HLHR13: Brentuximab Vedotin, Combination Chemotherapy, and Radiation Therapy in Treating Younger Patients with Stage IIB-IVB Hodgkin Lymphoma

Adcetris® (Brentuximab Vedotin) Substituting Vincristine in the OEPA/COPDac Regimen [Treatment Group 3 (TG3) of Euro-Net C1] With Involved Node Radiation Therapy for High-Risk Pediatric Hodgkin Lymphoma (HL)


Leukemia / Lymphoma

Phase I/II

Diseases Treated:

High-risk Hodgkin lymphoma

Eligibility Overview:

  • Has high-risk Hodgkin lymphoma
  • 18 years of age or younger
  • Has not received previous treatment for Hodgkin lymphoma
  1. Brief Summary

    This pilot phase 2 trial studies how well giving brentuximab vedotin, combination chemotherapy, and radiation therapy works in treating younger patients with stage IIB, IIIB or IV Hodgkin lymphoma.

    Monoclonal antibodies such as brentuximab vedotin:

    • Can block cancer growth in different ways
    • May block the ability of cancer to grow and spread
    • May find cancer cells and help kill them or carry cancer killing substances to them

    Chemotherapy such as etoposide, prednisone, doxorubicin hydrochloride, cyclophosphamide, and dacarbazine

    • Work in different ways to stop the growth of cancer cells, either by
      • Killing the cells
      • Stopping them from dividing

    Radiation therapy

    • Uses high-energy X-rays to kill cancer cells

    Giving brentuximab vedotin with combination chemotherapy may kill more cancer cells and reduce the need for radiation therapy.

    Primary Objectives

    • To evaluate the safety of brentuximab vedotin, etoposide, prednisone and doxorubicin hydrochloride (AEPA)/cyclophosphamide, brentuximab vedotin, prednisone and dacarbazine (CAPDac), as well as the efficacy (early complete response) after 2 cycles of AEPA chemotherapy in patients with high-risk Hodgkin lymphoma
    • To compare the event-free survival in patients with high-risk Hodgkin lymphoma treated with AEPA/CAPDac to the historical control unfavorable risk 2 arm (UR2) of the St. Jude HOD99 study

    Trial Outline

    AEPA regimen: Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients receive:

    • Brentuximab vedotin on Days 1, 8, and 15
    • Etoposide on Days 1 to 5
    • Prednisone 3 times daily (TID) on Days 1 to 15
    • Doxorubicin hydrochloride on Days 1 and 15

    CAPDac regimen: Treatment repeats every 21-28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients receive:

    • Cyclophosphamide on Days 1 and 8
    • Brentuximab vedotin on Days 1 and 8
    • Prednisone TID on Days 1 to 15
    • Dacarbazine on Days 1 to 3

    Beginning 2-3 weeks after CAPDac chemotherapy, patients with lymph nodes that do not go into remission after 2 courses of AEPA chemotherapy undergo radiation therapy daily, 5 days a week for 3-4 weeks.

    After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 2 years, every 6 months for 2 years, and then annually for 5 years.

    Study Arm

    Experimental: Treatment

    Participants receive AEPA regimen (brentuximab vedotin, etoposide, prednisone, doxorubicin), and CAPDac regimen (cyclophosphamide, brentuximab vedotin, prednisone, dacarbazine). Filgrastim may be given as clinically indicated. For those with lymph nodes that do not go into remission after 2 courses of AEPA chemotherapy, radiation therapy will be given. Some participants may volunteer to complete the quality of life assessment.

    Eligibility Criteria

    Inclusion Criteria:

    • Histologically confirmed, previously untreated CD30+ classical Hodgkin Lymphoma (HL). (Participants receiving limited emergent radiation therapy (RT) or steroid therapy - maximum of 7 days - because of cardiopulmonary decompensation or spinal cord compression will be eligible for protocol enrollment).
    • Age ≤ 18 years at the time of enrollment (i.e., participants are eligible until their 19th birthday).
    • Ann Arbor stage IIB, IIIB, IVA, or IVB.
    • Adequate renal function based on GFR ≥ 70 ml/min/1.73m^2 or serum creatinine adjusted for age and gender.
    • Adequate hepatic function (total bilirubin < 1.5 x ULN for age, and SGOT/SGPT < 2.5 x ULN for age).
    • Female participant who is post-menarchal must have a negative serum pregnancy test.
    • Female or male participant of reproductive potential must agree to use an effective contraceptive method throughout duration of study treatment.

