IRB Number:

06-009362

Trial Status:

Open for Enrollment

Phase: III

Why is this study being done?

Acute myeloid leukemia (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 flood the bloodstream and invade vital organs such as the brain, testes, ovaries, or skin. These cancerous AML cells can sometimes form a solid tumor called a chloroma.

The standard treatment for this disease is to use a combination of cancer-fighting drugs called chemotherapy. Chemotherapy destroys the leukemia cells in the blood and bone marrow. In the first phase, called Induction 1, the medical team tries to remove all visible signs of leukemia and allow normal blood cells to be restored. This is called remission. The next phase of treatment is called Induction 2. Induction 2 is another round of chemotherapy to kill the few remaining leukemia cells that may have survived Induction 1. In the next phase of treatment, called Intensification 1, more chemotherapy is used to kill any remaining blast cells. Then the medical team does a Stem Cell Transplantation (SCT) or gives additional high doses of chemotherapy to try to keep the leukemia from coming back.

Nearly 500 children are diagnosed with AML every year, and half are cured with standard therapy. In other words, half of the children diagnosed with AML and treated as described above remain with no signs of cancer (remission) for five years. The overall goal of this study is to see if the research staff 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 chemotherapy drug, called gemtuzumab, to the standard chemotherapy treatments.
Gemtuzumab 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 gemtuzumab can be given safely with other chemotherapy drugs.

Another goal of this study is to determine which children with AML need a stem cell transplant and which children do not. During intensification treatment, the study doctors will assign patients to either receive more chemotherapy, or a stem cell transplant. This is decided based on two factors: 1) the patient's risk of AML coming back, and 2) if they have a matched stem cell donor available.

The research staff will also be studying how well children with Down syndrome do on the standard therapy. Down syndrome patients may respond differently to chemotherapy drugs than patients without Down syndrome. This study will give study doctors information about how Down syndrome patients respond to standard therapy.

A secondary goal of the study is to understand the biology of AML better. These tests are optional and will be done only if the patient agrees. Study doctors want to test blood or bone marrow for certain genetic changes 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 want to find out if measuring MRD can be used in the future to decide how great the risk of relapse is for a person.

In summary, the goals of this study are:
1. To see if adding a new drug called gemtuzumab to the current standard AML treatment will improve the cure rate without causing more serious side effects
2. To compare the outcomes of children who have higher risk disease and receive a stem cell transplant to children who do not have higher risk disease
3. To evaluate how well children with Down syndrome (who are over four years old) do when they receive the standard chemotherapy without gemtuzumab
4. To understand the biology of AML better with the optional biology tests

Who is Eligible to Participate in the Study?

-Newly diagnosed with acute myeloid leukemia (AML).
-Age one month to under 30 years old
-Patients with Down syndrome older than or equal to age 4

*More specific, detailed eligibility and/ or exclusion criteria are associated with this trial.

What is Involved With this Study?

Subjects (people participating in the study) will receive one of two different treatment plans. The treatment plan they 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 a computer to make sure that there are about the same number of people on each treatment plan of the study.

In this study, randomization takes place at the beginning 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 gemtuzumab. Gemtuzumab has been given to children with AML before, but it has not yet been compared to the current therapy to see if it improves outcome.

Subjects with Down syndrome enrolled in this study will not be randomized, and will be assigned to Arm A, the standard therapy. Prior studies of children with Down syndrome and AML show that they are often more responsive to treatment but have more complications than children without Down syndrome. Therefore, there needs to be more experience gained in treating children with Down syndrome, thus they will not receive the additional experimental drug in this study.

Treatment Plan
The treatment plan involves cancer fighting medicine called chemotherapy. The treatment on this clinical trial takes about six to eight months. It is divided into five stages: Induction 1, Induction 2, Intensification 1, Intensification 2, and Intensification 3.

Instead of Intensification 2 and 3, patients may receive a stem cell transplant.

Chemotherapy will be given in the following stages:
- Induction 1: chemotherapy given for 10 days followed by three weeks of rest (28 days total)
- Induction 2: chemotherapy is given for eight days followed by three weeks of rest (28 days total)
- Intensification 1: chemotherapy is given over five days followed by three weeks of rest
(26 days total)

The study doctor will then decide if the patient gets a stem cell transplant or more chemotherapy.
This will be decided based on three factors:
1) How well the patient does with the first courses of therapy,
2) If the patient's cells have certain genetic markers, and
3) If there is an appropriate stem cell donor for the patient.
If patients are given more chemotherapy, they will then proceed to:
- Intensification 2: given over five days followed by three weeks of rest (28 days total)
- Intensification 3: high dose chemotherapy given for two days followed by five days of rest, and then two more days of chemotherapy

If patients are given a stem cell transplant, they will then proceed to 11 days of treatment to kill all of the bone marrow cells. The stem cell transplant will then replace these cells with stem cells from a matched donor. The matched family donor may be a family member or it may be an unrelated person.

If subjects are assigned to Experimental Arm B, gemtuzumab will be added to two stages of treatment therapy: Induction 1 and Intensification 2. However, if subjects are assigned to Standard Arm A, they will not receive gemtuzumab with any of the treatments.

Bone marrow tests are done at the end of Induction 1, Induction 2, Intensification 1 and at the end of treatment. Subjects will be assigned to a Low, Intermediate, or High risk group based on tests of bone marrow samples and how well subjects respond to treatment. If the subject is not responding to treatment, their doctor will remove the patient from the study and recommend a different treatment.

How long will the Study run?

Patients in this clinical trial are expected to receive treatment on this study for six to eight months. After treatment, they will have follow-up examinations. The research staff will continue to collect some medical information about how patients are doing for 10 years after the last patient starts the study.

The patient's doctor or the study doctor may decide to take someone off this study under the following circumstances:
- If he/she believes that it is in the person?s best interest
- If the patient's disease comes back during treatment
- If the patient experiences side effects from the treatment that are considered too severe
- If new information becomes available that shows that another treatment would be better for the person

Patients can stop participating at any time. However, if deciding to stop participating in the study, patients are encouraged to talk to the study doctor and their regular doctor first. The study doctor or regular doctor will be able to help the patient stop treatment in a way that is safe.

Sponsor(s): Children's Oncology Group (COG)

Study Activation/Registration Date: 03/12/2007

IRB Review and Approval Date: 02/27/2007

Study Type: Treatment

Projected Accrual: The plan is to have up to 1,000 patients participate from multiple medical centers.

Costs of Study:There may be standard patient care costs related to participating in a cancer research study.

Principal Investigator: Vilmarie Rodriguez, MD

Who can I Contact for Additional Information on this Trial?

Complete Request Form for Cancer Clinical Trial Information at Mayo Clinic or
For more information about this study or other clinical trial options, please contact our Mayo Clinic Cancer Center Clinical Trials Referral Office.

• Patients living within the United States, call 507-538-7623, or e-mail cancerclinicaltrials@mayo.edu


• Patients living outside the United States may call our International Office at 507-284-8884, or e-mail intl.mcr@mayo.edu.

What is/are the Locations of this Clinical Trial?

• Rochester, MN
• Scottsdale and Phoenix, AZ

Last updated: 05/08/2008