RecruitingPhase 1Phase 2NCT05745714

HEM-iSMART-C: Ruxolitinib + Venetoclax + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric Patients 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 C Ruxolitinib + Venetoclax + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric Patients With Relapsed or Refractory Hematological Malignancies

Sponsor

Princess Maxima Center for Pediatric Oncology

Enrollment

26 participants

Start Date

Oct 1, 2025

Study Type

INTERVENTIONAL

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

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 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.

Eligibility

Min Age: 1 YearMax Age: 21 Years

Plain Language Summary

Simplified for easier understanding

This study is testing a combination of cancer drugs — ruxolitinib, venetoclax, dexamethasone, cyclophosphamide, and cytarabine — for children and young adults whose blood cancer (leukemia or lymphoma) has come back or stopped responding to treatment. The drugs target specific genetic changes in the cancer. **You may be eligible if...** - You are between 1 and 21 years old (diagnosed before age 18) - Your cancer has specific genetic changes in the JAK-STAT signaling pathway (identified by advanced genetic testing) - Your leukemia or lymphoma has relapsed or is not responding to standard treatment - Your general health and functioning level meets the study threshold (Karnofsky or Lansky score ≥50%) **You may NOT be eligible if...** - Your cancer does not have the specific genetic changes this drug targets - You have not had advanced molecular profiling of your cancer done - Your overall health is too poor to tolerate treatment - Your parents/guardians are unable to provide consent Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGRuxolitinib

oral

DRUGVenetoclax

oral

DRUGDexamethasone

oral/intravenous

DRUGCyclophosphamide

intravenous

DRUGCytarabine

intravenous

DRUGintrathecal chemotherapy

IT: Methotrexate +/- prednisone/hydrocortisone/cytarabine according to the degree of central nervous involvement

Locations(33)

St. Anna Kinderspital

Vienna, Austria

Universitair Ziekenhuis Gent

Ghent, Belgium

Rigshospitalet Copenhagen

Copenhagen, Denmark

Helsinki University Hospital, New Children's Hospital

Helsinki, Finland

Hôpital des Enfants GH Pellegrin - CHU de Bordeaux

Bordeaux, France

CHRU Lille - Hôpital Jeanne de Flandre

Lille, France

Centre Léon Bérard

Lyon, France

Hopital La Timone - Enfants

Marseille, France

CHU Nantes Hôpital Mère-Enfant

Nantes, France

Hôpital Robert Debré

Paris, France

Universitätsklinikum Augsburg

Augsburg, Germany

Charité Universitätsmedizin Berlin

Berlin, Germany

Universitätsklinikum Essen

Essen, Germany

Universitätsklinikum Frankfurt

Frankfurt, Germany

Universitätsklinikum Münster

Münster, Germany

Our Lady's Hospital for Sick Children

Dublin, Ireland

Schneider's Children's Medical Center

Petah Tikva, Israel

Sheba Medical Center Hospital

Ramat Gan, Israel

IRCCS Istituto Giannina Gaslini

Genova, Italy

Fondazione MBBM c/o Centro ML Verga

Monza, Italy

Padova Azienda Ospedaliera

Padova, Italy

Ospedale Pediatrico Bambino Gesù, IRCCS

Roma, Italy

Ospedale Infantile Regina Margherita

Turin, Italy

Princess Máxima Center for Pediatric Oncology

Utrecht, Utrecht, Netherlands

Oslo University Hospital

Oslo, Norway

Hospital Sant Joan de Déu de Barcelona

Barcelona, Spain

Hospital Infantil Universitario Niño Jesús

Madrid, Spain

La Fe

Valencia, Spain

Karolinska university hospital

Stockholm, Sweden

Bristol Royal Hospital for Children

Bristol, United Kingdom

Great Ormond Street Hospital for Children NHS Trust

London, United Kingdom

Great North Children's Hospital

Newcastle, United Kingdom

Royal Marsden NHS Trust

Sutton, United Kingdom

View Full Details on ClinicalTrials.gov

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NCT05745714

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