    Exclusion Criteria:

    • CD30 negative HL.
    • Has received prior therapy for Hodgkin lymphoma, except as noted above.
    • Inadequate organ function as described above.
    • Inability or unwillingness of research participant or legal guardian / representative to give written informed consent.

    Study Design

    • Endpoint Classification: Safety/Efficacy Study
    • Intervention Model: Single Group Assignment
    • Masking: Open Label
    • Primary Purpose: Treatment
  2. About this clinical trial

    Hodgkin lymphoma is a cancer of the lymph system (a part of the body’s immune system). The lymph system is made up of tissue throughout the body that makes and stores infection-fighting cells.

    HLHR13 is a Phase II clinical trial for participants with high-risk Hodgkin lymphoma. The term “risk” refers to the burden (or amount) of disease the patient has and therefore the need to give more intense therapy upfront.

    Hodgkin lymphoma is one of the most treatable childhood cancers. Treatment for high-risk Hodgkin lymphoma usually includes intensive chemotherapy (treatment with anti-cancer drugs) and radiation therapy (the use of high-dose x-rays to kill cancer cells). While this treatment works well at curing the Hodgkin lymphoma, it can cause serious side effects later in life. These side effects can include problems with:

    • Growth
    • Fertility
    • Some organ functions
    • Development of another kind of cancer (called secondary cancer)

    Better treatments with fewer long-term side effects are needed, which is why St. Jude is offering this clinical trial. Researchers think that treating patients with high-risk Hodgkin lymphoma with "targeted" therapy may help patients to have fewer and/or less severe side effects later in life

    Purpose of this clinical trial

    In this clinical trial, St. Jude researchers want to find out if a new combination of drugs will be as effective and better tolerated compared to the standard chemotherapy treatment used for high-risk Hodgkin lymphoma. The main goal is to find out how many participants will go into complete remission (no signs or symptoms of Hodgkin lymphoma) after the first two cycles of chemotherapy.

    Several chemotherapy drugs commonly given together for Hodgkin lymphoma treatment will be used, except that a new drug called brentuximab vedotin will replace one of the usual chemotherapy drugs called vincristine. Brentuximab vedotin is made up of two parts:

    • A type of antibody (a man-made version of an immune system protein) that finds ("targets") and attaches to the surface of Hodgkin lymphoma cells, hence the term "targeted therapy."
    • A chemotherapy drug that stops the cancer cell from dividing, and kills the cancer cell.

    Brentuximab vedotin has been approved by the FDA for the treatment of adults with Hodgkin lymphoma, when other treatments have been tried and are no longer working. It has been shown to be well-tolerated without a lot of side effects in adults.


    There are three parts to this study:

    • Staging - The first step is to find out how much tumor there is and where it has spread.
    • Treatment – All study participants will receive chemotherapy. After the first two cycles of chemotherapy, your child will have tests to find out if there is any remaining Hodgkin lymphoma present.
      • If there are no signs of Hodgkin lymphoma, then your child will
        • Receive four more cycles of chemotherapy
        • Not have any radiation therapy
      • If Hodgkin lymphoma is still present, then your child will:
        • Receive four more cycles of chemotherapy
        • Receive limited radiation therapy  to kill any remaining lymphoma cells
    • Follow-up - After treatment ends, your child will be followed for at least 10 years to find out how well treatment worked to kill the cancer and keep it from coming back:
      • Year one: every three months
      • Years two and three: every four months
      • Years four and five: every six months
      • Years six to 10: once per year

    Eligibility overview

    • Has high-risk Hodgkin lymphoma
    • 18 years of age or younger
    • Has not received previous treatment for Hodgkin lymphoma
  3. HLHR13   Quick View
    Sponsor St. Jude Children's Research Hospital
    Collaborator Seattle Genetics, Inc
    Clinicaltrials.gov identifier NCT01920932
    Trial start date August 2013
    Estimated enrollment 77
    Study type Interventional
    Study phase Phase 2
    • Stage II Childhood Hodgkin Lymphoma
    • Stage III Childhood Hodgkin Lymphoma
    • Stage IV Childhood Hodgkin Lymphoma
    Ages Up to 18 years
    Principal investigator Monika Metzger, MD, MSc
    Study site St. Jude Children’s Research Hospital
    For a consultation or to discuss HLHR13 St. Jude Physician/Patient Referral Office


Monica Metzger, MD, MSc

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334

Referring or consulting clinicians only: protocolinfo@stjude.org
For all other inquiries about St. Jude Children's Research Hospital studies: referralinfo@stjude.org

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