Introduction

This family protocol summary provides a general overview of the Children’s Oncology Group (COG) study AHOD1221. It tells who is eligible and gives basic information about the study. More details about the study are in the consent form and protocol. You can get these from your oncologist.

AHOD1221 is a Phase I/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 new disease treatment, its safety, and how well it works.

The purpose of the Phase I part of the trial is to learn the best dose (called the Recommended Phase 2 Dose or RP2D) of a drug or a drug combination. The Phase I part of AHOD1221 study was completed on 12/18/14.

The purpose of a Phase II trial is to learn if the 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 I 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.

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:

AHOD1221

Official Title:

A Phase 1/2 Study of Brentuximab Vedotin In Combination With Gemcitabine For Pediatric And Young Adult Patients With Relapsed Or Refractory Hodgkin Lymphoma

Study Opening/Closing Date

AHOD1221 phase 1 opened on 1/14/2013 and closed on 1/9/15 after the accrual of 16 patients. The recommended phase 2 dose (RP2D) of brentuximab was determined. The phase 2 component of the study opened on 2/23/2015 and closed to accrual on 12/13/16 with a total of 46 patients.

General Patient Eligibility

• Age: 12 months to 30 years.
• Diagnosis: Patients with Hodgkin Lymphoma:
  • that has been resistant to therapy;
  • who have relapsed within 1 year of ending initial therapy, with or without disease in the bone marrow.

General Background and Study Goal

Hodgkin lymphoma (HL) therapy has been very successful for the majority of patients, but a small percentage of patients with Hodgkin lymphoma do not achieve remission with traditional, first line treatments, and up to 30% of patients with Hodgkin lymphoma may experience a recurrence of disease. For these patients, long-term disease-free survival remains relatively low.

Researchers want to improve the cure rate for relapsed and persistent HL. High dose chemotherapy with autologous stem cell rescue can significantly improve the survival for this group of patients, if they are in complete remission prior to beginning transplant. Those patients who still have disease present prior to transplant are at increased risk of relapse following transplant. Researchers hope that AHOD1221 treatment will result in complete remission for patients with persistent or relapsed HL.

AHOD1221 uses two drugs: gemcitabine and brentuximab vedotin. Brentuximab vedotin is a monoclonal antibody (brentuximab) linked to an anti-cancer drug (vedotin). The antibody is specific to a receptor called CD30, which is present on the surface of all Hodgkin lymphoma cells. After attaching to the cells, the vedotin enters the HL cells and kills them. Brentuximab vedotin has been studied in adults with HL with promising results, however, there have not been any pediatric specific trials. Gemcitabine has been used in pediatric HL studies, and is effective and well-tolerated. Brentuximab vedotin will be used with Gemcitabine in the hope of achieving a greater complete remission rate than there has been with past treatments.

Summary of the Treatment

Brentuximab vedotin will be given IV on day 1 and gemcitabine will be given IV on days 1 and 8, every 21 days. A cycle is 21 days in length.

Disease evaluation by PET scan, CT scan and breathing test will be performed after 2 cycles. Patients with disease in their bone marrow will also need a bone marrow test. If the disease has shown a total response after the first two cycles, patients may proceed to transplant. All other patients will receive two more cycles, followed by disease evaluation. Depending on the disease response and how the patient tolerates therapy, treatment may continue for up to 16 cycles.

Special Considerations

• Patients with shortness of breath while resting, or those who require oxygen, or who are unable to exercise without becoming overly out of breath are not eligible.
• Patients with Hodgkin lymphoma who were previously treated with radiation therapy ONLY are not eligible.
• Patients with Hodgkin lymphoma in the bone marrow will need repeated bone marrow biopsies performed until negative prior to stem cell collection.
• Long acting Neulasta cannot be used on this study; patients will require daily neupogen subcutaneous or intravenous injection daily starting on day 9 of each cycle.
• Blood will be drawn on day 1 of each cycle prior to Brentuximab infusion.

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

Peter Cole MD
The Children’s Hospital at Montefiore
111 E 210 St
Bronx, NY 10467

FAMILY PROTOCOL SUMMARY REVIEW/APPROVALS