Introduction

This family protocol summary provides a general overview of the Children's Oncology Group (COG) study AHOD1331. It tells who is eligible and gives basic information about the study. More details about the study are found in the consent form. You can get this from your oncologist.

AHOD1331 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 more about how well treatments work and the side effects of the treatments. 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?

AHOD1331 compares 2 treatments. These treatments are called study arms. Usually, one study arm is the standard or the best proven current treatment. The other study arm has 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 makes sure 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

AHOD1331

Title

A Randomized Phase 3 Study of Brentuximab Vedotin (SGN-35, IND #117117) for Newly Diagnosed High-Risk Classical Hodgkin Lymphoma (cHL) in Children and Young Adults

Study Opening Date

AHOD1331 opened on 3/9/15. The AHOD1331 committee hopes to enroll approximately 600 patients. It is expected that this study will remain open for 4 years.

General Patient Eligibility

• Age: 2 - 21 years old
• Diagnosis:newly diagnosed, high risk, classical Hodgkin lymphoma

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

General Background and Study Goal

Hodgkin lymphoma (HL) therapy has been very successful for the majority of patients. Even in patients classified as having high risk disease, therapy has been effective in curing the disease. However, the high doses of chemotherapy and radiation therapy needed to cure HL can cause significant long term side effects.

Side effects are unintended, unwanted results of treatment that may be harmful. These side effects can result from the chemotherapy or from the radiation therapy used to treat HL. Researchers believe HL can be treated successfully with less intense treatment, resulting in fewer side effects later in life.

Brentuximab vedotin is an agent that has shown activity against HL in previous studies. Brentuximab vedotin is a monoclonal antibody (brentuximab) linked to an anti-cancer drug (vedotin). The antibody is specific to a receptor called CD30, which is present on the surface of all Hodgkin lymphoma cells. After attaching to the cells, the vedotin enters the HL cells and kills them. Brentuximab vedotin has been studied in adults with HL with promising results; however, there have not been any Phase III clinical trials in children with HL.

AHOD1331 will also study the effect of decreasing the radiation "port," which is the total area of the body exposed to radiation therapy.

Doctors hope to learn if the addition of Brentuximab vedotin and decreasing total radiation exposure will have fewer long term side effects of treatment while maintaining the high cure rate of high risk HL.

An additional goal of AHOD1331 is to study the quality of life of study participants, as well as the financial cost of care (in the USA only) of patients receiving each arm of therapy. This will be done by completing questionnaires throughout treatment.

Summary of the Treatment

Chemotherapy

At study entry, patients will be randomized to either:

• ABVE-PC (standard arm)
  • Chemotherapy - Doxorubicin (also known as Adriamycin), Bleomycin, Vincristine, Etoposide, Prednisone, C yclophosphamide.
• Bv-AVEPC (experimental arm)
  • Chemotherapy - same medicines as above, except:
    • Brentuximab vedotin (Bv)
    • Fewer doses of vincristine
    • No bleomycin

All patients will receive 5 cycles of chemotherapy. A cycle lasts 21 days.

Radiation Therapy

• Radiation therapy will be given to patients with sites of disease that do not show a rapid response after 2 cycles of chemotherapy and to all patients with bulky chest (mediastinal) disease areas.

Special Considerations

Patients who participate in the study may have some additional blood tests. This blood will be drawn at times when other routine blood work is being drawn.

Brentuximab vedotin will be provided free of charge and supplied by the National Cancer Institute (NCI).

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 Chair

Sharon Castellino, MD, MSc
Children's Healthcare of Atlanta

FAMILY PROTOCOL SUMMARY REVIEW/APPROVALS