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 compares 2 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 has reduced therapy for standard risk patients, while the other arm provides more intensive therapy for higher risk patients. It is not known if either of these treatments are better than the standard treatment.

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 when 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 team hopes to enroll 240 patients. It is expected that this study will remain open until November 2018.

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 (DS AML) is now recognized as a unique and distinct form of leukemia. Most children with DS AML have a significantly higher cure rate and lower relapse rates than children with AML without DS. However, children with DS may experience more side effects from chemotherapy than children without DS. Children with DS AML and MDS have an excellent prognosis and may therefore benefit from decreasing treatment intensity. Previous clinical trials have showed that decreasing the intensity of chemotherapy treatment for children with DS AML and MDS does not decrease cure rates. However, 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 means the chance of that the leukemia will relapse. Knowing a patient's risk group helps determine what treatment is best. This is determined by a laboratory measurement that is able to detect very small amounts of leukemia cells in the blood or bone marrow. 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:

  • To determine if the excellent survival rate can be maintained without using the drug treatment called “high dose cytarabine” (HD Ara-C) for children with standard risk disease
  • To determine if survival rates for high risk patients can be improved by intensifying therapy

Summary of the Treatment

All children will receive Induction I therapy. This includes the drugs: standard-dose cytarabine, daunomycin and thioguanine.

At the end of induction I therapy, a bone marrow aspiration and biopsy will be done to determine MRD. Further treatment will be determined by disease response.

Arm A: Standard Risk patients will receive

  • 2 additional cycles of chemotherapy with the same drugs as induction I called Induction II and III
  • 2 further cycles of chemotherapy with standard-dose cytarabine and etoposide called Intensification I and II

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

A bone marrow test with MRD will be repeated following Induction II for high risk patients.

All patients will have a lumbar puncture done at the time of diagnosis to determine if leukemia cells are present in the central nervous system (called CNS leukemia). No further lumbar punctures will be needed if leukemia cells are not present in the spinal fluid. Patients with leukemia cells present in the central nervous system will have 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 any questions that you may have about giving permission for your child to be in the clinical trial or 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  

Initial development Name Date
Written by Stephanie Cox, RN(EC), MN, NP-Pediatrics January 7, 2016
Reviewed/approved by (PI) Jason Berman, MD February 5, 2016
Ongoing review
Reviewed and updated by Stephanie Cox, RN(EC), MN, NP-Pediatrics March 6, 2017
January 31, 2018

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