Introduction:

This family protocol summary is intended to provide an overview of the Children’s Oncology Group study AAML1031. It will provide information about the children that are eligible for this study and basic information regarding the study. The informed consent and protocol contain the full details of the study. Those documents are available to you from your oncologist.

This is a clinical trial specifically designed for children, adolescents and young adults who are newly 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. In AML, 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 cancerous AML cells can sometimes form a solid tumor called a chloroma.

Please understand that participating in a clinical trial is entirely voluntary. The decision about whether or not to participate will not affect the care provided by the healthcare team in any way. You can find additional information about participation on clinical trials at www.curesearch.org. Also, please discuss any questions that you have with your healthcare team.

Brief Title: COG AAML1031 for newly diagnosed Acute Myeloid Leukemia in Children, Adolescents and Young Adults, A Phase II/III Groupwide Study

Official Title: A Phase III Randomized Trial for Patients with de novo AML using Bortezomib (IND# 58443, NSC# 681239) and Sorafenib (BAY 43-9006, IND#69896, NSC# 724772) for Patients with High Allelic Ratio FLT3/ITD

Trial Opening Date: 6/20/2011. 1250 patients are expected to be enrolled over 4 years.

General Patient Eligibility:

  • Patient Age: Patients between 0 and 30 years of age eligible for this study.
  • For patients with: Newly diagnosed Acute Myeloid Leukemia that has not been treated with chemotherapy or radiation therapy
  • Patients with the following are not eligible for this study:
    • Down syndrome

General Background and Study Goal

Nearly 500 children 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 a new investigational drug, called bortezomib, to the standard cancer fighting drugs called 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.

Another goal of this study is to determine the safe dose of another drug called sorafenib with standard chemotherapy for patients who have high amounts of the FLT3 gene mutation. The study also will see if sorafenib with chemotherapy is effective treatment for patients with high-risk AML due to the FLT3 gene mutation in their leukemia cells. Sorafenib has been shown to block the abnormal function of the FLT3 gene that makes cancer cells grow. FLT3 is a gene that plays an important role in the normal process of making blood cells. The FLT3 gene is called wild-type FLT3 when there is no abnormal change (mutation) in the structure of the gene. The FLT3 gene is called mutant FLT3 when there is an abnormal change (mutation) in the structure of the gene. This abnormal change allows cancer cells to grow. 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 studied in adults with AML in combination with standard chemotherapy. These studies determined the dose of sorafenib that can safely be given to adults. In these studies, the addition of sorafenib to standard chemotherapy increased the number of adults with AML who went into remission. Sorafenib has also been studied in small groups of pediatric patients. These studies found the dose of sorafenib alone that can be given safely to children. The starting dose of sorafenib on this study is based on early results from a pediatric study that combined sorafenib with standard AML chemotherapy.

Another goal of the study is to understand the biology of AML better. These tests are optional and will be done only if you agree. The optional biology tests are explained in detail in the consent. Briefly, the study doctors want to test blood or bone marrow for certain genetic changes (called genetic markers) in leukemia cells. 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 relapse (the cancer comes back).

In this study the researchers also want to learn more about how treatment for AML affects the quality of life for patients. The researchers would also like to learn more about the stress experienced by parents whose children are undergoing treatment for AML.

In summary the main goals of this study are:

For subjects without high amounts of the FLT3 gene mutation,
1. To see if an investigational drug, called bortezomib, is tolerated when added to the standard AML treatment without causing too many serious side effects.
2. To compare the effects, good and/or bad, of adding bortezomib to the standard AML treatment to find out which is better.

For subjects with high amounts of the FLT3 gene mutation,
3. To determine the dose of sorafenib that can be safely given with the standard AML treatment.
4. To compare the effects, good and/or bad, of adding sorafenib to standard AML treatment to find out which is better.
5. To determine how effective the combination of sorafenib and chemotherapy will be at killing cancer cells.

Other goals are:
6. To study quality of life and parental stress of subjects who receive a stem cell transplant to subjects who are treated with chemotherapy.
7. To understand the biology of AML better with the optional biology tests.
8. To compare any changes in heart function with or without treatment with a drug called dexrazoxane. Dexrazoxane is a drug that is sometimes given to protect the heart. Your doctor will decide if you receive dexrazoxane.

Summary of the Treatment:

The treatment plan involves cancer fighting medicine called chemotherapy. The treatment on this clinical trial takes about 6 to 8 months. It is divided into 4 stages: Induction I, Induction II, Intensification I, and Intensification II. Depending on your disease risk group, you may receive a stem cell transplant instead of Intensification II. Details about the individual drugs and the treatment schedule are discussed in the informed consent document.

Subjects (people participating in the study) will get 1 of 3 treatment plans. The 3 treatment plans are called:

Arm A – Standard chemotherapy
Arm B – Standard chemotherapy plus bortezomib
Arm C – Standard chemotherapy plus sorafenib (only for subjects with high amounts of the FLT3 gene mutation).

Random Assignment to Arm A or Arm B

In this study, randomization takes place at the beginning of the study. The treatment plan subjects (people participating in the study) receive is decided by a process called randomization. Randomization means that the treatment is assigned based on chance. It is a lot like flipping a coin, except that it is done by computer to make sure that there are about the same number of people on each treatment plan of the study. Subjects will be assigned to either Arm A, the current standard therapy, or Arm B, which is considered the experimental arm. Arm B uses the current standard therapy in combination with bortezomib.

Assignment to Arm C

At the beginning of the study subjects will be tested for the FLT3 gene mutation. If the test results show high amounts of the FLT3 gene mutation, subjects will have the option to change treatment during Induction I and continue with standard chemotherapy plus sorafenib on treatment Arm C.

Risks and Side Effects

Chemotherapy can cause short- and long-term side effects. All patients will be closely monitored to reduce the likelihood of negative side effects. All risks and side effects will be explained in detail by your healthcare team during the consent process. They can answer any questions that you may have regarding participation on the clinical trial or other aspects of care. Please refer to the consent document for a detailed explanation of the side effects associated with the treatment on this study.

There is a risk of more side effects from the chemotherapy if you are treated with bortezomib or with sorafenib in addition to the usual chemotherapy.

Contact Information

Your child’s oncologist is the best source for further information. Physicians with eligible patients should refer questions to the principal investigator:

Principal Investigator

Richard Aplenc, MD, PhD
Children’s Hospital of Philadelphia
Pediatric Oncology/Stem Cell Transplant
4018 CTRB
3501 Civic Center Blvd
Philadelphia, PA 19104-4318
Phone: (267) 426-7252
Fax: (267) 425-0113
E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.