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Published results

VENAML: Chemotherapy Combined with Venetoclax in Children with Refractory or Relapsed Acute Myeloid Leukemia

Why was this study done?

Only 50–70% of children with newly diagnosed acute myeloid leukemia (AML) can be cured, and the outcomes for children with refractory (hard to treat) or relapsed (AML) are even lower. Survival after relapse is approximately 20–30%.

New therapies are needed.

The drug venetoclax is a promising therapy that has been approved by the FDA for treating adults with AML. In this two-part study, researchers studied whether the drug is safe and works well for children, adolescents and young adults. This study was done to find out the highest dose of venetoclax and standard chemotherapy (chemo) that did not cause severe side effects. Standard chemo was cytarabine with or without idarubicin.

The main goal of Part 1 of this study was to test the safety of low- and high-intensity venetoclax and chemo to find out the best doses to use in Phase 2 of the study. The main goal of Phase 2 was to determine the antileukemia effects of the recommended doses. The study looked at the rates of complete remission and complete remission with incomplete blood count recovery.

The study’s other goals were to:

  • Learn more about the side effects of venetoclax along with chemo
  • Find out how this drug affects the body’s cells
  • Learn how treatment with this drug affects the quality of life of patients

When was this study done?

Part 1 of this study opened in July 2017 and closed in July 2019. Part 2 closed in August 2020. 

What did the study consist of?

  • All patients had regular physical exams, tests and procedures.
  • Patients got venetoclax by mouth once a day in 28-day cycles. The drug was given at one of two dose levels (low-intensity or high-intensity) along with cytarabine, with or without idarubicin.
  • Patients who enrolled early in the study got lower doses of venetoclax and chemo than those who enrolled later. Patients got up to four cycles of therapy. 
  • Standard chemo drugs used to prevent or treat leukemia cells in the spinal fluid were also given into the spinal canal.
  • Clinicians collected blood and bone marrow samples for biomarker, genetic and pharmacokinetic studies. Surveys were used to collect data for quality-of-life studies.
  • The patient’s bone marrow was studied to find out how well the therapy worked.

What did we learn from this study?

We learned that venetoclax along with low- or high-intensity chemo is safe for children with high-risk AML. Of the 20 patients treated at the recommended Phase 2 doses, 70% showed complete response with or without complete blood count recovery (absence of leukemia cells in the bone marrow). Ten percent of the patients showed a partial response.

What are the next research steps as a result of this study?

Plans are underway for more studies on venetoclax along with high-intensity chemo in children with AML. Researchers want to find out the genetic subtypes of AML that could best respond to this new treatment. In this study, patients with FLT3 gene mutations did not respond to this drug. What we learn from genetic studies will help us tailor treatment to each patient.

How does this study affect my child?

Every survivor of AML should receive long-term follow-up care. Through the St. Jude After Completion of Therapy Clinic, your child will receive information and guidance for care after treatment. Please speak with your St. Jude doctor about specific guidelines that apply to your child.

For more information

Please talk with your child’s St. Jude doctor about questions or concerns you have as a result of this study.

Publication generated from this study:

Venetoclax in combination with cytarabine with or without idarubicin in children with relapsed or refractory acute myeloid leukaemia: a phase 1, dose-escalation study. Karol SE, Alexander TB, Budhraja A, Pounds SB, Canavera K, Wang L, Wolf J, Klco JM, Mead PE, Das Gupta S, Kim SY, Salem AH, Palenski T, Lacayo NJ, Pui CH, Opferman JT, Rubnitz JE. Lancet Oncol. 2020 Apr;21(4):551-560.

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.


Full title:

A Phase I and Expansion Cohort Study of Venetoclax in Combination with Chemotherapy in Pediatric Patients with Refractory or Relapsed Acute Myeloid Leukemia

Study goal:

To determine a tolerable combination of venetoclax plus chemotherapy in pediatric patients with relapsed or refractory AML


Acute myeloid leukemia (AML), acute undifferentiated leukemia, mixed phenotype acute leukemia


2 years to 21 years old

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