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

ConditionsAcute 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
Trial statusNot yet recruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age2-21
SponsorPrincess Maxima Center for Pediatric Oncology

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Children ≥ 2 years and ≤ 18 years of age at the time of first diagnosis and less than 21 years at the time of inclusion

Performance status: Karnofsky performance status (for patients >16 years of age) or Lansky Play score (for patients ≤16 years of age) ≥ 50% (Appendix I).

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.

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).

Disqualifiers

Pregnancy or positive pregnancy test (urine or serum) in females of childbearing potential. Pregnancy test must be performed within 7 days prior to C1D1.

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.

Breast feeding.

History of another primary malignancy.

Trial design

Design model

Single group

Treatments tested in this trial

  • Capivasertib

    Drug

    Oral

  • Venetoclax

    Drug

    Oral

  • Dexamethasone

    Device

    oral/intravenous

  • Intrathecal chemotherapy

    Drug

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

Treatment groups

42 Participants
are divided into 1 treatment group
Group A: Capivasertib + Venetoclax + DexamethasoneExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

Phase I: Maximum tolerated dose (MTD) / Recommended phase 2 dose (RP2D).

Defined as the highest dose level tested at which 0/6 or 1/6 patients experiences dose limiting toxicities (DLT) during course 1 with at least 2 patients experiencing DLT at the next higher dose.

Time frame
2 years
2

Phase II: Best Overall Response Rate (ORR).

For patients with leukemia: CR and MRD response after 1 cycle of treatment. This includes determination of CR, CRp, CRi and minimal residual disease (MRD) negativity rate in patients suffering from overt morphological relapse of T-ALL at time of enrolment (morphological disease (M2/M3)), and the MRD negativity rate in those that entered with high-MRD levels but in morphological CR. These results will together be presented as a composite endpoint Overall Response rate (ORR). MRD negativity will be defined as ≤1x10-4 as generated by multi-parameter flow cytometry. For patients with lymphoma: Response in LBL patients is defined as CR, PR, minor response (MR) as defined in International pediatric NHL response criteria. In case of bone-marrow involvement MRD will be taken into account. For patients with lymphoma: Response in LBL patients is defined as CR, PR, minor response (MR) as defined in International pediatric NHL response criteria.

Time frame
4 years

Secondary outcomes

1

Overall survival (OS)

Defined as time from C1D1 until death of any cause.

Time frame
5 years
2

Event-free survival (EFS)

Defined as time from C1D1 to the first event (subsequent relapse after CR (including molecular reappearance), death of any cause, failure to achieve remission (CR, CRp or CRi), or secondary malignancy).

Time frame
5 years
3

Cumulative incidence of relapse (CIR)

Estimate of the risk, that a patient will develop a relapse over a specified period of time.

Time frame
5 years
4

Number of patients proceeding to hematopoietic stem cell transplantation (HSCT) after the experimental therapy.

The rate of those proceeding to subsequent allogenic HSC

Time frame
5 years

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Princess Maxima Center for Pediatric Oncology

Lead sponsor

AstraZeneca

Collaborator

AbbVie

Collaborator

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: