Purpose

This phase III trial studies brentuximab vedotin and combination chemotherapy to see how well they work compared to combination chemotherapy alone in treating children and young adults with stage IIB or stage IIIB-IVB Hodgkin lymphoma. Combinations of biological substances in brentuximab vedotin may be able to carry cancer-killing substances directly to Hodgkin lymphoma cells. Chemotherapy drugs, such as doxorubicin hydrochloride, bleomycin sulfate, vincristine sulfate, etoposide, prednisone, and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known if combination chemotherapy is more effective with or without brentuximab vedotin in treating Hodgkin lymphoma.

Category

IRB Number
20150884HU
NCT Number
NCT02166463
Open to Enrollment
Yes
Sponsor
National Cancer Institute (NCI) -



Study Contact

Principal Investigator
Anne-Marie Langevin

Virginia Diaz
(210) 562-9149
diazvr@uthscsa.edu



Eligibility

Eligible Ages
Between 2 Years and 22 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

    • Patients with newly diagnosed, pathologically confirmed cHL meeting one of the following Ann Arbor stages are eligible:

      • Stage IIB with bulk
      • Stage IIIB
      • Stage IVA

      • Stage IVB

        • If study eligibility by staging is uncertain, consultation with Imaging and Radiation Oncology Core (IROC) Rhode Island (RI) may be obtained prior to study enrollment

    • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (performed within 14 days prior to enrollment):

      • 2 to < 6 years: male 0.8 mg/dL, female 0.8 mg/dL
      • 6 to < 10 years: male 1 mg/dL, female 1 mg/dL
      • 10 to < 13 years: male 1.2 mg/dL, female 1.2 mg/dL
      • 13 to < 16 years: male 1.5 mg/dL, female 1.4 mg/dL
      • >= 16 years: male 1.7 mg/dL, female 1.4 mg/dL
    • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (performed within 14 days prior to enrollment)
    • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate transaminase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine transaminase [ALT]) < 2.5 x upper limit of normal (ULN) for age (performed within 14 days prior to enrollment)
    • Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by radionuclide angiogram
    • Forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) > 60% by pulmonary function test (PFT), unless due to large mediastinal mass from Hodgkin lymphoma (HL)
    • For children who are unable to cooperate for PFTs, the criteria are: no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry reading of > 92% on room air
    • All patients and/or their parents or legal guardians must sign a written informed consent
    • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria

    • Patients with nodular lymphocyte-predominant HL
    • Patients with an immunodeficiency that existed prior to diagnosis, such as primary immunodeficiency syndromes, organ transplant recipients and children on current systemic immunosuppressive agents are not eligible
    • Patients who are pregnant; (since fetal toxicities and teratogenic effects have been noted for several of the study drugs, a negative pregnancy test is required for female patients of childbearing potential)
    • Lactating females who plan to breastfeed
    • Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for 30 days after the last dose of chemotherapy
    • Patients known to be positive for human immunodeficiency virus (HIV) are not eligible
    • Patients who have received any previous chemotherapy or radiation therapy are not eligible
    • Patients who received systemic corticosteroids within 28 days of enrollment on this protocol, except as specified, are not eligible

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Single (Outcomes Assessor)
Condition
  • Ann Arbor Stage IIB Hodgkin Lymphoma
  • Ann Arbor Stage IIIB Hodgkin Lymphoma
  • Ann Arbor Stage IV Hodgkin Lymphoma
  • Ann Arbor Stage IVA Hodgkin Lymphoma
  • Ann Arbor Stage IVB Hodgkin Lymphoma
  • Childhood Hodgkin Lymphoma
  • Classic Hodgkin Lymphoma

    • Arm Groups

    ArmDescriptionIntervention
    Active Comparator

    Arm I (ABVE-PC)

    		Patients receive doxorubicin hydrochloride IV over 1-15 minutes on days 1-2, bleomycin sulfate IV over 10 minutes or SC on days 1 and 8, vincristine sulfate IV over 1 minute on days 1 and 8, etoposide IV over 60-120 minutes on days 1-3, prednisone PO BID or methylprednisolone IV on days 1-7, and cyclophosphamide IV over 30-60 minutes on days 1 and 2. Treatment repeats every 21 days for 5 cycles in the absence of disease progression or unacceptable toxicity.
  • Drug: Doxorubicin Hydrochloride

    Given IV

    Other names:

    • 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
    • ADM

    • Other: Laboratory Biomarker Analysis

      Correlative studies

    • Other: Pharmacological Study

      Correlative studies

    • Other: Quality-of-Life Assessment

      Ancillary studies

      Other names:

