COG AAML1031: A Phase III Randomized Trial for Patients with de novo AML Using Bortezomib and Sorafenib (IND# 114480; NSC#681239, NSC# 724772) for Patients with High Allelic Ratio FLT3/ITD


You are being asked to take part in this research study because you have been diagnosed with Acute Myeloid Leukemia (AML). 

AML is a cancer of the bone marrow, the spongy tissue inside the large bones of the body where blood cells are made. InAML, the bone marrow makes large numbers of immature white blood cells called blasts. These blast cells crowd out the normal cells of the bone marrow. They may also invade body organs including the brain, testes, ovaries, or skin. These cancerousAMLcells can sometimes form a solid tumor called a chloroma.

In the United States, nearly 500 children, adolescents and young adults are diagnosed with AML every year and half are cured with standard therapy. In other words, half of the children, adolescents and young adults diagnosed with AML remain with no signs of cancer (remission) for 5 years. The overall goal of this study is to see if we can increase this cure rate without causing more serious side effects of therapy. Side effects are unintended and unwanted results of treatment.

Researchers want to know if they can improve the cure rate for AML by adding an investigational drug, called bortezomib, to the standard cancer fighting drugs called chemotherapy. Bortezomib is an experimental drug that has been shown to reduce the numbers of leukemia cells, as well as increase the effect of chemotherapy. Bortezomib has been studied in adults with AML in combination with standard chemotherapy drugs. It has also been studied in small groups of pediatric patients. These studies have determined what dose of bortezomib can be tolerated when given with other chemotherapy drugs. In this study, researchers want to confirm that bortezomib is tolerated when given with standard chemotherapy treatment. They also want to see if bortezomib helps improve treatment success for children, adolescents and young adults with AML. Bortezomib is approved by the FDA for the treatment of certain types of cancer (specifically multiple myeloma and mantle cell lymphoma) in adults.

Researchers also want to find out the dose of a different investigational drug, called sorafenib, which has been shown to be tolerated when given in combination with standard chemotherapy treatment for adults with high-risk AML. These patients are at high risk because they have an abnormality in the structure of a gene called FLT3. Genes are materials passed down from birth parents to their child that determines the makeup of the body and mind. FLT3 plays an important role in the normal making of blood cells. It is called wild-type FLT3 when there is no abnormal change in its structure (i.e., there is no mutation in the gene). However, this gene can have permanent changes that cause it to function abnormally by making cancer cells grow and is called mutant FLT3. Patients with more mutant FLT3 than wild-type FLT3 in their cancer cells (i.e. high amounts of FLT3 gene mutation), are less likely to respond well to standard treatment.

Sorafenib has been shown to block the abnormal function of the FLT3 gene that makes cancer cells grow. Sorafenib has been studied in adults with AML in combination with standard chemotherapy drugs. These studies have found the dose that can safely be given to adults, and that sorafenib significantly increases the number of adults with high-risk AML who go into remission. Sorafenib has also been studied in small groups of pediatric patients. These studies have found the dose of sorafenib alone that can be given to children. One other study is trying to find the dose of sorafenib that can be combined with AML chemotherapy. The starting dose for the AAML1031 study is based on the early results from that study. Sorafenib is approved by the FDA for the treatment of certain types of cancer (specifically liver and kidney cancer) in adults.

Another goal of the study is to understand the biology of AML better. Study doctors want to test blood or bone marrow for certain genetic changes (called genetic markers) in leukemia cells. This would help them to learn more about AML and how to treat patients better. They also want to look for very small amounts of leukemia. This is called minimal residual disease (MRD). Researchers will be using MRD and some particular genetic markers to predict a subject’s risk of the leukemia coming back (relapse). A subject is a person who agrees to take part in a study.

In this study, we also want to learn more about how treatment for AML affects your quality of life and more about the stress experienced by parents whose children are undergoing treatment for AML. We will study quality of life and parental stress of subjects who receive a stem cell transplant as well as subjects who are treated with standard chemotherapy.

COH Protocol Number : 11184 Number : NCT01371981

Principal Investigator : Harned, Theresa M.D.

Sponsor : Children's Oncology Group (COG)


Eligible Ages : <=29;>=1

Gender : Either

Treatment Intent : Non-Adjuvant treatment

Prior Chemotherapy :

Brain Metastases :

Measurable Disease :