NCT02686346

Brentuximab Vedotin in Refractory/Relapsed Hodgkin Lymphoma Treated by ICE

Phase I/II Feasibility Study of Brentuximab Vedotin in Refractory / Relapsed Hodgkin Lymphoma Patients Who Are Treated by Chemotherapy (ICE) in Second Line and Eligible for Autologous Transplantation

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 53 (actual)
• Sponsor: The Lymphoma Academic Research Organisation · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Hodgkin Disease

Interventions

Type	Name	Description
DRUG	Brentuximab Vedotin	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
DRUG	Etoposide	100 mg/m² Days 1-2-3 of Cycles 1-2-3
DRUG	Carboplatine	max 800mg Day 2 of Cycles 1-2-3
DRUG	Ifosfamide	5 g/m² Day 2 of Cycles 1-2-3

Timeline

• Start date: 2016-03-01
• Primary completion: 2018-10-31
• Completion: 2021-07-12
• First posted: 2016-02-19
• Last updated: 2021-12-07

Locations

19 sites across 2 countries: Belgium, France