Brentuximab Vedotin and Combination Chemotherapy in Treating Children and Young Adults With Stage IIB, Stage IIIB, IVA, or IVB Hodgkin Lymphoma
Condition: Ann Arbor Stage IIB Hodgkin Lymphoma; Ann Arbor Stage IIIB Hodgkin Lymphoma; Ann Arbor Stage IVA Hodgkin Lymphoma; Ann Arbor Stage IVB Hodgkin Lymphoma; Childhood Hodgkin Lymphoma; Classic Hodgkin Lymphoma
MeSH terms: Lymphoma; Hodgkin Disease
Intervention: Bleomycin Sulfate; Brentuximab Vedotin; Cyclophosphamide; Doxorubicin Hydrochloride; Etoposide; Laboratory Biomarker Analysis; Methylprednisolone; Pharmacological Study; Prednisone; Quality-of-Life Assessment; Questionnaire Administration; Vincristine Sulfate
Intervention description: Given IV or SC; Given IV; Given IV; Given IV; Given IV; Correlative studies; Given IV; Correlative studies; Given PO; Ancillary studies; Ancillary studies; Given IV
Intervention MeSH terms: Prednisone; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Cortisone; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Etoposide; Vincristine; Etoposide phosphate; Brentuximab Vedotin; Bleomycin; Podophyllotoxin; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Prednisolone hemisuccinate; Prednisolone phosphate; Immunoconjugates
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 600.0
Sex: All
Minimum age: 2 Years
Maximum age: 22 Years
Healthy volunteers: No

Summary:

      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 with bulk, stage IIIB, IVA, or 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 children with
      high-risk Hodgkin lymphoma.
    

Eligibility criteria:

        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