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 (Jun 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
Treatments studied
Targeted therapy
Chemotherapy
Other
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
Demographics
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.
Frequently asked questions
Is NCT05745714 currently recruiting?
Yes, this trial is currently recruiting patients.
Are there prior therapy exclusions?
Yes. Prior ruxolitinib and venetoclax in combination disqualifies patients from 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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