• Something wrong with this record ?

Response to upfront azacitidine in juvenile myelomonocytic leukemia in the AZA-JMML-001 trial

CM. Niemeyer, C. Flotho, DB. Lipka, J. Starý, C. Rössig, A. Baruchel, T. Klingebiel, C. Micalizzi, G. Michel, K. Nysom, S. Rives, M. Schmugge Liner, M. Zecca, M. Schönung, I. Baumann, P. Nöllke, B. Benettaib, N. Biserna, J. Poon, M. Simcock, M....

. 2021 ; 5 (14) : 2901-2908. [pub] 20210727

Language English Country United States

Document type Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc21025298

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for most children with juvenile myelomonocytic leukemia (JMML). Novel therapies controlling the disorder prior to HSCT are needed. We conducted a phase 2, multicenter, open-label study to evaluate the safety and antileukemic activity of azacitidine monotherapy prior to HSCT in newly diagnosed JMML patients. Eighteen patients enrolled from September 2015 to November 2017 were treated with azacitidine (75 mg/m2) administered IV once daily on days 1 to 7 of a 28-day cycle. The primary end point was the number of patients with clinical complete remission (cCR) or clinical partial remission (cPR) after 3 cycles of therapy. Pharmacokinetics, genome-wide DNA-methylation levels, and variant allele frequencies of leukemia-specific index mutations were also analyzed. Sixteen patients completed 3 cycles and 5 patients completed 6 cycles. After 3 cycles, 11 patients (61%) were in cPR and 7 (39%) had progressive disease. Six of 16 patients (38%) who needed platelet transfusions were transfusion-free after 3 cycles. All 7 patients with intermediate- or low-methylation signatures in genome-wide DNA-methylation studies achieved cPR. Seventeen patients received HSCT; 14 (82%) were leukemia-free at a median follow-up of 23.8 months (range, 7.0-39.3 months) after HSCT. Azacitidine was well tolerated and plasma concentration--time profiles were similar to observed profiles in adults. In conclusion, azacitidine monotherapy is a suitable option for children with newly diagnosed JMML. Although long-term safety and efficacy remain to be fully elucidated in this population, these data demonstrate that azacitidine provides valuable clinical benefit to JMML patients prior to HSCT. This trial was registered at www.clinicaltrials.gov as #NCT02447666.

Bristol Myers Squibb Princeton NJ

Bristol Myers Squibb San Francisco CA

Celgene Corporation a Bristol Myers Squibb company Uxbridge United Kingdom

Department of Paediatric Hematology and Oncology Charles University and University Hospital Motol Prague Czech Republic

Department of Paediatrics and Adolescent Medicine Rigshospitalet Copenhagen Denmark

Department of Pathology Böblingen Hospital Sindelfingen Germany

Department of Pediatric Hematology and Immunology Centre Hospitalier Universitaire Paris France

Department of Pediatric Hematology and Oncology IRCCS Ospedale Pediatrico Bambino Gesù Rome Italy

Department of Pediatric Hematology and Oncology Münster University Children's Hospital Münster Germany

Department of Pediatric Sciences Istituto Giannina Gaslini Istituto di Ricovero e Cura a Carattere Scientifico Genoa Italy

Department of Pediatrics Sapienza University of Rome Rome Italy

Department of Pediatrics Universitätsklinikum Frankfurt Frankfurt Germany

Division of Haematology Kinderspital Zürich Zürich Switzerland

Division of Pediatric Hematology and Oncology Department of Pediatrics and Adolescent Medicine Medical Center University of Freiburg Freiburg Germany

Faculty of Biosciences Heidelberg University Heidelberg Germany

Formerly Bristol Myers Squibb Princeton NJ

German Cancer Consortium Site Frankfurt Frankfurt Germany

German Cancer Research Center Heidelberg Germany

Hematology Oncology Prinses Máxima Center for Pediatric Oncology Hematology Utrecht The Netherlands

