Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma
Condition: Hodgkin Lymphoma
MeSH terms: Lymphoma; Hodgkin Disease
Intervention: brentuximab vedotin; doxorubicin; vinblastine; dacarbazine; G-CSF; nivolumab
Intervention description: 1.2 mg/kg by IV infusion; 25 mg/m^2 by IV infusion; 6 mg/m^2 by IV infusion; 375 mg/m^2 by IV infusion; Granulocyte colony stimulating factor (G-CSF) primary prophylaxis administered 24-36 hours after each dose of A+AVD; 240 mg by IV infusion
Intervention MeSH terms: Doxorubicin; Nivolumab; Dacarbazine; Brentuximab Vedotin; Vinblastine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 255.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: Brentuximab vedotin; Doxorubicin; Vinblastine; Dacarbazine; Nivolumab; Seattle Genetics

Summary:

      This trial will study two treatment combinations for classical Hodgkin lymphoma (cHL). This
      trial will find out if these two treatment combinations work to treat cHL. It will also find
      out what side effects occur. A side effect is anything the drug does besides treating cancer.
      This study will have three parts (Parts A, B, and C).

      The drugs used in Part A are a combination of targeted anticancer drug (brentuximab vedotin)
      and three chemotherapy drugs (doxorubicin, vinblastine, and dacarbazine). These four drugs
      are called "A+AVD." Participants will be treated with granulocyte colony stimulating factor
      (G-CSF) following every dose of A+AVD for 6 cycles of treatment (12 doses).

      Part A will look at whether the A+AVD drug combination reduces the number of participants who
      experience the side effect of febrile neutropenia. Febrile neutropenia is a very low white
      blood cell count and a fever, which can be life threatening.

      Parts B and C will use drug combination of brentuximab vedotin, plus nivolumab, doxorubicin,
      and dacarbazine. These four drugs are called "AN+AD." Parts B and C will study how well the
      drugs work to treat cHL and what side effects they cause.
    

Eligibility criteria:

        Inclusion Criteria

          -  Treatment-naïve, classic Hodgkin lymphoma (cHL) participants

               -  Participants enrolling in Part A of the study must have Ann Arbor Stage III or IV
                  disease

               -  Participants enrolling in Part B of the study must have Ann Arbor Stage I or II
                  cH: with bulky mediastinal disease, or Stage III or IV

               -  Participants enrolling in Part C of the study must have Ann Arbor Stage I or II
                  cHL without bulky disease

          -  Histologically confirmed cHL according to the current World Health Organization (WHO)
             Classification

          -  Bidimensional measurable disease as documented by PET/CT or CT imaging

          -  Age 12 years or older in the United States. For regions outside of the US,
             participants must 18 years or older.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

        Exclusion Criteria

          -  Nodular lymphocyte predominant HL

          -  History of another malignancy within 3 years of the first dose of study drug or any
             evidence of residual disease from a previously diagnosed malignancy. Exceptions are
             malignancies with a negligible risk or metastasis or death. Participants with
             nonmelanoma skin cancer, localized prostate cancer, or carcinoma in situ of any type
             are not excluded if they have undergone complete resection

          -  Prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy
             within 4 weeks of the first study drug dose

          -  Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or
             any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint
             pathways

          -  Active cerebral/meningeal disease related to the underlying malignancy

          -  Any active Grade 3 or higher viral, bacterial, or fungal infection within two weeks of
             the first dose of study drug (Grade 3 defined by the National Cancer Institute's
             Common Terminology Criteria for Adverse Events, NCI CTCAE Version 4.03)

          -  Current therapy with other systemic anti-neoplastic or investigational agents

          -  Planned consolidative radiotherapy (Parts B and C only)

          -  Active interstitial lung disease that is symptomatic or may interfere with the
             detection or management of suspected drug-related pulmonary toxicity (Parts B and C
             only)

          -  Grade 3 or higher pulmonary disease unrelated to underlying malignancy

          -  Documented history of idiopathic interstitial pneumonia or diffusing capacity of the
             lung for carbon monoxide <50% predicted

          -  History of a cerebral vascular event within 6 months of first dose of study drug

          -  Child-Pugh B or C hepatic impairment

          -  Grade 2 or higher peripheral sensory or motor neuropathy

          -  Participants with acute or chronic graft-versus-host-disease (GvHD) or receiving
             immunosuppressive therapy as treatment or as prophylaxis against GvHD

          -  Previous treatment with brentuximab vedotin

          -  Participants who are pregnant or breastfeeding

          -  Other serious condition that would impair the participant's ability to receive or
             tolerate the planned treatment and follow-up