Introduction

This family protocol summary provides a general overview of the Children’s Oncology Group (COG) study AAML1531. It tells who is eligible and gives basic information about the study. More details about the study are in the consent form. You can get this from your oncologist.

AAML1531 is a Phase III clinical trial. A trial is another word for a study. This study (clinical trial) is a therapeutic clinical trial. That means it is done to learn about treatment – its safety and how well it works. The purpose of a Phase III trial is to learn if a new treatment that is known to work in treating a type of cancer is better in some way than the standard treatment. For example, does it have better cure rates, longer control of disease, fewer or less serious side effects, or fewer days in the hospital?

AAML1531 aimed to compare two different treatments. These treatments are called study arms. On AAML 1531, these study arms aim to provide more personalized treatment for patients. One study arm reduced the intensity of chemotherapy for standard risk patients and is now closed to new patients. The other arm provides more intensive therapy than previous studies for high risk patients and is still open. It is not known if the new high risk treatment is better than the treatment used previously.

In most clinical trials, we will not know which treatment is better until all of the children taking part in the trial have completed treatment and have been followed for several years. If one of the treatments is found to be better or safer than the others while the trial is still going on, the trial will be stopped. All children still in the trial will be given the treatment with the best results whenever possible.

It is important to 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 health care team in any way. You can find additional information about participation in clinical trials at www.childrensoncologygroup.org Always discuss any questions that you may have with your health care team.

Study Number

AAML1531

Study Title

Risk-stratified Therapy for Acute Myeloid Leukemia in Down Syndrome

Study Opening Date

AAML1531 opened on November 23, 2015. The study was temporarily closed to new patients on October 1, 2018. When the study re-opens it will be only for patients on the high risk arm. It is expected that this study will remain open until November 2019.

General Patient Eligibility

• Age: 3 months - 4 years of age
• Diagnosis: Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)
• Down Syndrome (constitutional trisomy 21 or trisomy 21 mosaicism)

Please consult your doctor to determine whether you or your child may participate in this study.

General Background and Study Goal

AML in children with Down syndrome (ML-DS) is now recognized as a unique and distinct form of leukemia. Most children with ML-DS have a significantly higher cure rate and lower relapse rates than children with AML who do not have DS. However, children with DS may experience more side effects from chemotherapy than children without DS. A small proportion of children with DS AML have disease that may actually require more intensive therapy for cure.

In this study children will be assigned to a risk group based on their response to initial treatment. The term "risk" in risk group refers to the risk of the leukemia coming back (relapse). Knowing a patient’s risk group helps determine the intensity of treatment. This is determined by a laboratory measurement that is able to detect very small amounts of leukemia cells in the bone marrow after the first course of treatment. This laboratory test is called minimal residual disease or MRD.

Children will be classified after their first cycle of therapy as

• Standard risk - low MRD (less than 0.05%), or
• High risk – high MRD (greater than or equal to 0.05%)

The primary goals of this study are:

• For children with standard risk disease to determine if the drug treatment called "high dose cytarabine" (HD Ara-C) can be removed from treatment
• For high risk patients to determine if survival rates can be improved by intensifying treatment

Summary of the Treatment

All children will receive the same first course of treatment called induction I. This course includes the drugs standard-dose cytarabine, daunomycin and thioguanine.

At the end of induction I, a bone marrow aspiration will be done to determine the level of MRD. The strength of further treatment will be determined based on this result. It measures how well the leukemia cells are responding to chemotherapy.

Arm A: Standard Risk patients will not continue on this study and instead receive chemotherapy per their institution's standard of care based (best known treatment).

Arm B: High Risk patients will receive

• Induction II with HD Ara-C and mitoxantrone
• Intensification I with HD Ara-C and etoposide
• Intensification II with HD Ara-C and asparaginase

For high risk patients, that is those with a high level of MRD after the first course of treatment, the bone marrow test and MRD measurement will be repeated following the second course of treatment (Induction II).

All patients will have a lumbar puncture with chemotherapy done at the time of diagnosis to determine if leukemia cells are present in the central nervous system (called CNS leukemia). Patients who show leukemia cells present in their central nervous system will have an additional 4-6 lumbar punctures with chemotherapy to treat CNS leukemia.

Special Considerations

• Patients on Arm B will be required to stay in hospital after receiving chemotherapy until recovery of white blood cells due to risk of infection after chemotherapy.
• Your institution may recommend that child remain in the hospital until recovery of white blood cells regardless of treatment arm.

Risks and Side Effects

Chemotherapy can cause side effects during and after treatment. All patients will be closely monitored for possible side effects of the medicines. All risks and side effects will be explained by your treatment team during the consent process. They can answer questions that you may have about giving permission for your child to participate in this clinical trial or about other aspects of care. Please refer to the consent form for a detailed explanation of the side effects associated with the treatment on this study.

Contact Information

Your child’s oncologist and nurses are the best sources for further information.

Study Chairs

Johann Hitzler, MD
The Hospital for Sick Children
Toronto, Ontario

Jason Berman, MD
IWK Health Centre
Halifax, Nova Scotia

FAMILY PROTOCOL SUMMARY REVIEW/APPROVALS