Pediatric Hematology and Oncology Institut de Recerca Hospital Sant Joan de Deu de Barcelona Barcelona Spain

Pediatric Hematology Oncology Fondazione IRCCS Policlinico San Matteo Pavia Italy

Pediatrics and Pediatric Oncology Hôpital de la Timone Marseilles France

Translational Cancer Epigenomics Section Division of Translational Medical Oncology German Cancer Research Center Heidelberg Germany

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc21025298
003      
CZ-PrNML
005      
20211026133939.0
007      
ta
008      
211013s2021 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1182/bloodadvances.2020004144 $2 doi
035    __
$a (PubMed)34297046
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Niemeyer, Charlotte M $u Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, University of Freiburg, Freiburg, Germany $u German Cancer Research Center (DKFZ), Heidelberg, Germany
245    10
$a Response to upfront azacitidine in juvenile myelomonocytic leukemia in the AZA-JMML-001 trial / $c CM. Niemeyer, C. Flotho, DB. Lipka, J. Starý, C. Rössig, A. Baruchel, T. Klingebiel, C. Micalizzi, G. Michel, K. Nysom, S. Rives, M. Schmugge Liner, M. Zecca, M. Schönung, I. Baumann, P. Nöllke, B. Benettaib, N. Biserna, J. Poon, M. Simcock, M. Patturajan, D. Menezes, A. Gaudy, MM. van den Heuvel-Eibrink, F. Locatelli
520    9_
$a Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for most children with juvenile myelomonocytic leukemia (JMML). Novel therapies controlling the disorder prior to HSCT are needed. We conducted a phase 2, multicenter, open-label study to evaluate the safety and antileukemic activity of azacitidine monotherapy prior to HSCT in newly diagnosed JMML patients. Eighteen patients enrolled from September 2015 to November 2017 were treated with azacitidine (75 mg/m2) administered IV once daily on days 1 to 7 of a 28-day cycle. The primary end point was the number of patients with clinical complete remission (cCR) or clinical partial remission (cPR) after 3 cycles of therapy. Pharmacokinetics, genome-wide DNA-methylation levels, and variant allele frequencies of leukemia-specific index mutations were also analyzed. Sixteen patients completed 3 cycles and 5 patients completed 6 cycles. After 3 cycles, 11 patients (61%) were in cPR and 7 (39%) had progressive disease. Six of 16 patients (38%) who needed platelet transfusions were transfusion-free after 3 cycles. All 7 patients with intermediate- or low-methylation signatures in genome-wide DNA-methylation studies achieved cPR. Seventeen patients received HSCT; 14 (82%) were leukemia-free at a median follow-up of 23.8 months (range, 7.0-39.3 months) after HSCT. Azacitidine was well tolerated and plasma concentration--time profiles were similar to observed profiles in adults. In conclusion, azacitidine monotherapy is a suitable option for children with newly diagnosed JMML. Although long-term safety and efficacy remain to be fully elucidated in this population, these data demonstrate that azacitidine provides valuable clinical benefit to JMML patients prior to HSCT. This trial was registered at www.clinicaltrials.gov as #NCT02447666.
650    _2
$a dospělí $7 D000328
650    _2
$a azacytidin $x škodlivé účinky $7 D001374
650    _2
$a dítě $7 D002648
650    _2
$a metylace DNA $7 D019175
650    12
$a transplantace hematopoetických kmenových buněk $7 D018380
650    _2
$a lidé $7 D006801
650    12
$a juvenilní myelomonocytární leukemie $x farmakoterapie $x genetika $7 D054429
650    _2
$a mutace $7 D009154
655    _2
$a klinické zkoušky, fáze II $7 D017427
655    _2
$a časopisecké články $7 D016428
655    _2
$a multicentrická studie $7 D016448