      • Quality of Life Assessment

    • Drug: Vincristine Sulfate

      Given IV

      Other names:

      • Kyocristine
      • Leurocristine Sulfate
      • Leurocristine, sulfate
      • Oncovin
      • Vincasar
      • Vincosid
      • Vincrex
      • Vincristine, sulfate

    • Biological: Bleomycin Sulfate

      Given IV or SC

      Other names:

      • Blanoxan
      • BleMomycine
      • Blenoxane
      • Bleo-cell
      • Bleo-S
      • Bleocin
      • Bleolem
      • Bleomycin Sulfas
      • Bleomycin Sulphate
      • Bleomycini Sulfas
      • Blexane
      • Oil Bleo

    • Drug: Cyclophosphamide

      Given IV

      Other names:

      • (-)-Cyclophosphamide
      • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
      • Carloxan
      • Ciclofosfamida
      • Ciclofosfamide
      • Cicloxal
      • Clafen <

    • Drug: Etoposide

      Given IV

      Other names:

      • Demethyl Epipodophyllotoxin Ethylidine Glucoside
      • EPEG
      • Lastet
      • Toposar
      • Vepesid
      • VP 16
      • VP 16-213
      • VP-16
      • VP-16-213
      • VP16

    • Drug: Methylprednisolone

      Given IV

      Other names:

      • Adlone
      • Caberdelta M
      • DepMedalone
      • Depo Moderin
      • Depo-Nisolone
      • Duralone
      • Emmetipi
      • Esametone
      • Firmacort
      • Medlone 21
      • Medrate
      • Medrol
      • Medrol Veride

    • Drug: Prednisone

      Given PO

      Other names:

      • .delta.1-Cortisone
      • 1, 2-Dehydrocortisone
      • Adasone
      • Cortancyl
      • Dacortin
      • DeCortin
      • Decortisyl
      • Decorton
      • Delta 1-Cortisone
      • Delta-Dome
      • Deltacortene
      • De

    • Other: Questionnaire Administration

      Ancillary studies

    • Experimental

    ARM II (Bv-AVEPC)

    		Patients receive brentuximab vedotin IV over 30 minutes on day 1. Patients also receive doxorubicin hydrochloride, etoposide, prednisone or methylprednisolone, and cyclophosphamide as in Arm I and vincristine sulfate IV over 1 minute on day 8. Treatment repeats every 21 days for 5 cycles in the absence of disease progression or unacceptable toxicity.
  • Drug: Brentuximab Vedotin

    Given IV

    Other names:

    • ADC SGN-35
    • Adcetris
    • Anti-CD30 Antibody-Drug Conjugate SGN-35
    • Anti-CD30 Monoclonal Antibody-MMAE SGN-35
    • Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35
    • cAC10-vc

  • Drug: Doxorubicin Hydrochloride

    Given IV

    Other names:

    • 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
    • ADM

    • Other: Laboratory Biomarker Analysis

      Correlative studies

    • Other: Pharmacological Study

      Correlative studies

    • Other: Quality-of-Life Assessment

      Ancillary studies

      Other names:

      • Quality of Life Assessment

    • Drug: Vincristine Sulfate

      Given IV

      Other names:

      • Kyocristine
      • Leurocristine Sulfate
      • Leurocristine, sulfate
      • Oncovin
      • Vincasar
      • Vincosid
      • Vincrex
      • Vincristine, sulfate

    • Drug: Cyclophosphamide

      Given IV

      Other names:

      • (-)-Cyclophosphamide
      • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
      • Carloxan
      • Ciclofosfamida
      • Ciclofosfamide
      • Cicloxal
      • Clafen <

    • Drug: Etoposide

      Given IV

      Other names:

      • Demethyl Epipodophyllotoxin Ethylidine Glucoside
      • EPEG
      • Lastet
      • Toposar
      • Vepesid
      • VP 16
      • VP 16-213
      • VP-16
      • VP-16-213
      • VP16

    • Drug: Methylprednisolone

      Given IV

      Other names:

      • Adlone
      • Caberdelta M
      • DepMedalone
      • Depo Moderin
      • Depo-Nisolone
      • Duralone
      • Emmetipi
      • Esametone
      • Firmacort
      • Medlone 21
      • Medrate
      • Medrol
      • Medrol Veride

    • Drug: Prednisone

      Given PO

      Other names:

      • .delta.1-Cortisone
      • 1, 2-Dehydrocortisone
      • Adasone
      • Cortancyl
      • Dacortin
      • DeCortin
      • Decortisyl
      • Decorton
      • Delta 1-Cortisone
      • Delta-Dome
      • Deltacortene
      • De

    • Other: Questionnaire Administration

      Ancillary studies

    •