TY - JOUR
T1 - A phase I/II trial of MEC (mitoxantrone, etoposide, cytarabine) in combination with ixazomib for relapsed refractory acute myeloid leukemia
AU - Advani, Anjali S.
AU - Cooper, Brenda
AU - Visconte, Valeria
AU - Elson, Paul
AU - Chan, Ricky
AU - Carew, Jennifer
AU - Wei, Wei
AU - Mukherjee, Sudipto
AU - Gerds, Aaron
AU - Carraway, Hetty
AU - Nazha, Aziz
AU - Hamilton, Betty
AU - Sobecks, Ronald
AU - Caimi, Paolo
AU - Tomlinson, Benjamin
AU - Malek, Ehsan
AU - Little, Jane
AU - Miron, Alexander
AU - Pink, John
AU - Maciejewski, Jaroslaw
AU - Unger, Allison
AU - Kalaycio, Matt
AU - de Lima, Marcos
AU - Sekeres, Mikkael A.
N1 - Funding Information:
A. Advani reports receiving commercial research grants from Takeda. A. Gerds is a consultant/advisory board member for Incyte, CTI Biopharma, Celgene, and Apexx Oncology. H. Carraway reports receiving speakers bureau honoraria from Celgene, Agios, Jazz, and Novartis, and is a consultant/advisory board member for Celgene, Agios, and Novartis. A. Nazha reports receiving commercial research grants from Jazz Pharma; reports receiving speakers bureau honoraria from Incyte, Novartis, Karyopharma, and Tolero; and is a consultant/ advisory board member for MEI. M. De Lima reports receiving commercial research grants from Celgene. M. A. Sekeres is a consultant/advisory board member for Celgene, Syros, and Millenium. No potential conflicts of interest were disclosed by the other authors.
Funding Information:
This trial was funded by Takeda/Millennium, and ixazomib was also provided by Takeda/Millennium for this trial. The Case Comprehensive Cancer also provided partial support for correlative studies through an EPCRS grant, the Translational Research Shared Resource of the Case Comprehensive Cancer Center (P30 CA043703), and the Genomics Core Facility of the CWRU School of Medicine's Genetics and Genome Sciences Department. We thank all patients for their willingness to participate in this trial. In addition, we thank our protocol and data coordinators (Jaime Fensterl, Allison Unger, Christopher Goebel); research nurses (Mary Lynn Rush, Samjhana Bogati, Eric Parsons, Rachael Diligente, Donna Kane); and laboratory/translational personnel (Nita Hoxha, Alek Nielsen, Cassandra Hirsch, and Simone Edelheit) for their enormous contributions to this trial.
Publisher Copyright:
2019 American Association for Cancer Research.
PY - 2019
Y1 - 2019
N2 - Purpose: The prognosis of patients with relapsed/refractory thrombocytopenia. Despite a poor risk population, the (R/R) acute myeloid leukemia (AML) remains poor, and novel response rate [complete remission (CR)/CR with incomplete therapies are needed. The proteasome pathway represents a count recovery (CRi)] was encouraging at 53%. Gene-potential therapeutic target. A phase I trial of the second-expression analysis identified two genes, IFI30 (g-interferon generation proteasome inhibitor ixazomib in combination inducible lysosomal thiol reductase) and RORa (retinoic with MEC (mitoxantrone, etoposide, and cytarabine) was orphan receptor A), which were significantly differentially conducted in patients with R/R AML. expressed between responding and resistant patients and Patients and Methods: Dose escalation of ixazomib was could classify CR. performed using a standard 3 3 design. Gene-expression Conclusions: These results are encouraging, but a random-profiling was performed on pretreatment and posttreatment ized trial is needed to address whether the addition of ixazo-bone marrow or blood samples. mib to MEC improves outcome. Gene-expression profiling Results: The maximum tolerated dose of ixazomib in com-also helped us identify predictors of response and potentially bination with MEC was 1.0 mg. The dose limiting toxicity was novel therapeutic targets.
AB - Purpose: The prognosis of patients with relapsed/refractory thrombocytopenia. Despite a poor risk population, the (R/R) acute myeloid leukemia (AML) remains poor, and novel response rate [complete remission (CR)/CR with incomplete therapies are needed. The proteasome pathway represents a count recovery (CRi)] was encouraging at 53%. Gene-potential therapeutic target. A phase I trial of the second-expression analysis identified two genes, IFI30 (g-interferon generation proteasome inhibitor ixazomib in combination inducible lysosomal thiol reductase) and RORa (retinoic with MEC (mitoxantrone, etoposide, and cytarabine) was orphan receptor A), which were significantly differentially conducted in patients with R/R AML. expressed between responding and resistant patients and Patients and Methods: Dose escalation of ixazomib was could classify CR. performed using a standard 3 3 design. Gene-expression Conclusions: These results are encouraging, but a random-profiling was performed on pretreatment and posttreatment ized trial is needed to address whether the addition of ixazo-bone marrow or blood samples. mib to MEC improves outcome. Gene-expression profiling Results: The maximum tolerated dose of ixazomib in com-also helped us identify predictors of response and potentially bination with MEC was 1.0 mg. The dose limiting toxicity was novel therapeutic targets.
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U2 - 10.1158/1078-0432.CCR-18-3886
DO - 10.1158/1078-0432.CCR-18-3886
M3 - Article
C2 - 30992301
AN - SCOPUS:85069051815
SN - 1078-0432
VL - 25
SP - 4231
EP - 4237
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 14
ER -