Introduction

This family protocol summary is about the Children's Oncology Group study AALL1631. 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.

AALL1631 is a Phase 3 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 drug or 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?

AALL1631 compares several different treatments. These treatments are called study arms. Usually, one study arm is the standard or the best proven current treatment. The other study arms have some changes or additions. The new treatment is thought to be at least as good as the standard treatment. It is not known if the new treatment will be better than the standard treatment.

In a Phase III trial, each child is assigned to a study arm by a method called randomization. This is a process like flipping a coin that assures that each child has a fair and equal chance of being assigned to any of the study arms. This way the study arms can be compared fairly.

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 getting checked 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

AALL1631

Official Title

International Phase 3 Trial in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Ph+ ALL Testing Imatinib in Combination with Two Different Cytotoxic Chemotherapy Backbones

Trial Opening Date

This study opened for enrollment on July 28th, 2017. This study plans to enroll 595 patients.

General Patient Eligibility

• Age: 1-21 years
• Diagnosis: Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL)
• Patients must be enrolled on the COG ALL Classification Study (AALL08B1 or APEC14B1), or have a baseline diagnostic bone marrow sample available.

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

General Background and Study Goal

Ph+ ALL accounts for about 3-5% of pediatric ALL diagnoses. Studies have shown that most patients with Ph+ ALL can be effectively treated with a combination of chemotherapy and a type of drug called a tyrosine kinase inhibitor (TKI). In this study, the TKI drug is Imatinib.

All patients will receive the same initial treatment. Following that, treatment will be based on risk group assignment. Current risk group assignment includes the response to initial treatment, meaning, how many of the leukemia cells are destroyed.

The term 'risk' in 'risk group' means the 'risk of the leukemia cells coming back,' so knowing the patient's risk group helps determine what treatment is best. After initial treatment, Ph+ ALL patients will be assigned to one of two risk groups:

• Standard Risk (SR)
• High Risk (HR)

Treatment for SR patients will compare 2 different chemotherapy regimens both which include a TKI. The goal is to maintain or improve cure rates while reducing side effects.

Treatment for HR patients will include chemotherapy followed by Hematopoietic Stem Cell Transplant (HSCT) and ongoing treatment with a TKI. The goal is to understand the impact of TKI following transplant on cure rates and side effects.

Summary of the Treatment

Standard Risk (SR)
Patients will be assigned to 1 of 2 chemotherapy backbone treatment plans. The two chemotherapy backbone treatment plans differ in the number of cycles and the types of drugs that are given. Both treatment plans will administer a TKI (Imatinib) as a part of therapy. AALL1631 hopes to learn which chemotherapy regimen has the best outcome for patients with Ph+ ALL

• Arm A: a TKI (Imatinib) combined with the current standard chemotherapy backbone
• Arm B: a TKI (Imatinib) combined with a less intensive chemotherapy backbone typically used by COG to treat other ALL patients without the Philadelphia chromosome.

High Risk (HR)
For patients with HR Ph+ ALL, TKI drugs have been standardly given with chemotherapy before HSCT, but not always after HSCT. This study looks at how well a TKI (Imatinib) works when given to children and young adults with HR Ph+ ALL. The TKI will be given with combination chemotherapy prior to HSCT and alone after HSCT.

Special Considerations

Optional research study tests are available. The study doctors would like to learn more about how children and young adults being treated for Ph+ ALL take chemotherapeutic medications as recommended when outside of the hospital. We call this study "The Adherence Study". Participation in this portion of the study will involve special medication bottles, caps, blood samples and completion of surveys.

Risks and Side Effects

Chemotherapy and other drugs used to treat cancer 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 Chair

Dr. Lewis Silverman, MD
Dana-Farber Cancer Institute

FAMILY PROTOCOL SUMMARY REVIEW/APPROVALS