Zwaan group

Group leader: Prof.dr. Michel Zwaan, pediatric oncologist

“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. 

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)

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

• Inge van der Sluis
• Britta Vormoor
• Auke Beishuizen (lymphoma)
• Caroline Lindemans (SCT)
• Maaike Luesink

• Natasha van Eijkelenburg
• Miranda Dierselhuis (fellow pediatric oncology)
  
  Brain tumor Unit
• Jasper van der Lugt
• Eveline de Vos
• Dannis van Vuurden (pontine glioma)
  
  PhD students
  
  

  PhD student In collaboration with Project Erica Brivio Monique den Boer, Vincent van der Velden Pediatric leukemia: new treatment opportunities and supportive care studies 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

  
  

   

  Key publications

  Gore L, Kearns PR, de Martino Lee ML, De Souza CA, Bertrand Y, Hijiya N, Stork LC, Chung NG, Cardos RC, Saikia T, Fagioli F, Seo JJ, Landman-Parker J, Lancaster D, Place AE, Rabin KR, Sacchi M, Swanink R, Zwaan CM. Dasatinib in Pediatric Patients With Chronic Myeloid Leukemia in Chronic Phase: Results From a Phase II Trial. J Clin Oncol. 2018 May 1;36(13):1330-1338PubMed PMID: 29498925
  
  Van Eijkelenburg NKA, Rasche M, Ghazaly E, Dworzak MN, Klingebiel T, Rossig C, Leverger G, Stary J, de Bont ESJM, Chitu DA, Bertrand Y, Brethon B, Strahm B, van der Sluis IM, Kaspers GJL, Reinhardt D, Zwaan CM. Clofarabine, high-dose cytarabine and liposomal daunorubicin in pediatric relapsed/refractory acute myeloid leukemia: a phase IB study. Haematologica. 2018 Sep;103(9):1484-1492 PubMed PMID: 29773602

  Bolouri H, Farrar JE, Triche T Jr, Ries RE, Lim EL, Alonzo TA, Ma Y, Moore R, Mungall AJ, Marra MA, Zhang J, Ma X, Liu Y, Liu Y, Auvil JMG, Davidsen TM, Gesuwan P, Hermida LC, Salhia B, Capone S, Ramsingh G, Zwaan CM, Noort S, Piccolo SR, Kolb EA, Gamis AS, Smith MA, Gerhard DS, Meshinchi S. The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions. Nat Med. 2018:Jan 24(1):103-112 PubMed PMID: 29227476 

  Moreno L, Pearson ADJ, Paoletti X, Jimenez I, Geoerger B, Kearns PR, Zwaan CM, Doz F, Baruchel A, Vormoor J, Casanova M, Pfister SM, Morland B, Vassal G; Innovative Therapies for Children with Cancer (ITCC) Consortium. Early phase clinical trials of anticancer agents in children and adolescents - an ITCC perspective. Nat Rev Clin Oncol. 2017 Aug;14(8):497-507 PubMed PMID: 28508875

  Pearson ADJ, Pfister SM, Baruchel A, Bourquin JP, Casanova M, Chesler L, Doz F, Eggert A, Geoerger B, Jones DTW, Kearns PR, Molenaar JJ, Morland B, Schleiermacher G, Schulte JH, Vormoor J, Marshall LV, Zwaan CM, Vassal G; Executive and Biology Committees of the Innovative Therapies for Children with Cancer European Consortium. From class waivers to precision medicine in paediatric oncology. Lancet Oncol. 2017 Jul;18(7):e394-e404 PubMed PMID: 28677575 

  Madita Uffmann, Mareike Rasche, Martin Zimmermann, Christine von Neuhoff, Ursula Creutzig, Michael Dworzak, Lenie Scheffers, Henrik Hasle, C. Michel Zwaan, Dirk Reinhardt, and Jan-Henning Klusmann. Therapy reduction in patients with Down Syndrome Myeloid Leukemia: The international ML-DS 2006 trial. Blood 2017 Jun 22;129(25):3314-3321 PubMed PMID: 28400376

  De Rooij JD, Branstetter C, Ma J, Li Y, Walsh MP, Cheng J, Obulkasim A, Dang J, Easton J, Verboon LJ, Mulder HL, Zimmermann M, Koss C, Gupta P, Edmonson M, Rusch M, Lim JY, Reinhardt K, Pigazzi M, Song G, Yeoh AE, Shih LY, Liang DC, Halene S, Krause DS, Zhang J, Downing JR, Locatelli F, Reinhardt D, van den Heuvel-Eibrink MM, Zwaan CM, Fornerod M, Gruber TA. Pediatric non-Down syndrome acute megakaryoblastic leukemia is characterized by distinct genomic subsets with varying outcomes. Nat Genet. 2017 Mar;49(3):451-456 PubMed PMID: 28112737

  Arend von Stackelberg, Franco Locatelli, Gerhard Zugmaier, Rupert Handgretinger, Tanya M. Trippett, Carmelo Rizzari, Peter Bader, Maureen M. O’Brien, Benoˆıt Brethon, Deepa Bhojwani, Paul Gerhardt Schlegel, Arndt Borkhardt, Susan R. Rheingold, Todd Michael Cooper, Christian M. Zwaan, Phillip Barnette, Chiara Messina, Gerard Michel, Steven G. DuBois, Kuolung Hu, Min Zhu, James A. Whitlock, and Lia Gore. Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia. J Clin Oncol. 2016 Dec 20;34(36):4381-4389 PubMed PMID: 27998223 

  Zwaan CM, Kolb EA, Reinhardt D, Abrahamsson J, Adachi S, Aplenc R, De Bont ES, De Moerloose B, Dworzak M, Gibson BE, Hasle H, Leverger G, Locatelli F, Ragu C, Ribeiro RC, Rizzari C, Rubnitz JE, Smith OP, Sung L, Tomizawa D, van den Heuvel-Eibrink MM, Creutzig U, Kaspers GJ. Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia. J Clin Oncol. 2015 Sep 20;33(27):2949-62 PubMed PMID: 26304895

  Kang HJ, Loftus S, Taylor A, DiCristina C, Green S, Zwaan CM. Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in children: a randomised, double-blind, phase 3 trial. Lancet Oncol. 2015 Apr;16(4):385-94 PubMed PMID: 25770814

  Buitenkamp TD, Izraeli S, Zimmermann M, Forestier E, Heerema NA, van den Heuvel-Eibrink MM, Pieters R, Korbijn CM, Silverman LB, Schmiegelow K, Liang DC, Horibe K, Arico M, Biondi A, Basso G, Rabin KR, Schrappe M, Cario G, Mann G, Morak M, Panzer-Grümayer R, Mondelaers V, Lammens T, Cavé H, Stark B, Ganmore I, Moorman AV, Vora A, Hunger SP, Pui CH, Mullighan CG, Manabe A, Escherich G, Kowalczyk JR, Whitlock JA, Zwaan CM. Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno study group. Blood. 2014 Jan 2;123(1):70-7 PubMed PMID: 24222333
  
  Prof. Dr. Michel Zwaan's publications can be found on PubMed.