Clinical Trials /

Adcetris (Brentuximab Vedotin), Combination Chemotherapy, and Radiation Therapy in Treating Younger Patients With Stage IIB, IIIB and IV Hodgkin Lymphoma

NCT01920932

Description:

This pilot phase II 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. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer killing substances to them. Drugs used in 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 or by 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.

Related Conditions:
  • Hodgkin Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Adcetris</span> (<span class="go-doc-concept go-doc-intervention">Brentuximab Vedotin</span>), <span class="go-doc-concept go-doc-intervention">Combination Chemotherapy</span>, and <span class="go-doc-concept go-doc-intervention">Radiation</span> Therapy in Treating Younger Patients With Stage IIB, IIIB and IV <span class="go-doc-concept go-doc-disease">Hodgkin Lymphoma</span>

Title

  • Brief Title: Adcetris (Brentuximab Vedotin), Combination Chemotherapy, and Radiation Therapy in Treating Younger Patients With Stage IIB, IIIB and IV Hodgkin Lymphoma
  • Official Title: Adcetris Substituting Vincristine in the OEPA/COPDac Regimen [Treatment Group 3 (TG3) of Euro-Net C1] With Low Dose Tailored-Field Radiation Therapy for Unfavorable Risk Pediatric Hodgkin Lymphoma
  • Clinical Trial IDs

    NCT ID: NCT01920932

    ORG ID: HLHR13

    NCI ID: NCI-2013-01123

    Trial Conditions

    Stage II Childhood Hodgkin Lymphoma

    Stage III Childhood Hodgkin Lymphoma

    Stage IV Childhood Hodgkin Lymphoma

    Trial Interventions

    Drug Synonyms Arms
    brentuximab vedotin SGN-35, Adcetris(R) Treatment
    etoposide VP-16, Vepesid(R) Treatment
    prednisone prednisolone Treatment
    doxorubicin Adriamycin(R) Treatment
    cyclophosphamide Cytoxan(R) Treatment
    Dacarbazine(R) Dimethyl Triazeno Imidazole Carboximide (DTIC) Treatment
    filgrastim Neupogen(R) Treatment

    Trial Purpose

    This pilot phase II 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. Some block the ability of cancer to grow and spread. Others find
    cancer cells and help kill them or carry cancer killing substances to them. Drugs used in
    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 or by 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.

    Detailed Description

    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 high risk patients with Hodgkin lymphoma (HL).

    - To compare the event-free survival in high risk HL patients treated with AEPA/CAPDac to
    the historical control unfavorable risk 2 arm (UR2) of the St. Jude HOD99 study.

    SECONDARY OBJECTIVES:

    - To estimate the number of patients with adequate response according to the definitions
    in the Euro-Net C1 after 2 cycles of AEPA.

    - To evaluate the safety of Adcetris (brentuximab vedotin) in the AEPA/CAPDac regimen in
    children with high risk HL.

    - To describe acute hematologic, neuropathic, and infectious toxicities as they relate to
    transfusion requirements, growth factor support, episodes of febrile neutropenia and
    hospitalizations, according to the National Cancer Institute (NCI) Common Terminology
    Criteria for Adverse Events (CTCAE), version 4.0.

    - To study the association between local failure and original lymph node region and
    volume of radiation (patterns of treatment failure).

    - To assess patient-reported symptoms and health-related quality of life in children with
    high risk HL compared to those treated on the unfavorable treatment arm of the St. Jude
    HOD99 study.

    OUTLINE:

    AEPA REGIMEN: Patients receive brentuximab vedotin on days 1, 8, and 15, etoposide on days 1
    to 5, prednisone three times daily (TID) on days 1 to 15, and doxorubicin hydrochloride on
    days 1 and 15. Treatment repeats every 28 days for 2 courses in the absence of disease
    progression or unacceptable toxicity.

    CAPDac REGIMEN: Patients receive cyclophosphamide on days 1 and 8, brentuximab vedotin days
    1 and 8, prednisone TID on days 1 to 15, and dacarbazine on days 1 to 3. Treatment repeats
    every 21-28 days for 4 courses in the absence of disease progression or unacceptable
    toxicity.

    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.

    Trial Arms

    Name Type Description Interventions
    Treatment Experimental 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. brentuximab vedotin, etoposide, prednisone, doxorubicin, cyclophosphamide, Dacarbazine(R), filgrastim

    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.

    Minimum Eligible Age: N/A

    Maximum Eligible Age: 18 Years

    Eligible Gender: Both

    Primary Outcome Measures

    Response rate with PET and CT

    Event-free survival

    Secondary Outcome Measures

    Response rate

    Number of adverse events

    Local failure rate

    Patient quality of life (QoL)

    Parent proxy quality of life (QoL)

    Correlation of agreement between patient QoL and parent proxy QoL at multiple time points

    Correlation of agreement between patient QoL and symptom distress to patients treated on HOD 99 unfavorable at multiple time points

    Trial Keywords

    Pediatric cancer

    Hodgkin lymphoma

    Targeted therapy

    Frontline therapy

    Brentuximab vedotin

    Quality of Life

    OEPA/COPDac