Introduction

This family protocol summary provides a general overview of the Children's Oncology Group (COG) study AALL1521. 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.

AALL1521 is a Phase II 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 II trial is to learn if a new treatment works in treating a specific type of cancer and how it affects the body.

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

AALL1521

Official Title

A Phase II Study of the JAK1/JAK2 Inhibitor Ruxolitinib with Chemotherapy in Children with De Novo High-Risk (HR) Cytokine Receptor-Like Factor 2-Rearranged (CRLF2-R) and/or Janus Kinase (JAK) Pathway-Mutant Acute Lymphoblastic Leukemia (ALL)

Trial Opening Date

AALL1521 opened on 3/03/2016. The study will enroll about 180 patients across the country. It is expected that this study will remain open until the treatment efficacy phase enrolls 42 patients in each of groups A & B. There is no set date for the study enrollment to end.

General Patient Eligibility

• Age: 1-21 years old
• Diagnosis: Newly diagnosed high-risk B-cell acute lymphoblastic leukemia (B-ALL) with specific genetic changes in the leukemia cells

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

General Background and Study Goal

Despite excellent cure rates in children with ALL, there are subsets of ALL that have poorer outcomes. One of these subsets is called 'Ph-like ALL.' Ph-like ALL is seen in about 15% of children with B-ALL and 30% of young adults with B-ALL.

Recent studies have shown that patients with Ph-like ALL have leukemia cells with specific changes in genes that make the leukemia less likely to respond to various chemotherapy drugs, or have a higher risk of the leukemia coming back during or after therapy, known as 'relapse'.

The need for more intensive treatment may be based upon the response to treatment, measured by minimal residual disease (MRD) in the bone marrow after the first month of therapy. MRD is a laboratory measurement that is able to detect very small amounts of leukemia cells in the blood or bone marrow, which helps the treatment team understand how well a patient is likely to do with their future treatment.

Research has shown that about 50-60% of Ph-like ALL patients have specific changes in genes on the leukemia cells that are sensitive to a medicine called ruxolitinib. These changes can involve CRLF2 gene (rearrangement, CRLF2-R) with or without JAK mutations or other changes in JAK2, EPOR, IL7R, or SH2B3 ("JAK pathway") genes. This study will assign a patient to receive the new added medication, ruxolitinib, to standard chemotherapy if these specific genetic changes are identified in the leukemia cells. Ruxolitinib is used as "targeted" therapy, which means it is used to attack leukemia cells with those specific genetic changes.

The goal of this study in the first part (pilot phase) is to determine safe dosing and any side effects a patient will experience when taking ruxolitinib along with standard chemotherapy. In the second part (efficacy phase), the study will look at the effectiveness of the drug and if survival can be improved by adding ruxolitinib to standard chemotherapy as compared to patients treated only with standard chemotherapy.

Summary of the Treatment

This study will assign patients to receive ruxolitinib if specific genetic changes in the leukemia cells are identified. The patients will be divided into 4 different groups based on the specific genetic change in leukemia cells and the amount of remaining leukemia cells (MRD) after one month of therapy.

The 4 groups on this study are:

• Group A: CRLF2-R with JAK mutation + positive MRD
• Group B: CRLF2-R without JAK mutation + positive MRD
• Group C: JAK mutation without CRLF2-R + positive MRD
• Group D: Any genetic changes in groups A, B, or C + negative MRD

Standard chemotherapy consists of 5 phases called consolidation, interim maintenance 1, delayed intensification, interim maintenance 2, and maintenance.

• Pilot phase: 36 patients will receive standard chemotherapy plus ruxolitinib by mouth two times a day. Different doses of ruxolitinib will be tested.
• Efficacy phase: Once a safe dose of ruxolitinib and chemotherapy is determined from the pilot phase, 42 patients each in groups A & B and approximately 25 patients each in groups C & D will receive standard chemotherapy plus ruxolitinib at the determined dose by mouth two times a day.

Special Considerations

• This study is available at limited institutions.
• Ruxolitinib is a pill that is available in 2 sizes (5 mg or 25 mg tablets).
• If a dose is late by more than 4 hours, the dose should be skipped.
• If vomiting occurs, do not give another dose.
• Tablets may be crushed and mixed in water, orange or apple juice, or applesauce.

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

Sarah K Tasian, MD
Children's Hospital of Philadelphia

FAMILY PROTOCOL SUMMARY REVIEW/APPROVALS