Brentuximab Vedotin and Gemcitabine Hydrochloride in Treating Younger Patients With Relapsed or Refractory Hodgkin Lymphoma
Condition: Recurrent Adult Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Refractory Childhood Hodgkin Lymphoma
MeSH terms: Lymphoma; Hodgkin Disease; Recurrence
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This phase I/II trial studies the side effects and the best dose of brentuximab vedotin when
      given together with gemcitabine hydrochloride and to see how well they work in treating
      younger patients with Hodgkin lymphoma that has returned or does not respond to treatment.
      Monoclonal antibodies, such as brentuximab vedotin, may find cancer cells and help kill them.
      Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop
      the growth of cancer cells, either by killing the cells or by stopping them from dividing.
      Giving brentuximab vedotin together with gemcitabine hydrochloride may kill more cancer
      cells.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To estimate the maximum tolerated dose (MTD) and/or recommended Phase 2 dose of
      brentuximab vedotin in combination with gemcitabine administered every three weeks to
      children with relapsed or primary refractory Hodgkin lymphoma (HL).

      II. To define and describe the toxicities of brentuximab vedotin in combination with
      gemcitabine administered on this schedule.

      III. To determine the complete response (CR) rate after treatment with four cycles of
      gemcitabine with brentuximab vedotin among patients with relapsed or refractory HL.

      SECONDARY OBJECTIVES:

      I. To preliminarily define the antitumor activity of brentuximab vedotin in combination with
      gemcitabine within the confines of a Phase 1 study.

      II. To describe the overall response rate (ORR) after 4 cycles of therapy among patients with
      relapsed or refractory HL.

      III. To describe the proportion of patients with HL able to mobilize an adequate yield of
      cluster of differentiation (CD) 34+ stem cells after gemcitabine with brentuximab vedotin.

      IV. To describe the relationship between disease response among patients with HL and changes
      in thymus and activation-regulated chemokine (TARC) during treatment, and to determine if
      specific micro ribonucleic acid (miRNA) profiles correlate with response to treatment.

      V. To describe the frequency of the Fc gamma receptor IIIa (FcγRIIIa)-158 valine
      (V)/phenylalanine (F) polymorphism among patients who experience pulmonary toxicity on this
      protocol.

      OUTLINE: This is a phase I, dose-escalation study of brentuximab vedotin followed by a phase
      II study. (Phase I completed as of amendment 4)

      Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1 and
      gemcitabine hydrochloride IV over 100 minutes on days 1 and 8. Treatment repeats every 21
      days for up to 15 more courses in the absence of disease progression or unacceptable
      toxicity. Patients with CR after any course may go off protocol therapy for stem cell
      transplant.

      After completion of study treatment, patients are followed up at 3, 6, 9, 12, 18, 24, 36, 48,
      and 60 months.
    

Intervention name(s): Brentuximab Vedotin; Gemcitabine Hydrochloride
Intervention type(s): Drug; Drug
Intervention description(s): Given IV; Given IV
Other intervention name(s): 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-vcMMAE; SGN-35; dFdCyd; Difluorodeoxycytidine Hydrochloride; FF 10832; FF-10832; FF10832; Gemcitabine HCI; Gemzar; LY-188011; LY188011
Intervention MeSH terms: Gemcitabine; Brentuximab Vedotin; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoconjugates
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment