Introduction

This family protocol summary provides a general overview of the Children's Oncology Group (COG) study AALL1331. 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.

AALL1331 is a Phase III 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 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?

AALL1331 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

AALL1331

Official Title

Risk-Stratified Randomized Phase III Testing of Blinatumomab in First Relapse of Childhood B-Lymphoblastic Leukemia (B-ALL)

Study Opening Date

AALL1331 opened on December 8, 2014. The AALL1331 committee hopes to enroll 598 patients. It is expected that this study will remain open through 2018.

General Patient Eligibility

• Age:1 - 30
• Diagnosis:First Relapse of B Lineage Acute Lymphoblastic Leukemia (B-ALL)

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

General Background and Study Goal

The majority of children diagnosed with ALL will be cured of their disease. However, patients who experience a relapse (meaning the disease has returned after a period of time when it was not detectable) have a lower chance of being cured, because relapsed leukemia is less likely to respond to chemotherapy. The best current treatment for children and adolescents with relapsed ALL is intensive chemotherapy and for many patients, a bone marrow transplant.

At the time of relapse, patients are assigned to a "risk group". The term 'risk' in 'risk group' means the 'risk of the leukemia cells coming back after treatment' so understanding the risk group helps determine what treatment is best. The risk group assignment is based on:

1. how soon after diagnosis and treatment the leukemia returns
2. where in the body the leukemia is found, and
3. how quickly the leukemia goes back into remission after starting this study treatment

Leukemia relapse can occur in the bone marrow, or in a site outside of the bone marrow (called extramedullary relapse), or both. Common sites of extramedullary disease include the central nervous system (brain and spinal cord, or CNS) and in males, the testicles.

MRD (minimal residual disease) is a laboratory measurement that is able to detect very small amounts of leukemia cells in the blood or bone marrow. The MRD level helps doctors know how quickly the leukemia cells are responding to treatment, and if the disease is still in remission.

Patients in this study are treated according to one of 4 risk groups:

Low Risk (LR)

• Current relapse in bone marrow occurred more than 36 months after first diagnosis AND no leukemia cells detected (this is called negative MRD) after first month of treatment, or
• Current relapse occurred outside of the bone marrow (called isolated extramedullary disease or IEM) more than 18 months after first diagnosis AND negative MRD after first month of treatment

Intermediate Risk (IR)

• Current relapse in bone marrow occurred more than 36 months after first diagnosis AND leukemia cells detected (this is called positive MRD) after first month of treatment, or
• Current relapse occurred outside of bone marrow more than 18 months after first diagnosis AND positive MRD after first month of treatment

High Risk (HR)

• Current relapse in the bone marrow occurred less than 36 months from first diagnosis, or
• Current relapse occurred outside of the bone marrow less than 18 months from first diagnosis

Treatment Failure (TF)

• Failure to respond to the first month of standard treatment on this protocol, or
• Failure to achieve remission following the second month of standard treatment on this protocol.

AALL1331 will determine if adding Blinatumomab to standard treatment can improve cure rates for children and adolescents with relapsed B lineage leukemia.

Blinatumomab is called a targeted therapy and is designed to recognize very specific cells within the body, called CD19 positive cells. CD19 is found on most B lineage leukemia cells. Blinatumomab links CD19 leukemia cells with the patient's own immune cells. When the patient's immune cells are linked to the leukemia cell by blinatumomab, the leukemia cells dies.

Summary of the Treatment

AALL1331 has 5 treatment arms:

There are 2 arms for treatment of patients in the Low Risk (LR) category. LR patients are randomized to receive:

• Arm C: Standard treatment, or
• Arm D: Standard treatment + 3 cycles of Blinatumomab given between cycles

There are 2 arms for treatment of patients in the Intermediate Risk (IR) and High Risk (HR) categories. Both IR and HR treatments include plans for bone marrow transplant. IR/HR patients are randomized to receive:

• Arm A: Two standard chemotherapy blocks followed by bone marrow transplant
• Arm B: Two cycles of Blinatumomab followed by bone marrow transplant

There is a 5th treatment arm for patients who did not achieve remission with standard treatment on this study, and thus have not received Blinatumomab:

• Salvage arm (Blinatumomab-S).
  • This arm includes Blinatumomab for up to 2 cycles followed by a decision to proceed to bone marrow transplant.

Special Considerations

• Blinatumomab is given continuous IV infusion for 28 days during each cycle.
• Patients receiving Blinatumomab will need a central venous line that has at least two lines (lumens).
• Patients receiving Blinatumomab will need to stay in the hospital for the first 2-3 days of each Blinatumomab cycle to be monitored for side effects.
  • The remainder of the 28 day cycle may be given at home via small portable pump.
  • Management of the home infusion will vary among hospitals.
• Patients receiving Blinatumomab will have additional blood samples required.
• Patients receiving Blinatumomab will be asked to provide optional blood samples that will also help to better understand how Blinatumomab works.

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

Patrick Brown, MD
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, MD.

FAMILY PROTOCOL SUMMARY REVIEW/APPROVALS