Study of Atezolizumab Plus BEGEV Regimen in Relapsed or Refractory Hodgkin's Lymphoma Patients
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18-60
SponsorFondazione Italiana Linfomi - ETS
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
More than one prior systemic therapy for HL.
Presence of autoimmune disease (based on medical history): systemic lupus erythematosus, autoimmune thyroid disease (Hashimoto's thyroiditis, Basedow's disease), Sjögren's syndrome, glomerulonephritis, multiple sclerosis, rheumatoid arthritis, vasculitis, idiopathic pulmonary fibrosis (includine bronchiolitis obliterans organizing pneumonia) and inflammatory bowel disease (Crohn's disease, ulcerative colitis).
Previous skin toxicity (i.e. Steven-Johnson Sdr, severe skin reactions.
Prior allogeneic stem cell transplantation or prior solid organ transplant.
Trial design
Design model
Sequential
Treatments tested in this trial
Atezolizumab
DrugIn 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
Combination productIn 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.
Treatment groups
122 Participants
are divided into 3 treatment groupsGroup A: phase IExperimental treatment 2 interventions
Group B: phase IIb - arm AActive comparator 1 intervention
Group C: phase IIb - arm BExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
For Phase I part: evaluation of the maximum tolerated dose (MTD) of the atezolizumab.
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).
Time frame
During first cycle of treatment based on atezolizumab in combination with BEGEV in phase I study. Maximum time frame 17 months.2
For Phase II part: evaluation of the Complete Response Rate (CRR) before ASCT.
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.
Time frame
From initial treatment based on Atezolizumab and BEGEV to intensification treatment with ASCT. Time frame 4 months.Secondary outcomes
1
For Phase II part: evaluation of the overall response rate (ORR), partial response (PR), stable disease (SD) and progression disease (PD) rates.
The assessment of the overall response rate (ORR), partial response (PR), stable disease (SD) and progression disease (PD) rates will be performed according to the Lugano 2014 criteria and LYRIC 2016 criteria.
Time frame
The best response between the date of beginning of therapy and the last restaging. Time frame 14 months.2
For Phase II part: evaluation of the rate of partial response (PR) converted to Complete Response (CR).
The rate of PR converted to CR will be assessed as the number of PR converted in CR at the end of consolidation treatment with atezolizumab in the experimental arm.
Time frame
At the end of consolidation treatment with atezolizumab in the experimental arm. Time Frame 14 months.3
For Phase II part: evaluation of the peripheral blood stem-cell mobilization
The peripheral blood stem-cell mobilization will be assessed in patients receiving atezolizumab combined to BEGEV schedule. Adequate stem cells mobilization will be defined by the target cell harvesting of 3 x 1.000.000 CD34+ cells/kg.
Time frame
At the end of treatment based on atezolizumab and BEGEV. Time Frame 3 months.4
For Phase II part: evaluation of engraftment after ASCT
Engraftment will be assessed in patients who received ASCT after salvage treatment with atezolizumab combined to BEGEV. Engraftment will be defined as the first of three consecutive days of achieving a sustained peripheral blood neutrophil count of \>500 × 1.000.000/L. Platelet engraftment is usually defined as independence from platelet transfusion for at least 7 days with a platelet count of more than \>20 × 1.000.000.000/L.
Time frame
Between 30 and 60 days after ASCT: Time Frame 5 months.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Fondazione Italiana Linfomi - ETS
Lead sponsor
Roche Pharma AG
Collaborator
Source ClinicalTrials.gov