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11.09.2023 | Original Research Article

Azacitidine (Vidaza^®) in Pediatric Patients with Relapsed Advanced MDS and JMML: Results of a Phase I/II Study by the ITCC Consortium and the EWOG-MDS Group (Study ITCC-015)

verfasst von: Alba Rubio-San-Simón, Natasha K. A. van Eijkelenburg, Raoull Hoogendijk, Henrik Hasle, Charlotte M. Niemeyer, Michael N. Dworzak, Marco Zecca, Marta Lopez-Yurda, Julie M. Janssen, Alwin D. R. Huitema, Marry M. van den Heuvel-Eibrink, Eric J. Laille, Harm van Tinteren, Christian M. Zwaan

Erschienen in: Pediatric Drugs | Ausgabe 6/2023

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Abstract

Background

Advanced myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukemia (JMML) are rare hematological malignancies in children. A second allograft is recommended if a relapse occurs after hematopoietic stem cell transplantation, but the outcome is poor.

Objective

We conducted a phase I/II multicenter study to evaluate the safety, pharmacokinetics, and activity of azacitidine in children with relapsed MDS/JMML prior to the second hematopoietic stem cell transplantation.

Methods

Patients enrolled from June 2013 to March 2019 received azacitidine intravenously/subcutaneously once daily on days 1–7 of a 28-day cycle. The MDS and JMML cohorts followed a two-stage design separately, with a safety run-in for JMML. Response and safety data were used to evaluate efficacy and establish the recommended dose. Pharmacokinetics was also analyzed. The study closed prematurely because of low recruitment.

Results

Six patients with MDS and four patients with JMML received a median of three and five cycles, respectively. Azacitidine 75 mg/m² was well tolerated and plasma concentration–time profiles were similar to observed in adults. The most prevalent grade 3–4 adverse event was myelotoxicity. No responses were seen in patients with MDS, but 83% achieved stable disease; four patients underwent an allotransplant. Overall response rate in the JMML cohort was 75% (two complete responses; one partial response) and all responders underwent hematopoietic stem cell transplantation. One-year overall survival was 67% (95% confidence interval 38–100) in MDS and 50% (95% confidence interval 19–100) in JMML.

Conclusions

Azacitidine 75 mg/m² prior to a second hematopoietic stem cell transplantation is safe in children with relapsed MDS/JMML. Although the long-term advantage remains to be assessed, this study suggests that azacitidine is an efficacious option for relapsed JMML.

Clinical Trial Registration

EudraCT 2010-022235-10.

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Titel: Azacitidine (Vidaza®) in Pediatric Patients with Relapsed Advanced MDS and JMML: Results of a Phase I/II Study by the ITCC Consortium and the EWOG-MDS Group (Study ITCC-015)
verfasst von: Alba Rubio-San-Simón
Natasha K. A. van Eijkelenburg
Raoull Hoogendijk
Henrik Hasle
Charlotte M. Niemeyer
Michael N. Dworzak
Marco Zecca
Marta Lopez-Yurda
Julie M. Janssen
Alwin D. R. Huitema
Marry M. van den Heuvel-Eibrink
Eric J. Laille
Harm van Tinteren
Christian M. Zwaan
Publikationsdatum: 11.09.2023
Verlag: Springer International Publishing
Erschienen in: Pediatric Drugs / Ausgabe 6/2023
Print ISSN: 1174-5878
Elektronische ISSN: 1179-2019
DOI: https://doi.org/10.1007/s40272-023-00588-5

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Azacitidine (Vidaza^®) in Pediatric Patients with Relapsed Advanced MDS and JMML: Results of a Phase I/II Study by the ITCC Consortium and the EWOG-MDS Group (Study ITCC-015)