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Zwaan group

Our research program includes translational research projects in pediatric leukemia, with a special focus on experimental therapeutics/early drug development. The objective is to register new drugs for children with cancer so that they can be prescribed in the healthcare setting.

Group leader: Prof.dr. Michel Zwaan, pediatric oncologist
Phone +31 88 97 25 206
“We search for new medicines to increase survival rates
and decrease toxicity"
Prof. dr. Michel Zwaan - Group leader


As a pediatric oncologist, I am mainly concerned with the treatment of children with acute myeloid leukemia (AML) and related pre-clinical and clinical research, and with leukemia in children with Down syndrome.

In addition, I head the Trial and Data Center of the Princess Máxima Center, together with Dr. Harm van Tinteren, where I provide the medical expertise. I am general chair of the medical ethics review committee (METC) NedMec and of the NVMETC. I also chair the hematological malignancies committee of ITCC (phase 1-2 pediatric oncology network in Europe), for which the Maxima implements many studies.

Pre-clinical research

The research program on myeloid leukemias is done in close collaboration with group leaders in the Princess Máxima Center, including the Stam group, the Van Boxtel group and the Heidenreich group. The program focuses on identifying determinants of clinical outcome to improve risk-group stratification, and to identify novel options for targeted treatment. Down ALL projects are performed in close collaboration with the Den Boer group.

Close collaboration exists with Dr. Soheil Meshinchi from the Children’s Oncology Group (Seattle, USA), and Prof. Dirk Reinhardt from the AML-BFM Group (Essen, Germany), as well as with the International-BFM Study Group AML committee. 

 

PhD-student

In collaboration with

Project

Naomi Michels

Monique den Boer

Molecular aberrations in pediatric Down Syndrome Acute Lymphoblastic Leukemia

Fabienne Adriaanse

Tanja Gruber (St Jude), Ronald Stam

Mechanisms of HOX mediated leukemogenesis in Acute Myeloid Leukemia (AML)

Romy van Weelderen

Gertjan Kaspers, Bianca Goemans

Clinical aspects of pediatric AML   

Milad Rasouli

Olaf Heidenreich

Therapeutic targeting of the FUS/ERG fusion gene by siRNA delivery

Joost Koedijk

Olaf Heidenreich

Paving the way for an immune approach in pediatric AML

Alicia Perzolli

Olaf Heidenreich

Characterizing and manipulating the tumor immune microenvironment in pediatric acute myeloid leukemia

Elizabeth Schweighart

Olaf Heidenreich, Bianca Goemans

Monitoring treatment response and alteration to the microenvironment at the single cell level in pediatric acute myeloid leukemia



Clinical Research

The early clinical trial program includes clinical studies of promising novel agents for children with cancer, and in addition focuses on therapeutic drug monitoring, bioequivalence studies of pediatric-friendly formulations, and age-dependent pharmacokinetics/dynamics.

This includes looking at new drugs developed under a Pediatric Investigational Plan of the European Medicines Ageny. The following studies, involving Prof. Dr. Michel Zwaan as principal investigator, are currently ongoing in this context:

  • Inotuzumab ozogamicin (phase 1 and 2 studies in children with ALL)
  • Bosutinib (phase 1 and 2 studies in children with CML)
  • Crizotinib (a phase 4 study of dosing and toxicity of this drug as part of a registration requirement)
  • Brigatinib (a phase 1/2 study in children with solid tumors and large cell anaplastic lymphoma)
  • Venetoclax (a phase 3 study in children with relapsed AML)

Based on the first two studies, the FDA recently approved bosutinib for the treatment of newly diagnosed and resistant/intolerant children over 1 year of age with CML (September 2023), and inotuzumab ozogamicin for the treatment of children over one year of age with relapsed/refractory CD22-positive ALL (March 2024). These approvals were obtained after transfer of the data obtained in these intent-to-file academic studies to the pharma company, who submitted the dossier to the regulatory authorities for assessment. The opinion of the European and Japanese health authorities is awaited.

In addition, the Trial and Data Center is closely involved in two new leukemia studies initiated from the Máxima:

  • The CHIP-AML study for newly diagnosed children with AML. As a subtrial, this involves studying quizartinib in FLT3 mutated patients as part of a pediatric investigational plan (principal investigator Prof. Dr. Gertjan Kaspers).
  • The Interfant-21 study, studying blinatumomab (principal investigators Dr. Janine Stutterheim and Prof. Dr. Rob Pieters).



Research (clinical scientists) into pediatric drug development 

  • Erica Brivio
  • Sae Ishimaru
  • Paco Bautista


Hematological malignancies Unit


Solid tumor Unit
 
Dannis van Vuurden (pontine glioma)

PhD students


PhD student

In collaboration with

Project

Uri Ilan

Monique den Boer, Judith Boer

European international leukemia tumor board and Hem-SMART clinical trial platform

Eduardo Pennesi

Alwin Huitema

Early clinical trials in children with leukemia

Eric Wu

Paco Bautista, Alwin Huitema

Pharmacokinetic modelling for anti-cancer drugs in pediatric oncology to guide dose optimization

Kim Schellekens

Reineke Schoot

Studies in ALK-rearranged tumors and supportive care

Valeria Ceolin

Bianca Goemans, Nicoletta Bertorello (Turijn, Italië)

Early phase clinical trials in pediatric oncology

Emma Geerdes

Marc Raaijmakers, Henrike Karim-Kos, Maya Schulpen

Pediatric and young adult leukemia


 




Zwaan group