Introduction

This clinical trial summary is about the Children’s Oncology Group study ANBL1531. 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.

ANBL1531 is a Phase 3 clinical trial. A trial is another word for a study. This study (clinical trial) is a therapeutic clinical trial. The purpose of a Phase III trial is to learn if a drug or therapy known to work in treating a certain type of cancer is better than the standard treatment. For example: better cure rates, longer control of disease, fewer or less serious side effects, or fewer days in the hospital.

ANBL1531 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 3 trial, each child is assigned to a study arm by a method called randomization. This process is like flipping a coin to decide which study arm will be assigned to each child.

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 other(s) while the trial is still ongoing, the trial will be stopped. Then, all children receiving therapy will be given the treatment with the best known results.

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

ANBL1531

Study Title

A Phase 3 Study of 131I-Metaiodobenzylguanidine (131I-MIBG) or Crizotinib Added to Standard Thera[y for Children with Newly Diagnosed High-Risk Neuroblastoma

Study Opening Date

ANBL1531 opened on 5/9/18. The committee hopes to enroll 774 patients over a 5year period

General Patient Eligibility

• Age: Patients must be between the ages of 1 and 30 years of age.
• Diagnosis: newly diagnosed neuroblastoma with:
  • INRG Stage M with MYCN amplification or if > 547 days of age regardless of biological features
  • INRG Stages MS or L2 disease with MYCN amplification
  • Some patients who have progressed to stage M without therapy may also be eligible.

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

General Background and Study Goal

Neuroblastoma is the second most common malignant tumor of childhood. Standard therapy involves 3 components: Induction including Local Control, Consolidation and treatment of minimal residual disease with biologic agents. The main purposes of this research study are to find out if using additional therapies throughout therapy will increase the chance that the neuroblastoma will go away and then stay away. 131I-MIBG will be used in Induction for patients with high risk neuroblastoma. For patients that have a specific mutation in the ALK gene, crizotinib will be used throughout therapy.

Summary of the Treatment

In the Induction phase one of the additions to treatment is called MIBG therapy. An MIBG scan is a radiology scan to find other places in the body where neuroblastoma might be. 131I-MIBG is similar but “stronger” so it can find sites of neuroblastoma and also kill it. Since the 1980’s 131I-MIBG has been used for the treatment of patients whose neuroblastoma did not respond or came back so its use in up front therapy is promising. In this study it will be used as part of the Induction phase of therapy to those who are randomized to Arms B and C. MIBG is not available at all children’s cancer hospitals and so families may need to travel for this part of therapy.

Also in the Induction phase will be the addition of Crizotinib in some patients. Recent advances in cancer care have added medications that are known as “targeted agents.” Some children with neuroblastoma, about 14%, will have an abnormality of ALK gene which will hopefully respond to crizotinib; only those children with ALK abnormalities will be given crizotinib on Arm E.

The Consolidation phase includes a stem cell transplant for all children. Prior to transplant all children receive high dose chemotherapy. Children who are randomized to Arm C will receive two chemotherapy medications called busulfan and melphalan (BuMel). BuMel has been used in children with neuroblastoma in Europe and has been used in the Children’s Oncology Group along with our standard Induction therapy plan. Children who will get therapy on Arm C will have one transplant instead of two. This medication combination, BuMel, was well tolerated and we hope it may even be better than what we are currently using.

There are two parts to this study. Part one relates to the initial chemotherapy Induction phase of therapy and part two to randomized part of therapy. Treatment will start with 2 cycles of chemotherapy to begin to get rid of the neuroblastoma while additional tests on the tumor and scans are done, this is part one.

Once all the test results are back, you will be asked to participate in the second part of the clinical trial. This part of the study will separate patients by tumor testing and scan results into 5 different treatments, noted below.

Standard therapy, which is the best treatment we know so far, includes 5 cycles of chemotherapy, surgery, followed by 2 transplants, radiation and finally immunotherapy.

Arm A - this treatment is standard of care

Arm B - this treatment will include MIBG therapy in addition to standard therapy.

Arm C - those who are getting this therapy will get MIBG therapy and one transplant with the chemotherapies Busulfan and Melphalan.

Arm D - treatment for those whose tumor did not show up on the MIBG scan (also called MIBG non-avid) will get standard of care therapy.

Arm E - treatment for those whose tumor was shown to have the ALK abnormality. This arm will add the targeted agent crizotinib to standard care.

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

Dr. Steven G. DuBois, MD
Dana-Farber/Harvard Cancer Center

FAMILY PROTOCOL SUMMARY REVIEW/APPROVALS