Introduction

This family protocol summary provides a general overview of the Children's Oncology Group (COG) study AALL15P1. 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.

AALL15P1 is a 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 clinical trial is to learn if a new treatment works in treating a specific type of cancer and how it affects the body.

In a clinical trial, patients with a specific type of cancer receive a new or different treatment than has been used in the past. Patients are checked for side effects of the treatment and to see whether the cancer shrinks or goes away.

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

AALL15P1

Official Title

A Groupwide Pilot Study to Test the Tolerability and Biologic Activity of the Addition of Azacitidine to Chemotherapy in Infants with Acute Lymphoblastic Leukemia (ALL) and KMT2A (MLL) Gene Rearrangement

Study Opening Date

AALL15P1 opened on 3/27/2017. The AALL15P1 committee expects to enroll at least 4 patients and at most 116 patients. It is expected that this study will remain open for 1.5 to 3 years.

General Patient Eligibility

• Age: Infants less than 1 year of age on the date of diagnosis (infants must also be more than 36 weeks gestational age at the time of enrollment)
• Diagnosis: Newly-diagnosed B lymphoblastic leukemia (B-ALL) or acute leukemia of ambiguous lineage (ALUL) with at least 50% B lymphoblasts.
  • All patients on the study will be treated with standard 5-week Induction course. After Induction, only subjects with KMT2A-rearrangement (KMT2A R) are eligible to continue on protocol therapy

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

General Background and Study Goal

About 75-80% of infants with leukemia have blasts (cancerous white blood cells) that contain a reordering of the genes within the DNA, called KMT2A gene rearrangement (KMT2A-R). This is a genetic finding unique to the leukemia cells. While most infants with KMT2A-R leukemia will go into remission, the leukemia often comes back, or relapses, and survival rates are low. It is believed that the KMT2A gene rearrangement causes the leukemic blasts to be resistant to chemotherapy through a process called hypermethylation. Hypermethylation occurs when an extra group of chemicals called a "methyl group" attaches to a DNA molecule.

In this study, a chemotherapy drug called azacitidine will be added to the standard chemotherapy regimen for infant leukemia. Azacitidine will be given as a "primer" prior to chemotherapy cycles to make the leukemia cells more sensitive to chemotherapy. This study will evaluate how well infants tolerate the addition of azacitidine to standard chemotherapy and will determine 5 year event free survival following this treatment.

This study will evaluate the biologic activity of azacitidine in each infant's blood cells. Also, minimal residual disease (MRD), which is a laboratory measurement that detects very small amounts of leukemia cells in the blood or bone marrow, will be measured and related to outcome. There are some optional studies investigating levels of azacitidine in the blood, T-lymphocyte stimulation, and how another chemotherapy agent, pegaspargase, is handled by the body. Your child's doctor will discuss all of these studies, including the optional studies, with you.

Summary of the Treatment

Leukemia treatment is divided into different phases of therapy. The standard treatment for infant leukemia currently includes these phases: Induction, Consolidation, Interim Maintenance, Delayed Intensification (divided into two parts), and Maintenance. This standard therapy has been shown, through previous clinical trials, to be the best therapy for infants with KMT2A-R leukemia at the present time. AALL15P1 treatment will add four 5-day courses of azacitidine, one course given prior to the chemotherapy phases of Consolidation, Interim Maintenance, and both parts of Delayed Intensification. The Maintenance phase does not include any azacitidine and is identical to standard therapy. All infants with KMT2A-R leukemia will receive four courses of azacitidine if enrolled on this clinical trial, unless complications or side effects prevent it from being given or continued.

Special Considerations

• Standard chemotherapy for infant leukemia is very intensive, and the risks and complications are well known. The chance of infection is quite high during the initial phases of treatment. There are specific recommendations regarding nutrition, skin care, and prolonged hospitalization with preventive use of antibiotics and antifungals.
• It is unknown if the addition of azacitidine will worsen the complications for infants during treatment. Standard recommendations will be encouraged for infants enrolled on AALL15P1.
• There will be additional visits for daily azacitidine infusions, and more blood tests will be drawn to study the biologic activity of azacitidine.
• There are additional bone marrow studies required at the end of consolidation and interim maintenance that may not be always be done with standard treatment.
• Azacitidine will be provided as an investigational drug and the commercial drug may not be used.
• Certain medications cannot be taken while on this study. Please consult with your medical team.

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

Erin Guest, MD
Children's Mercy Hospital
Kansas City, MO

FAMILY PROTOCOL SUMMARY REVIEW/APPROVALS