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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
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
Clinique Universitaire Saint-Luc
Brussels, Belgium
CHU Dinant Godinne
Yvoir, Belgium
Phase I : Maximal Tolerated Dose (MTD) determination
To determine the MTD and/or Recommended Phase II dose (RP2D dose) of BV when administered to adult patients treated with ICE in refractory or relapsed Hodgkin's lymphomas.
Time frame: 4 months
Phase II = fraction of responding patients according to Lugano classification (metabolic Complete Response)
To evaluate the efficacy of BV in patient treated with ICE as first salvage treatment (establish the fraction of responding patients - metabolic Complete Response (CR)) as judged by the center by Lugano classification after the second cycle
Time frame: 2 months
Phase I : Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
To characterize the safety and tolerability of BV in patient treated with ICE.
Time frame: 4 months
Phase I = Preliminary Overall Response Rate (ORR)
To assess preliminary anti-tumor activity of BV in patient treated with ICE.
Time frame: 4 months
Phase II = ORR
To assess the ORR (Complete Response and Partial Response) after 3 cycles of BV and ICE and one cycle of BV
Time frame: 4 months
Phase II : Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
To assess the toxicity profile of BV in patient treated with ICE
Time frame: 4 months
Phase II = number of patients with hematological recovery after each cycle
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Purpose
TREATMENT
Masking
NONE
Enrollment
53
5 g/m² Day 2 of Cycles 1-2-3
Institut d'Hématologie de Basse Normandie - CHU Côte de Nacre
Caen, France
APHP-Hôpital Henri Mondor
Créteil, France
CHU de Dijon - Hôpital le Bocage
Dijon, France
CHRU Lille - Hôpital Claude Huriez
Lille, France
Centre Léon Bérard
Lyon, France
CHU Saint Eloi
Montpellier, France
CHU De Nantes
Nantes, France
Hôpital Necker
Paris, France
...and 9 more locations
To assess hematological recovery after each cycle of BV and ICE
Time frame: 4 months
Phase II = Feasibility of Autologous Stem Cell Transplant (ASCT) after BV-ICE = fraction of patients for whom harvest is possible
To assess the feasibility of harvesting an autologous peripheral blood stem cell graft after BV in patient treated with ICE
Time frame: 4 months
Phase II = Fraction of patients eligible for ASCT
To assess the fraction of patients (Complete Response/Partial Response) eligible for ASCT who actually underwent one or two ASCT
Time frame: 4 months
Phase II = Number of patients Positron Emission Tomography (PET) 4- after PET 2+
To assess the number of patients with PET 4 negative if the PET 2 is positive
Time frame: 4 months
Phase II = Progression Free Survival (PFS)
Number of participants who did not progressed after 2 years
Time frame: 2 years
Phase II = Overall Survival (OS)
Number of participants alive after 2 years
Time frame: 2 years