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HEM-iSMART E: Capivasertib + Venetoclax + Dexamethasone in Pediatric Patients With Relapsed or Refractory Hematological Malignancies | Clinical Trials | Clareo Health

NOT_YET_RECRUITINGPHASE1/PHASE2

HEM-iSMART E: Capivasertib + Venetoclax + Dexamethasone in Pediatric Patients With Relapsed or Refractory Hematological Malignancies

ITCC-104: HEM-iSMART International Proof of Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory HEMatological Malignancies in Children, Sub-Protocol E: Capivasertib + Venetoclax + Dexamethasone in Pediatric Patients With Relapsed or Refractory Hematological Malignancies

NCT07175415•Princess Maxima Center for Pediatric Oncology

View on ClinicalTrials.gov

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 E is a phase I/II trial evaluating the safety and efficacy of capivasertib + venetocolax in combination with dexamethasone in children and AYA with R/R ped ALL/LBL whose tumor present with alterations of the PAM pathway, or lacking any mutations.

Detailed Description

HEM-iSMART is a master protocol with sub-protocols. The overarching objective is that introducing targeted therapy using a biomarker driven approach for treatment stratification may improve the outcome of children with R/R acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) It is characterized by a shared framework that allows for the investigation of multiple IMPs and generate pivotal safety and efficacy evidence within the sub-protocols to establish and define the benefits and risks of new treatments for children with R/R leukemia. Sub-protocol E within HEM-iSMART is a phase I/II, multicenter, international, open-label clinical trial designed to evaluate the safety, tolerability, pharmacokinetics (PK) and efficacy of capivasertib + venetoclax in combination with dexamethasone in children, adolescents and young adults with relapsed or refractory (R/R) hematological malignancies including ALL and LBL. Patients in must present alterations of the PAM pathway, or can be enrolled on a generic base lacking any mutations.

Eligibility

Age

2 - 21 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Children ≥ 2 years and ≤ 18 years of age at the time of first diagnosis and less than 21 years at the time of inclusion
•2. Performance status: Karnofsky performance status (for patients \>16 years of age) or Lansky Play score (for patients ≤16 years of age) ≥ 50% (Appendix I).
•3. Written informed consent from parents/legal representative, patient, and age-appropriate assent before any study specific screening procedures are conducted, according to local, regional or national guidelines.
•4. For all oral medications patients must be able to comfortably swallow tablets (except for those for which the AAF is available; nasogastric or gastrostomy feeding tube administration is allowed only if indicated).
•5. Patients must have had advanced molecular profiling and flow-cytometric analysis of their recurrent or refractory disease at a time-point before the first inclusion into this trial (see section 9.1 of the master protocol for detailed description of the molecular diagnostics required). Drug response profiling and methylation is highly recommended but not mandatory. Patients with advanced molecular profiling at diagnosis may be allowed to be included after discussion with the sponsor.
•6. In the Phase II portion of the trial, 30% of the eligible patients will have to show alterations in the PI3K/AKT/mTOR pathway as follows: PI3K (including PIK3CA, PIK3CB, PIK3R1), AKT and loss of PTEN.
•7. Patients with spinal cord compression should be deemed clinically stable prior to enrolment into the trial.
•8. Adequate organ function:
•RENAL AND HEPATIC FUNCTION (Assessed within 48 hours prior to C1D1):
•Serum creatinine ≤ 1.5 x upper limit of normal (ULN) for age or calculated creatinine clearance as per the Schwartz formula or radioisotope glomerular filtration rate ≥ 60 mL/min/1.73 m2.
+5 more criteria

Exclusion Criteria

•1. Pregnancy or positive pregnancy test (urine or serum) in females of childbearing potential. Pregnancy test must be performed within 7 days prior to C1D1.
•2. Sexually active participants of childbearing potential not willing to use highly effective contraceptive method (pearl index \<1) as defined in CTFG HMA 2020 (Appendix II) during trial participation and until 30 days after end of study intervention for females and 16 weeks for males.
•3. Breast feeding.
•4. History of another primary malignancy.
•5. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome) in case of oral IMPs.
•6. Patients whose tumor present known mutations conferring resistance to venetoclax (e.g. BCL2 mutations of venetoclax binding-site (Gly101Val mutation, Phe104Leu/Cys mutations) and capivasertib (e.g. mutations in TSC1, TSC2 and STK11).
•7. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to the study drugs, or drugs chemically related to study treatment or excipients that contraindicate their participation, including corticoids.
•8. Known active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection.
•9. Severe concomitant disease that does not allow treatment according to the protocol at the investigator's discretion.
•10. Subjects unwilling or unable to comply with the study procedures.
+16 more criteria

Key Dates

Start Date

October 1, 2026

Primary Completion Date

October 1, 2031

Completion Date

October 1, 2032

Last Updated

September 16, 2025

Enrollment

ESTIMATED participants

Conditions

Acute Lymphoblastic LeukemiaLymphoblastic Lymphoma (Precursor B-Lymphoblastic Lymphoma/Leukaemia) RecurrentLymphoblastic Lymphoma (Precursor B-Lymphoblastic Lymphoma/Leukaemia) RefractoryLymphoblastic Lymphoma (Precursor T-Lymphoblastic Lymphoma/Leukaemia) RecurrentLymphoblastic Lymphoma (Precursor T-Lymphoblastic Lymphoma/Leukaemia) Refractory

Interventions

Capivasertib

DRUG

Venetoclax

DRUG

Dexamethasone

DEVICE

Intrathecal chemotherapy

DRUG

Contacts

Anne Elsinghorst Elsinghorst

CONTACT

+31650006270 hem-ismart@prinsesmaximacentrum.nl

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: September 16, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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HEM-iSMART E: Capivasertib + Venetoclax + Dexamethasone in Pediatric Patients With Relapsed or Refractory Hematological Malignancies

Inclusion Criteria

Exclusion Criteria

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