Study of Atezolizumab Plus BEGEV Regimen in Relapsed or Refractory Hodgkin's Lymphoma Patients
Condition(s) studied
Investigational drug(s) / intervention(s)
Atezolizumab: In phase I study: Atezolizumab will be administered until the determination of its MTD when combined with BEGEV schedule. In phase II b study - arm A (standard): Atezolizumab will not be administered. In phase II b study - arm B (experimental): Atezolizumab will be administered at MTD determined in phase I study plus BEGEV regimen (at dosages performed by local practice).
BEGEV: In phase I study: Atezolizumab will be administered until the determination of its MTD when combined with BEGEV schedule. In phase II b study - arm A (standard): only BEGEV will be administered. In phase II b study - arm B (experimental): BEGEV regimen will be administered in combination with Atezolizumab at MTD determined in phase I.
Study summary
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.
Eligibility
Primary outcome measure(s)
- For Phase I part: evaluation of the maximum tolerated dose (MTD) of the atezolizumab. — During first cycle of treatment based on atezolizumab in combination with BEGEV in phase I study. Maximum time frame 17 months.
The maximum tolerated dose (MTD) of the atezolizumab in combination with BEGEV will be established in the first cycle of therapy, in order to determine the recommended phase II dose (RP2D). Patients will be accrued in 3 patients cohorts at each dose level, starting from level 1. Dose de-escalation will be performed following the standard 3+3 rule, registering any Dose Limiting Toxicity (DLT). - For Phase II part: evaluation of the Complete Response Rate (CRR) before ASCT. — From initial treatment based on Atezolizumab and BEGEV to intensification treatment with ASCT. Time frame 4 months.
The assessment of CRR before ASCT will be performed by an independent radiologic review committee (IRRC) according to the Lugano classification response criteria (2014) and the LYmphoma Response to Immunomodulatory Therapy Criteria (LYRIC 2016). CRR will be defined as the proportion of patients in CR after the first 4 cycles of induction treatment, according to Lugano classification response Criteria and LYRIC 2016 criteria. Patients without response assessment (due to whatever reason) will be considered as non-responders.
Trial sites (28)
| Facility | City | Region | Status |
|---|---|---|---|
| S.C. Ematologia - A.O. SS. Antonio e Biagio e Cesare Arrigo | Alessandria | Alessandria | |
| Ematologia - Fondazione del Piemonte per l'Oncologia - IRCCS | Candiolo | Turin | |
| S.C. Ematologia e Trapianto emopoietico - Azienda Ospedaliera S.Giuseppe Moscati | Avellino | Italy | |
| Divisione di Oncologia e dei Tumori immuto-correlati - IRCCS Centro di Riferimento Oncologico di Aviano | Aviano | Italy | |
| U.O.C Ematologia - IRCCS Istituto Tumori Giovanni Paolo II | Bari | Italy | |
| Ematologia - ASST Spedali Civili di Brescia | Brescia | Italy | |
| Ematologia - Ospedale Vito Fazzi | Lecce | Italy | |
| IRCCS Istituto Romagnolo per lo studio dei Tumori "Dino Amadori" - IRST S.R.L. - Ematologia | Meldola | Italy | |
| Ematologia - Fondazione IRCCS Istituto Nazionale dei Tumori di Milano | Milan | Italy | |
| SC Ematologia - ASST Grande Ospedale Metropolitano Niguarda | Milan | Italy | |
| Istituto Nazionale Tumori - IRCCS Fondazione G. Pascale - UOC Ematologia Oncologica | Naples | Italy | |
| U.O. Onco-ematologia - Presidio ospedaliero "A. TORTORA" | Pagani | Italy | |
| Divisione di Ematologia - A.O. Ospedali Riuniti Villa Sofia-Cervello | Palermo | Italy | |
| Div. di Ematologia - IRCCS Policlinico S. Matteo di Pavia | Pavia | Italy | |
| Azienda USL Piacenza - UOC Ematologia e Centro Trapianti | Piacenza | Italy | |
| Ospedale delle Croci - Ematologia | Ravenna | Italy | |
| Ematologia - Azienda Unitа Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova | Reggio Emilia | Italy | |
| Ospedale degli Infermi di Rimini - U.O. di Ematologia | Rimini | Italy | |
| Ematologia - Ospedale S. Camillo | Roma | Italy | |
| Istituto Ematologia -Dipartimento di Medicina Traslazionale e di Precisione - Policlinico Umberto I - Università "La Sapienza" | Roma | Italy | |
| Policlinico Universitario Campus Bio-Medico - Ematologia - Trapianto cellule staminali - Medicina Trasfusionale e Terapia cellulare | Roma | Italy | |
| Universitа Cattolica S. Cuore - Ematologia | Roma | Italy | |
| U.O. Ematologia - Istituto Clinico Humanitas | Rozzano | Italy | |
| S.C. Oncoematologia - A.O. S. Maria di Terni | Terni | Italy | |
| A.O.U. Citta della Salute e della Scienza di Torino - Ematologia Universitaria | Torino | Italy | |
| S.C.Ematologia - A.O.U. Città della Salute e della Scienza di Torino | Torino | Italy | |
| A.O. C. Panico - U.O.C Ematologia e Trapianto | Tricase | Italy | |
| Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - SC Ematologia | Trieste | Italy |
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This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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