Refractory/relapsed Hodgkin Lymphoma. MedDRA version: 21.0 Level: PT Classification code 10020233 Term: Hodgkin's disease mixed cellularity recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: TECENTRIQ - 840 MG - CONCENTRATO PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO - FLACONCINO (VETRO) - 20 ML (60 MG/ML) - 1 FLACONCINO
Product Name: Atezolizumab
Product Code: [IMP2]
Pharmac
Sponsors
FONDAZIONE ITALIANA LINFOMI ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - 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) minor or equal to 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 majour or equal to 1.500/mmc and • platelets majour or equal to75.000/mmc and • haemoglobin majour or equal to 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, from 28 days before treatment start up to 3 months after treatment discontinuation, agreeing not to donate semen/eggs during treatment and for 3 months after last treatment dose. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 80 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: - 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. - History of active tubercolosis. - History of leptomeningeal disease. - Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. - Central nervous system (CNS) involvement by lymphoma. - Major surgery (excluding any lymph node biopsy) within 28 days prior to signing informed consent. - Seropositivity for HBV or evidence of active infection. The following categories may be considered for the study: • HBsAg positive with HBV DNA minor to 2000 UI/ml (inactive carriers); HBV DNA majour to2000 UI/ml is criteria of exclusion • HBsAg negative but HBsAb positive • HBsAg negative but HBcAb positive HBsAg positive with HBV DNA minor to 2000 UI/ml and HBsAg negative but HBcAb positive will be eligible for the study only if they accept to receive antiviral prophylaxis for all the period of treatment and at least for 12 months after the end of therapy. Treatment should be stopped in case of hepatitis reactivation. - Seropositivity for HCV. Patients with presence of HCV antibody are eligible only if PCR result are negative for HCV RNA - Seropositivity for HIV. - Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail bed) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics except if for tumor fever) within 2 weeks of the start of Cycle 1. - Life expectancy lower than 6 months. - Prior history of malignancies, other than HL, unless the patient has been free for at least 5 years (exceptions: localized non-melanoma skin cancer ad carcinoma in situ of the cervix). - Any of the following laboratory abnormalities: liver enzymes (AST/SGOT and/or ALT/SGPT) majour to 3 fold the upper limit of normal (except of liver involvement by lymphoma); total bilirubin majour to 1.5 mg/dL (except for patients with known Gilbert’s disease or biliary tree compression by lymphoma masses); creatinine clearance minor to 30 mL/min. - Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina. - History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins - Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation - Pregnancy or breastfeeding, or unwillingness to comply with adequate contraception (one negative pregnancy test within 14 days prior to initiation of study treatment required). - Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent the patient from signing the informed consent or which may place the patient at unac
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: PHASE I: To determine the maximum tolerated dose (MTD) of the atezolizumab in combination with BEGEV, established in the first cycle of therapy, in order to determine the recommended phase II dose (RP2D). PHASE IIb: To assess the CRR before ASCT according to the Lugano classification response criteria (2014) and the LYmphoma Response to Immunomodulatory Therapy Criteria (LYRIC 2016) by an independent radiologic review committee (IRRC) assessment.;Secondary Objective: PHASE IIb: 1) to assess the overall response rate (ORR), partial response (PR), stable disease (SD) and progression disease (PD) rates. 2) to assess the rate of PR converted to CR at the end of consolidation treatment with atezolizumab in the experimental arm. 3) to assess the peripheral blood stem-cell mobilization in patients receiving atezolizumab combined to BEGEV schedule. 4) to assess engraftment in patients who received ASCT after salvage treatment with atezolizumab combined to BEGEV. 5) to assess the duration of response (DoR). 6) to assess PFS and overall survival (OS) for all patients and for patients achieving CR; also in long-tem follow up. 7) to assess the safety and the tolerability of a first salvage treatment based on the combination of intravenous atezolizumab and BEGEV regimen in patients affected by relapsed or refractory cHL.;Primary end point(s): For Phase I: A dose-limiting toxicity (DLT) is defined as any of the following events occurring during cycle 1 (the initial 21 days): - Grade 4 neutropenia leading to a delay in the start of the next cycle of more than 14 days; - Grade 4 thrombocytopenia or anemia leading to a delay in the start of the next cycle of more than 14 days; - Grade 3 or 4 neutropenia with a fever majour of 38.5 °C and/or infection requiring antibiotic or anti-fungal treatment for more than 14 days; - Grade majour or equal to 3 non-hematologic toxicity (laboratory value: creatinine, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic py | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: After ASCT in patients who received salvage treatment with atezolizumab combined to BEGEV.; From the beginning of treatment to the last response evaluation.; At the end of consolidation treatment with atezolizumab in the experimental arm.; Dopo atezolizumab combinato con il programma BEGEV.; From date of documented tumor response (CR) until lymphoma relapse or progression.; For PFS: from beginning of therapy until lymphoma relapse or progression or death as a result of any cause. For OS: from beginning of therapy until death as a result of any cause.; Form enrollment to drop out of the patient form the study.;Secondary end point(s): For phase IIb: ORR, PR, SD, PD rate will be defined according to the Lugano 2014 criteria and LYRIC 2016 criteria.; Per la fase IIb: number of PR converted in CR.; For phase IIb: Adequate stem cells mobilization will be defined by the target cell harvesting of 3 x 106 CD34+ cells/kg.; For phase IIb: DoR will be defined as the time from date of documented tumor response (CR) until lymphoma relapse or progression.; For phase IIb: PFS will be defined as the time from beginning of therapy until lymphoma relapse or progression or death as a result of any cause; responding patients and patients who are lost to follow up will be censored at their last assessment date. OS will be defined as the time from beginning of therapy until death as a result of any cause; alive patients and those who are lost to follow up will be censored at their last assessment date.; For phase IIb: measurement of: patients’ withdrawal rate, incidence, type and grade of any adverse event (AE) and serious adverse event (SAE), hospitalization rate (except it for study therapy administration), throughout the study. | — |
Countries
Italy
Contacts
Public ContactUffici studi FIL
Fondazione Italiana Linfomi Onlus
Outcome results
None listed