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 phase 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.~Patients with documented CR following ASCT will receive a consolidation therapy with atezolizumab as single agent every 4 weeks for 6 doses, starting preferably between 60 and 90 days, but ≥ 60 days and not > 120 days after autografting. In patients not previously radiotreated, adjuvant radiotherapy (RT) should be planned during consolidation treatment within the start of second consolidation dose, according to clinician's judgment and response assessment. RT will be administered at 30-36 Gy on sites of initial bulky disease or on single PET positive residual site.~Patients reaching PR after four cycles of atezolizumab combined with BEGEV or with documented PR after ASCT may continue the study protocol according to the physician judgment.~Dosing starts at 1200 mg and decreases in the successive cohort to the dose of 840 mg and 600 mg, according to Flow chart A. in the section 6 of the protocol.~In the consolidation phase atezolizumab will be administered at dose of 1200 mg every 4 weeks for 6 doses without dose reduction, but only delay or discontinuation.~Patients included in the cohort developing DLT, withdraw the protocol due to toxicity and continue the treatment according to good clinical practice.~For patients included in the cohort of MTD, monitoring and collection of AEs will be continuous during induction, consolidation treatment and follow-up.~The phase IIb part (expansion cohort) plans to randomize 122 patients in two arms (A and B, 61 per arm):~arm A will receive the BEGEV regimen followed by ASCT for patients achieving CR.~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.~In patients not previously radiotreated, adjuvant RT should be planned for both patients in arm A and arm B according to clinician's judgment and response assessment. RT will be administered at 30-36 Gy on sites of initial bulky disease or on single PET positive residual site.~Patients reaching PR after four induction cycles (atezolizumab combined with BEGEV or BEGEV alone) or with documented PR after ASCT may continue the study protocol according to the physician judgment.~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. Disease status, survival outcome, secondary primary malignancies and late toxicity will be collected every 6 months until patient withdrawal of consent, lost to follow up and patient's death. Long term follow-up phase will end 18 months after the end of phase IIb.
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):~arm A will receive the BEGEV regimen followed by ASCT for patients achieving CR.~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.