AML23: Clinical Trial Studying the Safety of Using Venetoclax and Chemotherapy to Treat Newly Diagnosed Childhood AML

Venetoclax is an FDA-approved BCL2 inhibitor. The FDA approved the combination of venetoclax with low-dose therapy for the treatment of older adults with AML.

The St. Jude VENAML trial showed that venetoclax was safe and active when combined with intensive chemotherapy in pediatric patients with relapsed or refractory AML. The AML23 trial will test the safety and activity of venetoclax when added to standard chemotherapy in pediatric patients with newly diagnosed AML.

Venetoclax will be given with each course of therapy. Patients with low-risk AML will receive 4 courses of therapy, intermediate-risk patients will receive 5 courses of therapy, and high-risk patients will receive 2 or 3 courses of therapy followed by hematopoietic stem cell transplantation.

Primary Objectives

• Establish the safety of venetoclax added to standard chemotherapy in pediatric patients with AML
• Estimate the number of patients who become minimal residual disease (MRD) negative after one course of venetoclax-based induction therapy

Eligibility Criteria

Inclusion criteria include:

• Diagnosed with AML
• Older than 28 days and younger than 22 years
• No prior AML treatment
• Bilirubin ≤1.5 x institutional upper limit of normal

Exclusion criteria include:

• Treatment-related AML, Down syndrome, acute promyelocytic leukemia, chronic myeloid leukemia in blast crisis, juvenile myelomonocytic leukemia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or other bone marrow failure syndromes
• Uncontrolled systemic infection or other disease
• Prior exposure to anthracycline or anthracenedione
• Use of CYP3A inducers or inhibitors within 3 days of enrollment
• Pregnancy

Study Sites

St. Jude Children’s Research Hospital, Memphis, Tennessee
Collaborating sites in the U.S.

About this study

Acute myeloid leukemia (AML) is a kind of cancer that starts in the bone marrow. The bone marrow lies inside the large bones of the body and makes blood cells. Some of these cells can change and become abnormal, grow quickly, and crowd out the normal blood cells so they do not work as they should. AML treatment usually uses chemotherapy drugs to kill the leukemia cells.

In this study, scientists will add a drug called venetoclax to chemotherapy to treat newly diagnosed AML in children and young adults. Scientists hope that venetoclax will help improve the chances of long-term remission (no evidence of leukemia) in these patients. The U.S. Food and Drug Administration (FDA) has approved venetoclax to treat adults with AML. The drug has not yet been approved to treat AML in children.

A previous study found that venetoclax was safe and active when given to children who had AML that came back (relapsed) or resisted other treatments.

Purpose of this clinical trial

• Study the side effects of using venetoclax and chemotherapy to treat children with AML
• Learn more about how this treatment works

Eligibility overview

• Newly diagnosed with AML
• Older than 28 days and younger than 22 years
• No earlier treatment for AML
• Not pregnant
• Using birth control if capable of having children