HEM-iSMART-A: Decitabine / Venetoclax and Navitoclax in Pediatric Patients With Relapsed or Refractory Hematological Malignancies

Sponsor
Princess Maxima Center for Pediatric Oncology
Study ID
NCT05740449
Phase
PHASE1/PHASE2
Status
Withdrawn

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

  • Decitabine — DRUG
    intravenous
  • Venetoclax — DRUG
    oral
  • Navitoclax — DRUG
    oral
  • 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 A is a phase I/II trial evaluating the safety and efficacy of Decitabine / Venetoclax and Navitoclax in children and AYA with R/R pediatric ALL/LBL

Key Dates

Start date
Oct 1, 2023
Status verified
Jun 2024
Primary completion
Oct 1, 2029
Completion
Oct 1, 2029

Study Design

Enrollment
0 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: sub-study A - Epigenetic approach
    Decitabine / Venetoclax and Navitoclax. Each cycle lasts 28 days. Cycle 1: Decitabine is given 10 mg/m2 intravenous, once a day on 5 consecutive days (Day 1 - 5), venetoclax 400 mg adult equivalent dose, once a day, Day 1 - Day 28 orally, with a ramp-up dose on day 1 and navitoclax once a day, Day 3 - 28 orally depending on the weight of the patient (dose level 1). Cycle 2: Decitabine is given 10 mg/m2 intravenous, once a day on 5 consecutive days (Day 1 - 5), venetoclax 400 mg adult equivalent dose, once a day, Day 1 - Day 28 orally and navitoclax once a day, Day 1 - 28 orally depending on the weight of the patient (dose level 1). Patients in dose level 2: will receive decitabine 20 mg/m2 intravenous once a day on 5 consecutive days (Day 1 - 5). Patients in dose level -1: will receive venetoclax 200 mg adult equivalent dose, once a day, Day 1 - Day 28 orally. All patients receive age adapted intrathecal chemnotherapy.

Primary Outcome Measure

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

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