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Flotho, Christian $u Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, University of Freiburg, Freiburg, Germany $u German Cancer Research Center (DKFZ), Heidelberg, Germany
700    1_
$a Lipka, Daniel B $u Translational Cancer Epigenomics Section, Division of Translational Medical Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
700    1_
$a Starý, Jan $u Department of Paediatric Hematology and Oncology, Charles University and University Hospital Motol, Prague, Czech Republic
700    1_
$a Rössig, Claudia $u Department of Pediatric Hematology and Oncology, Münster University Children's Hospital, Münster, Germany
700    1_
$a Baruchel, André $u Department of Pediatric Hematology and Immunology, Centre Hospitalier Universitaire (CHU) Paris-Hôpital Universitaire Robert-Debré (Assistance Publique-Hôpitaux de Paris [AP-HP]), Paris, France
700    1_
$a Klingebiel, Thomas $u German Cancer Research Center (DKFZ), Heidelberg, Germany $u Department of Pediatrics, Universitätsklinikum Frankfurt, Frankfurt, Germany $u German Cancer Consortium (DKTK), Site Frankfurt, Frankfurt, Germany
700    1_
$a Micalizzi, Concetta $u Department of Pediatric Sciences, Istituto Giannina Gaslini, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Genoa, Italy
700    1_
$a Michel, Gérard $u Pediatrics and Pediatric Oncology, Hôpital de la Timone, Marseilles, France
700    1_
$a Nysom, Karsten $u Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark
700    1_
$a Rives, Susana $u Pediatric Hematology and Oncology, Institut de Recerca, Hospital Sant Joan de Deu de Barcelona, Barcelona, Spain
700    1_
$a Schmugge Liner, Markus $u Division of Haematology, Kinderspital Zürich, Zürich, Switzerland
700    1_
$a Zecca, Marco $u Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
700    1_
$a Schönung, Maximilian $u Translational Cancer Epigenomics Section, Division of Translational Medical Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany $u Faculty of Biosciences, Heidelberg University, Heidelberg, Germany
700    1_
$a Baumann, Irith $u Department of Pathology, Böblingen Hospital, Sindelfingen, Germany
700    1_
$a Nöllke, Peter $u Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, University of Freiburg, Freiburg, Germany
700    1_
$a Benettaib, Bouchra $u Formerly Bristol Myers Squibb, Princeton, NJ
700    1_
$a Biserna, Noha $u Formerly Bristol Myers Squibb, Princeton, NJ
700    1_
$a Poon, Jennifer $u Bristol Myers Squibb, Princeton, NJ
700    1_
$a Simcock, Mathew $u Celgene Corporation, a Bristol Myers Squibb company, Uxbridge, United Kingdom
700    1_
$a Patturajan, Meera $u Bristol Myers Squibb, Princeton, NJ
700    1_
$a Menezes, Daniel $u Bristol Myers Squibb, San Francisco, CA
700    1_
$a Gaudy, Allison $u Bristol Myers Squibb, Princeton, NJ
700    1_
$a van den Heuvel-Eibrink, Marry M $u Hematology-Oncology, Prinses Máxima Center for Pediatric Oncology/Hematology, Utrecht, The Netherlands
700    1_
$a Locatelli, Franco $u Department of Pediatric Hematology and Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy; and $u Department of Pediatrics, Sapienza University of Rome, Rome, Italy
773    0_
$w MED00194912 $t Blood advances $x 2473-9537 $g Roč. 5, č. 14 (2021), s. 2901-2908
856    41
$u https://pubmed.ncbi.nlm.nih.gov/34297046 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20211013 $b ABA008
991    __
$a 20211026133945 $b ABA008
999    __
$a ok $b bmc $g 1714379 $s 1145805
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2021 $b 5 $c 14 $d 2901-2908 $e 20210727 $i 2473-9537 $m Blood advances $n Blood Adv $x MED00194912
LZP    __
$a Pubmed-20211013

Find record

Citation metrics

Archiving options