FDA Approves Expanded Indication of Daunorubicin/Cytarabine to Include Children With AML

The FDA approved a revised label for daunorubicin/cytarabine to treat newly-diagnosed therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes (AML-MRC) in pediatric patients aged 1 and older.

The FDA approved a revised label for daunorubicin/cytarabine (Vyxeos) to now include the indication to treat newly-diagnosed therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes (AML-MRC) in pediatric patients aged 1 and older, according to Jazz Pharmaceuticals, the agent’s manufacturer.1

The FDA granted approval to the revised label of thee combination based on safety data from 2 single-arm trials AAML1421 and CPX-MA-1201 – as well as efficacy data from the CPX351-301 study in adults.2

"The expansion of the Vyxeos label to include children is a welcome and necessary advancement in support of some of our most vulnerable patients," said Edward Anders Kolb, MD, director of the Center for Cancer and Blood Disorders at Nemours/Alfred I. DuPont Hospital for Children and chair of myeloid disease committee at Children's Oncology Group, added in the release. "Jazz has been a wonderful partner in pediatric drug development and we are grateful for the continued work being done to provide safe and effective therapies for children."

The 2 trials that supported the revised label for safety and pharmacokinetics of the regimen in children and young adults enrolled patients with AML or relapsed/refractory hematologic malignancies.

The phase 1/2 AAML1421 study enrolled a total of 38 pediatric patients aged 1 to 21 years who had AML in first relapse, while the phase 1 CPX-MA-1201 study enrolled a total of 27 patients aged 1 to 19 years who had relapsed/refractory hematologic malignancies.

Data from both trials demonstrated no differences in the toxicity profile of the regimen – a liposomal combination of daunorubicin (an anthracycline topoisomerase inhibitor) and cytarabine (a nucleoside metabolic inhibitor) – with regard to age.

Furthermore, data from the CPX351-301 study, conducted in adult patients, provided efficacy evidence to support the decision.

In the phase 3 CPX351-301 study, the most common adverse events included bleeding events, fever, rash, swelling, nausea, sores in the mouth or throat, diarrhea, constipation, muscle pain, tiredness, stomach pain, difficulty breathing, headache, cough, decreased appetite, irregular heartbeat, pneumonia, blood infection, chills, sleep disorders, and vomiting.

"At Jazz Pharmaceuticals, we believe all patients living with complex conditions deserve solutions, and work diligently to expand the science behind our therapies to ensure the greatest number of patients can benefit from our medicines," said Robert Iannone, MD, MSCE, executive vice president, research and development and chief medical officer of Jazz Pharmaceuticals, stated in a press release. "While pediatric patients represent a relatively small percentage of total AML patients, there is a critical need for more effective therapies in this setting. With the expansion of the Vyxeos label to include the pediatric population, Jazz demonstrates our continued commitment to broadening our cancer research and focusing on the people for whom we can have the greatest impact."


1. Jazz Pharmaceuticals announces FDA approval of additional indication for Vyzeos (daunorubicin and cytarabine) for the treatment of secondary acute myeloid leukemia in pediatric patients. News release. Jazz Pharmaceuticals plc. March 30, 2021. Accessed March 30, 2021. https://prn.to/3cxMsIx

2. Cooper TM, Absalon MJ, Alonzo TA, et al. Phase I/II study of CPX-351 followed by fludarabine, cytarabine, and granulocyte-colony stimulating factor for children with relapsed acute myeloid leukemia: a report from the Children's Oncology Group. J Clin Oncol. 2020;38(19):2170-2177. doi:10.1200/JCO.19.03306.