Introduction

This family protocol summary provides a general overview of the Children's Oncology Group (COG) study AAML1421. 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.

AAML1421 is a Phase 1/Phase 2 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 a new disease treatment, its safety, and how well it works.

The purpose of the Phase 1 part of the trial is to learn the best dose of a drug or a drug combination. The Phase I part of AAML1421 study was completed in December 2016.

The purpose of a Phase 2 trial is to learn if the treatment works in treating a specific type of cancer and how it affects the body. In a Phase 2 trial, patients with a specific type of cancer receive a new treatment using the dose that was found to be safe in a Phase 1 trial. Patients are checked for side effects of the treatment and to see whether the cancer shrinks or goes away. Phase 2 trials are offered to patients whose disease has not responded to standard types of treatments.

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

AAML1421

Title

A Phase 1/2 Study of CPX-351 Alone Followed by Fludarabine, Cytarabine, and G-CSF (FLAG) for Children with Relapsed Acute Myeloid Leukemia (AML); A Study of CPX-351 Alone Followed by Fludarabine, Cytarabine and G-CSF for Children with Acute Myeloid Leukemia (AML) That Has Come Back

Study Opening Date

AAML1421 opened on 04/25/2016. The AAML1421 committee hope to enroll 44 patients. It is expected that this study will remain open for 23 months.

General Patient Eligibility

• Age: 1 - 21 years of age
• Diagnosis: Refractory AML or 1st Relapse of Acute Myeloid Leukemia (AML)

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

General Background and Study Goal

AML is a type of cancer that occurs in the bone marrow, the spongy tissue inside the large bones of the body where blood cells are made. Most AML patients achieve a remission (an absence of signs and symptoms) after initial treatment. However, some patients have remaining leukemic cells in their marrow even after intensive treatment. This is referred to as "refractory leukemia.". In other patients, their AML comes back after treatment. This is called "relapsed leukemia."

Treatment for AML involves high doses of cytarabine and a common class of chemotherapy drugs called anthracyclines. High doses of anthracyclines are known to cause long-term side effects, especially to the heart. Study doctors are interested in finding a treatment for relapsed and refractory AML patients that decreases the likelihood of long-term side effects.

This study will test an experimental drug called CPX-351. CPX-351 is made up of two well-known anti-cancer drugs, 1) cytarabine and 2) an anthracycline called daunorubicin. What makes CPX unique is that the drug is contained within a capsule called a liposome. When these two drugs are contained inside a liposome, they stay in the bone marrow longer and may be more effective. Also, the liposomal formulation of the drug may be less likely to cause heart problems than traditional anthracycline drugs.

The main goals of this study are:

• To find out what effects, good and/or bad, the drug CPX-351, followed by a second cycle of cytarabine, fludarabine, and G-CSF, has on children and young adults with relapsed AML.
• To find out the whether CPX-351 followed by a second cycle of cytarabine, fludarabine and G-CSF is a beneficial treatment for relapsed AML in children and young adults.

In addition to the treatment goals, the study hopes to better understand how CPX-351 is distributed in the bodies of children and young adults whether or not the effects on the heart are decreased. You can choose to be in this clinical trial without taking part in the optional portion of the study.

Summary of the Treatment

Part 1 of the study treated patients with CPX-351 to determine the highest dose of CPX-351 that can be given without causing side effects that are too severe. Patients received 2 cycles of therapy that included CPX-351 in Cycle 1 and fludarabine/cytarabine in Cycle 2. Part 1 of the study has been completed as of 12/2016, and a recommended dose was identified for Part 2 of the trial.

Part 2 of the study will treat up to 38 patients to find out how effective the maximum tolerated dose of CPX-351 (determined in Part 1) is against relapsed and refractory AML. Patients will receive 2 cycles of therapy. Each cycle lasts approximately 4 weeks (28 days).

• Cycle 1: Intrathecal cytarabine (given in the spinal fluid) and CPX-351 (given on Days 1, 3 and 5). Cycle 1 is followed by an evaluation in which tests are done to see if the cancer has changed. If the cancer has not gotten worse and the CPX-351 does not cause bad side effects, patients will continue with Cycle 2.
• Cycle 2: fludarabine, cytarabine, and G-CSF. Bone marrow tests will be done at the end of cycle 2 to see how well patients respond to the treatment.

At the end of study treatment your doctor will discuss further treatment options with you. Further treatment may include some type of additional chemotherapy followed by a bone marrow (stem cell) transplant, if possible.

Special Considerations

• Patients with leukemia in the spinal fluid (CSF) or central nervous system (CNS) are not eligible for this study
• Patients taking medication to treat heart problem (left ventricular systolic dysfunction) are not eligible for this study

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. Todd Cooper, DO
Seattle Children's Hospital

FAMILY PROTOCOL SUMMARY REVIEW/APPROVALS