All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit Know AML.

  TRANSLATE

The aml Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the aml Hub cannot guarantee the accuracy of translated content. The aml and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.

The AML Hub is an independent medical education platform, sponsored by Astellas, Daiichi Sankyo, Johnson & Johnson, Kura Oncology and Syndax, and has been supported through educational grants from Bristol Myers Squibb and the Hippocrate Conference Institute, an association of the Servier Group. The funders are allowed no direct influence on our content. The levels of sponsorship listed are reflective of the amount of funding given. View funders.

Now you can support HCPs in making informed decisions for their patients

Your contribution helps us continuously deliver expertly curated content to HCPs worldwide. You will also have the opportunity to make a content suggestion for consideration and receive updates on the impact contributions are making to our content.

Find out more

Phase I study evaluating a KMT2A partial tandem duplication targeted regimen in R/R AML

By Anna Bartus

Share:

Apr 25, 2018


Acute myeloid leukemia (AML) patients with lysine methyltransferase 2A (KMT2A) partial tandem duplication (PTD) have poor outcomes.1  Alice S. Mims from the Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA, and colleagues previously showed that KMT2A wild type (WT) allele is epigenetically silenced in KMT2A PTD AML patients, moreover, allele re-expression of KMT2A can be augmented with DNA methyltransferase (DNMT) and HDAC inhibitors.

With the aim of developing a therapy regimen for KMT2A PTD AML patients, the study group conducted a phase I trial (NCT01130506) evaluating the combination of decitabine and vorinostat prior to high dose cytarabine in relapsed and refractory (R/R) AML patients. The results of the study were published ahead of print in Haematologica.2

Overall, 17 adult R/R AML patients were enrolled (median age = 46 years, 21–59) and four of them had KMT2A PTD. Patients were administered decitabine (20 mg/m2/day IV) on Days 1–10, vorinostat (400 mg/day orally) on Days 5–10, and cytarabine which was dose escalated (dose level 1: 1.5 g/m2/q12hr; dose level 2: 2 g/m2/q12hr; dose level 3: 2.5 g/m2/q12hr; and dose level 4: 3g/m2/q12hr IV) and was given twice a day on Days 12, 14, and 16.

Key findings:

Safety

  • At dose level 1, DLTs of prolonged mylosuppression occurred in two patients
  • Most common side effects included diarrhoea (41%), nausea (29%), fatigue (29%), febrile neutropenia (35%), and elevated alanine aminotransferase (35%)
  • Most common grade >3 toxicities were febrile neutropenia (35%) and catheter-related infections (24%)

Efficacy

  • Complete remission (CR) rate: 35% (6/17)
  • Two of the four patients harboring KMT2A PTD mutations achieved cytogenetic CR

In conclusion, decitabine, vorinostat prior to high-dose cytarabine regimen was well tolerated in R/R AML patients with KMT2A PTD and should be further investigated in a phase II setting.

The authors added that “the small number of patients limits the interpretation of these findings” and that “the study provides a framework for larger efficacy studies for AML patients with the uncommon but biologically distinct molecular feature of KMT2A PTD.”

References