Brentuximab Vedotin in Refractory/Relapsed Hodgkin Lymphoma Treated by ICE
Condition: Hodgkin Disease
MeSH terms: Hodgkin Disease
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This study is designed as a phase Ib/II trial. The first part (phase Ib) is a dose escalation
      design to explore the safety and assess the recommended phase 2 dose of Brentuximab Vedotin
      in Hodgkin lymphoma patients treated with ICE regimen.

      The second part, depending on the selected dose after the completion of phase Ib part of the
      study, will further explore safety in addition to efficacy of the recommended dose of
      Brentuximab Vedotin in a selected population of patients treated with ICE with Hodgkin
      lymphoma.
    

Detailed description: 
      PHASE I:

      3 cycles of Brentuximab Vedotin ICE every 3 weeks and one cycle of Brentuximab Vedotin alone
      at the doses described below.

      Cohorts of between three and six evaluable patients will be recruited at each dose level.

      Dose escalation rules:

      Treat 3 patients at level K

        1. If 0 patients experience dose-limiting toxicity (DLT), escalate to dose K+1

        2. If 2 or more patients experience DLT, de-escalate to level K-1

        3. If 1 patient experiences DLT, treat 3 more patients at dose level K A. If 1 of 6
           experiences DLT, escalate to dose level K+1 B. If 2 or more of 6 experiences DLT,
           de-escalate to level K-1 Dose escalation will begin at level K.

      Level K:

      Brentuximab Vedotin: 1.2 mg/kg (cycle 1-3), 1.8 mg/kg (cycle 4) ICE (cycle 1-3): Etoposide
      100 mg/m² (day1 to 3); Carboplatine max 800mg (day 2); Ifosfamide + Mesna 5 g/m² (day 2)

      Level K -1:

      Brentuximab Vedotin: 0.8 mg/kg (cycle 1-3), 1.8 mg/kg (cycle 4) ICE (cycle 1-3): Etoposide
      100 mg/m² (day1 to 3); Carboplatine max 800mg (day 2); Ifosfamide + Mesna 5 g/m² (day 2)

      Level K +1:

      Brentuximab Vedotin: 1.8 mg/kg (cycle 1-3), 1.8 mg/kg (cycle 4) ICE (cycle 1-3): Etoposide
      100 mg/m² (day1 to 3); Carboplatine max 800mg (day 2); Ifosfamide + Mesna 5 g/m² (day 2)

      Dose finding rule:

      Provisional dose levels are listed in previous tables. Dose-escalation will continue until
      Maximal Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) is reached or the full doses
      of BV and ICE are delivered without DLT

      PHASE II:

      3 cycles of Brentuximab Vedotin + ICE every 3 weeks and one cycle Brentuximab Vedotin alone.

      The recommended dose of BV and ICE will be determined by the phase I Brentuximab Vedotin: MTD
      mg/kg (cycle 1-3), 1.8 mg/kg (cycle 4) ICE (cycle 1-3): Etoposide 100 mg/m² (day1 to 3);
      Carboplatine max 800mg (day 2); Ifosfamide + Mesna 5 g/m² (day 2) The recommended dose of BV
      and ICE will be determined by the phase I.
    

Intervention name(s): Brentuximab Vedotin; Etoposide; Carboplatine; Ifosfamide
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Phase I:
Cohort K: BV on Day 1: 1.2 mg/kg (cycle 1-3) and 1.8 mg/kg (cycle 4) Cohort K+1: BV on Day 1: 1.8 mg/kg (cycle 1-3) and 1.8 mg/kg (cycle 4) Cohort K-1: BV on Day 1: 0.8 mg/kg (cycle 1-3) and 1.8 mg/kg (cycle 4)
Phase II:
BV on Day 1: at the Maximal Tolerated Dose (MTD) defined at Phase I; 100 mg/m² Days 1-2-3 of Cycles 1-2-3; max 800mg Day 2 of Cycles 1-2-3; 5 g/m² Day 2 of Cycles 1-2-3
Other intervention name(s): BV; SGN35
Intervention MeSH terms: Etoposide; Ifosfamide; Brentuximab Vedotin; Carboplatin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Relapsed; Refractory