CRLF2 F232C), CRFL2 overexpression
Allowed: CRLF2 mutation
CRLF2: Rearrangements and mutations leading to CRLF2 overexpression (P2RY8-CRLF2, IGH-CRLF2, and CRLF2 F232C), CRFL2 overexpression
Allowed: CRLF2 overexpression
CRLF2: Rearrangements and mutations leading to CRLF2 overexpression (P2RY8-CRLF2, IGH-CRLF2, and CRLF2 F232C), CRFL2 overexpression
Allowed: EPOR truncating rearrangement
EPOR: Truncating rearrangements or mutations in exon 8, EPOR fusions
Allowed: EPOR mutation in exon 8
EPOR: Truncating rearrangements or mutations in exon 8, EPOR fusions
Allowed: EPOR fusion
EPOR: Truncating rearrangements or mutations in exon 8, EPOR fusions
Allowed: JAK1 missense mutation
JAK1/2/3: Recurrent or novel missense and in-frame indel mutations in or flanking the pseudokinase and kinase domains, JAK fusion
Allowed: JAK1 in-frame indel mutation
JAK1/2/3: Recurrent or novel missense and in-frame indel mutations in or flanking the pseudokinase and kinase domains, JAK fusion
Allowed: JAK2 missense mutation
JAK1/2/3: Recurrent or novel missense and in-frame indel mutations in or flanking the pseudokinase and kinase domains, JAK fusion
Allowed: JAK2 in-frame indel mutation
JAK1/2/3: Recurrent or novel missense and in-frame indel mutations in or flanking the pseudokinase and kinase domains, JAK fusion
Allowed: JAK2 fusion
JAK1/2/3: Recurrent or novel missense and in-frame indel mutations in or flanking the pseudokinase and kinase domains, JAK fusion
Allowed: JAK3 missense mutation
JAK1/2/3: Recurrent or novel missense and in-frame indel mutations in or flanking the pseudokinase and kinase domains, JAK fusion
Allowed: JAK3 in-frame indel mutation
JAK1/2/3: Recurrent or novel missense and in-frame indel mutations in or flanking the pseudokinase and kinase domains, JAK fusion
Allowed: JAK3 fusion
JAK1/2/3: Recurrent or novel missense and in-frame indel mutations in or flanking the pseudokinase and kinase domains, JAK fusion
Allowed: IL7R missense mutation
IL7R: Recurrent or novel missense or in-frame indel mutations in the transmembrane domain; IL7R mutations
Allowed: IL7R in-frame indel mutation
IL7R: Recurrent or novel missense or in-frame indel mutations in the transmembrane domain; IL7R mutations
Allowed: IL7R mutation
IL7R: Recurrent or novel missense or in-frame indel mutations in the transmembrane domain; IL7R mutations
Allowed: SH2B3 copy number deletion
SH2B3: Copy number deletions, or mutations that result in frameshifts or premature termination
Allowed: SH2B3 frameshift mutation
SH2B3: Copy number deletions, or mutations that result in frameshifts or premature termination
Allowed: SH2B3 premature termination mutation
SH2B3: Copy number deletions, or mutations that result in frameshifts or premature termination
Allowed: USP9X truncating mutation
USP9X truncating mutation or USP9X-DDX3X fusion
Allowed: USP9X USP9X-DDX3X fusion
USP9X truncating mutation or USP9X-DDX3X fusion
Allowed: STAT5B mutation
STAT5B and DNM2 mutations
Allowed: DNM2 mutation
STAT5B and DNM2 mutations
Allowed: PTPN2 deletion
PTPN2 deletion described as involved in IL7R/JAK/STAT pathway activation
Prior therapy
Cannot have received: ruxolitinib and venetoclax in combination (ruxolitinib, venetoclax)
Exception: Patients who have previously received any of these two drugs separately can be eligible for this sub-protocol
Previous treatment with ruxolitinib and venetoclax in combination
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 discussion with sponsor.
Cardiac function
Shortening fraction (SF) >29% (>35% for children < 3 years) and/or LVEF ≥50% at baseline; Absence of QTcF prolongation (>450 msec on baseline ECG, Friedericia correction), or other clinically significant ventricular or atrial arrhythmia
Adequate organ function: RENAL AND HEPATIC FUNCTION...CARDIAC FUNCTION...
Structured fields extracted by AI. May contain errors — verify against the official protocol.
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