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

Sponsor
Princess Maxima Center for Pediatric Oncology
Study ID
NCT05745714
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • Acute Lymphoblastic Leukemia, in Relapse
  • Lymphoblastic Lymphoma (Precursor B-Lymphoblastic Lymphoma/Leukaemia) Recurrent
  • Lymphoblastic Lymphoma (Precursor B-Lymphoblastic Lymphoma/Leukaemia) Refractory
  • Lymphoblastic Lymphoma (Precursor T-Lymphoblastic Lymphoma/Leukaemia) Recurrent
  • Lymphoblastic Lymphoma (Precursor T-Lymphoblastic Lymphoma/Leukaemia) Refractory

Eligibility Criteria

Sex
ALL
Age
1 Year - 21 Years
Healthy Volunteers
Not accepted

Interventions

  • Ruxolitinib — DRUG
    oral
  • Venetoclax — DRUG
    oral
  • Dexamethasone — DRUG
    oral/intravenous
  • Cyclophosphamide — DRUG
    intravenous
  • Cytarabine — DRUG
    intravenous
  • intrathecal chemotherapy — DRUG
    IT: Methotrexate +/- prednisone/hydrocortisone/cytarabine according to the degree of central nervous involvement

Study Details

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.

Key Dates

Start date
Oct 1, 2025
Status verified
Sep 2025
Primary completion
Feb 1, 2032
Completion
Feb 2, 2032

Study Design

Enrollment
26 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Ruxolitinib + venetoclax + dexamethasone + cyclophosphamide + cytarabine
    Each cycle has 28 days Cycle 1: All patients will receive 14 days of of ruxolitinib (days 1-14), 28 days of venetoclax (days 1-28), one block of five days of dexamethasone (days 1-5), one dose of cyclophosphamide (day 3) and two blocks of four consecutive days of cytarabine (days 5 to 8 and days 12 to 15). A 1-day venetoclax ramp-up is proposed in this study. Cycle 2 and subsequent cycles: All patients will receive 14 days of of ruxolitinib (days 1-14), 28 days of venetoclax (days 1-28), one block of five days of dexamethasone (days 1-5), one dose of cyclophosphamide (day 1) and two blocks of four consecutive days of cytarabine (days 3 to 6 and days 10 to 13). Patients in dose level -1, will receive a lower dose of venetoclax compared to dose level 1. Patients in dose level 2, will receive a higher dose of venetoclax compared to dose level 1. All patients receive age adapted intrathecal chemotherapy.

Primary Outcome Measure

Phase I: Maximum tolerated dose (MTD) / Recommended phase 2 dose (RP2D) [ Time Frame: 3 years ]

Central Contacts

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