Introduction

This family protocol summary provides a general overview of the Children's Oncology Group (COG) study ANHL1522. 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.

ANHL1522 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 a 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.

In a Phase II trial, patients with a specific type of cancer receive a new treatment using a 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 II trials are offered to patients whose disease has not responded to standard types of treatments or to patients whose disease doesn't have a standard treatment.

If you consent to being a part of this study, your child will receive one of two different treatment arms. The treatment arm is decided by a process called randomization. Randomization means that the treatment is assigned based on chance. It is a lot like flipping a coin, except that it is done by computer. The randomization process is described in the COG Family Handbook for Children with Cancer.

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

ANHL1522

Official Title

A Pilot Study of Rituximab (RTX) and Third Party Latent Membrane Protein (LMP)-specific Cytotoxic T-Lymphocytes (LMP-TC, IND#17068) in Pediatric Solid Organ Recipients (SOT) with EBV-Positive CD20-Positive Post -Transplant Lymphoproliferative Disease (PTLD)

Study Opening Date

ANHL1522 opened on 3/6/2017. The ANHL1522 committee hopes to enroll 90 patients. It is expected that this study will remain open up to 5 years, anticipating an accrual rate of 19 patients per year.

General Patient Eligibility

• Age: Must be less than 30 years of age
• Diagnosis: Post-Transplant Lymphoproliferative Disease (PTLD)
• Other major enrollment criteria:
  • History of solid organ transplant
  • PTLD is positive for CD20 (a marker on the cells)
  • PTLD is able to be measured by CT scan
  • Patient does not have “fulminant PTLD”, a form of PTLD that can present with high fevers, low blood pressures and organs not functioning well
  • Patient does not have disease in brain/spinal cord
  • Patient did not respond to having anti-rejection medications decreased OR patient is unable to have anti-rejection medications decreased due to high risk of organ rejection

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

General Background and Study Goal

Post-Transplant Lymphoproliferative Disease (PTLD) can occur after a solid organ transplant. It may occur as a result of anti-rejection drugs and the Epstein Barr Virus (EBV). Anti-rejection medications, also called "immunosuppressive" medications, weaken the immune system so that it does not recognize an infection of the B cells (a type of white blood cell that makes antibodies) caused by EBV. As a result, the immune system cannot fight the virus.

Initial treatment is to reduce or stop the immunosuppressive medications.

For some children, immunosuppressive medications cannot be reduced because it increases the risk of rejection of their solid organ transplant or stopping the immunosuppressive medications only does not make the PTLD go away. These patients are treated with Rituximab (an antibody drug that can bind to and kill certain cancer cells), and sometimes, chemotherapy.

This study looks to improve outcomes of patients with PTLD, by treating them with special immune system cells called Latent Membrane Protein (LMP)-specific T cells (LMP-TC). These cells are trained to recognize proteins found on PTLD tumor cells if they are infected with EBV. The LMP-TC come from donors that are matched to the patient. It is expected that 8 to 9 out of 10 patients will have a matched donor available. This is the first investigational study that looks at how well this therapy works when given to children and adolescents with PTLD. This study will help determine if it is possible to give this treatment to pediatric patients.

The goal of this study is to improve the outcome of PTLD, without increasing the treatment related side effects. Additional goals of this study are to find out:

• How often Rituximab alone is effective in treating PTLD
• The good and/or bad effects for patients that get the LMP-TC treatment
• If measuring EBV levels in the blood can predict how well PTLD will respond to the treatments given in this study

Summary of the Treatment

In this study, all patients will receive the same first course of therapy, called "Induction." During Induction, each patient will receive Rituximab (RTX) once a week for 3 weeks. Induction lasts 21 days. At the end of Induction, an evaluation will be done to see if the tumor has changed. Based on the response to Induction therapy, patients will be assigned to one of two treatment arms. All patients will continue to have their disease evaluated after each course with imaging scans that will tell if they are responding to treatment.

If the evaluation shows the PTLD responded completely, the patients will be assigned to ARM RTX.
Treatment plan 1: Arm RTX. On this treatment arm, patients receive another 21 day course of Rituximab, like during Induction therapy.

If the evaluation shows the PTLD did not respond completely, patients will be assigned to Arm LMP-TC.
Treatment plan 2: Arm LMP-TC. On this treatment arm, patients will receive either one or two courses of LMP-TC, depending on response to treatment. The treated cells will be given on Day 0 and Day 7 of each course. Each course is 6 weeks in length.

Special Considerations

There will be extra blood tests taken at the same time as your regular blood tests. These tests are testing whether the EBV virus is still found in the blood. There are some other blood tests for research which are voluntary. These extra tests do not require extra needle sticks. There may be side effects with the experimental LMP-TC therapy which are described in the consent form. There may be other side effects that we do not know about yet. These may require you to visit your hospital or doctor more frequently.

Sexually active patients must agree to use effective contraception during the study.

Patients that are pregnant or breast-feeding are not eligible for this study.

Patients with certain infections are not eligible for this study.

Risks and Side Effects

Cancer therapy 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 you or 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. Birte Wistinghausen
Icahn School of Medicine at Mount Sinai

Dr. Catherine Bollard
Children's National Medical Center

FAMILY PROTOCOL SUMMARY REVIEW/APPROVALS