A Phase I/II b (Randomized Controlled) Study of Atezolizumab Combined to BEGEV Regimen as First Salvage Treatment in Patients With Relapsed or Refractory Hodgkin's Lymphoma Candidate to Autologous Stem-Cell Transplantation
The phase I part (safety assessment of the combination treatment) is aimed at determining the MTD of atezolizumab when combined with BEGEV schedule. 6-18 patients enrolled in this part will be treated with atezolizumab in combination with BEGEV regimen every 3 weeks for 4 cycles. Patients without a DLT in the first cycle and without disease progression after cycle 2, will undergo stem cell mobilization with 3-4 cycle of A-BEGEV + granulocyte colony-stimulating factor (G-CSF) and subsequently receive a myeloablative therapy followed by ASCT. The phase IIb part (expansion cohort) plans to randomize 122 patients in two arms (A and B, 61 per arm): 1. arm A will receive the BEGEV regimen followed by ASCT for patients achieving CR. 2. arm B will receive combination treatment with Atezolizumab and BEGEV regimen followed for patients reaching CR by ASCT plus a consolidation with 6 doses of atezolizumab at 1200 mg every 4 weeks. After the last treatment date of the last patient (LPLT), the phase IIb will be ended. A long term follow up will start, in order to better assess patients' prognosis. All evaluable patients from phase I and phase IIb study will enter in the long term follow up phase and will be followed for 18 months.
• 18-60 years old (upper limit valid only for phase I).
• Histologically confirmed cHL, at first disease relapse or refractory to a first-line treatment or with documented persistent disease at interim positron emission tomography (PET) performed after 2 cycles of first line (ABVD/ABVD like/BEACOPP).
• Only one prior systemic therapy for Hodgkin's lymphoma (HL).
• First disease relapse or refractory to a first-line treatment.
• Eligibility for ASCT.
• Performance status (PS) ≤ 2 on the Eastern Cooperative Oncology Group (ECOG) scale.
• Adequate haematological function, unless abnormalities due to underlying disease, at the moment of signing informed consent, defined as follows:
‣ neutrophils \> or = 1.500/mmc and
⁃ platelets \> or = 75.000/mmc and
⁃ haemoglobin \> or = 8,0 g/dL with transfusion independence
• Capacity and willingness to adhere to study visit schedule and specific protocol procedures.
• Compliance with effective contraception without interruption, according to physician's judgement, from 28 days before treatment start up to at least 6 months after treatment discontinuation, agreeing not to donate semen/eggs during treatment and for at least 6 months after last treatment dose.