ATEZOLIZUMAB for Hodgkin lymphoma

Inclusion criteria

• {"criterion_text":"- 18-60 years old (upper limit valid only for phase I).\n- Histologically confirmed cHL: 1) at first disease relapse or refractory to a first-line treatment including: - ABVD/ABVD like regimen - BEACOPP/BEACOPP like regimen - BV-AVD regimen - ABVD/ABVD like (2 cycles) intensified with BEACOPP/BEACOPP like regimen due to persistence of disease at interim positron emission tomography (PET). 2) with documented persistent disease at interim PET (DS4-5) performed after 2 cycles of ABVD/ABVD like regimen.\n- Only one prior systemic therapy for Hodgkin’s lymphoma (HL).\n- Eligibility for ASCT.\n- Performance status (PS) ≤ 2 on the Eastern Cooperative Oncology Group (ECOG) scale.\n- Adequate haematological function, unless due to bone marrow involvement by lymphoma, at the moment of signing informed consent, defined as follows: • neutrophils >= 1.500/mmc and • platelets >=75.000/mmc and • haemoglobin >= 8,0 g/dL with transfusion independence\n- Capacity and willingness to adhere to study visit schedule and specific protocol procedures.\n- 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."}

Exclusion criteria

• {"criterion_text":"- More than one prior systemic therapy for HL.\n- 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).\n- Previous skin toxicity (i.e. Steven-Johnson Sdr, severe skin reactions.\n- Prior allogeneic stem cell transplantation or prior solid organ transplant.\n- History of active tubercolosis.\n- History of leptomeningeal disease.\n- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment.\n- Central nervous system (CNS) involvement by lymphoma.\n- Major surgery (excluding any lymph node biopsy) within 28 days prior to signing informed consent.\n- Seropositivity for HBV or evidence of active infection. The following categories may be considered for the study: • HBsAg positive with undetectable HBV DNA (inactive carriers). • HBsAg negative HBsAb positive and HBcAb negative (vaccinated patients) • HBsAg negative but HBcAb positive from previous infection, providing that they are given antiviral prophylaxis.\n- Seropositivity for HCV. Patients with presence of HCV antibody are eligible only if PCR result are negative for HCV RNA\n- Seropositivity for HIV.\n- 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.\n- Life expectancy lower than 6 months.\n- 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).\n- Any of the following laboratory abnormalities: liver enzymes (AST/SGOT and/or ALT/SGPT) > 3 fold the upper limit of normal (except of liver involvement by lymphoma); total bilirubin > 1.5 mg/dL (except for patients with known Gilbert’s disease or biliary tree compression by lymphoma masses); creatinine clearance < 30 mL/min.\n- 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.\n- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins\n- Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation\n- Pregnancy or breastfeeding, or unwillingness to comply with adequate contraception (one negative pregnancy test within 14 days prior to initiation of study treatment required).\n- 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 unacceptable risk if participating in the study."}

Primary endpoints

• {"endpoint_text":"- Phase I: Phase I: A DLT defined as any of these events occurring during C1 (initial 21 days): - G4 neutropenia leading to delay of next cycle of >14 days; - G4 thrombocytopenia or anemia leading to delay in the of the next cycle of >14 days; - G3 or 4 neutropenia with a fever>38.5 °C and/or infection requiring antibiotic or anti-fungal treatment for >14 days; - G≥3 non-hematologic toxicity persisting for >14 days and not related to study disease; -G≥3 infusion-related toxicities; G≥3 AESIs.","definition_or_measurement_approach":"DLT defined as any of the listed events occurring during Cycle 1 (initial 21 days), with specific grade thresholds and timing criteria as described in the endpoint text."}
• {"endpoint_text":"- Phase IIb: 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 (Appendix D). Patients without response assessment (due to whatever reason) will be considered as non-responders.","definition_or_measurement_approach":"CRR measured as proportion of patients achieving complete response after first 4 cycles per Lugano 2014 and LYRIC 2016; missing response assessments are counted as non-responders. Assessment by independent radiologic review committee (IRRC) described elsewhere in objectives."}

Secondary endpoints

• {"endpoint_text":"- Pahse IIb: ORR, PR, SD, PD rate will be defined according to the Lugano 2014 criteria and LYRIC 2016 criteria.","definition_or_measurement_approach":"Response rates defined per Lugano 2014 and LYRIC 2016 criteria."}
• {"endpoint_text":"- Phase IIb: number of PR converted in CR.","definition_or_measurement_approach":"Count of partial responses converting to complete responses during study treatment/consolidation."}
• {"endpoint_text":"- Phase IIb: Adequate stem cells mobilization will be defined by the target cell harvesting of 3 x 106 CD34+ cells/kg.","definition_or_measurement_approach":"Adequate mobilization defined as collection of ≥ 3 x 10^6 CD34+ cells/kg."}
• {"endpoint_text":"- Pahse IIb: Engraftment in patients receiving ASCT will be defined as the first of three consecutive days of achieving a sustained peripheral blood neutrophil count of >500 × 106/L (Wolff et al. 2002). Platelet engraftment is usually defined as independence from platelet transfusion for at least 7 days with a platelet count of more than >20 × 109/L (Teltschik et al. 2016).","definition_or_measurement_approach":"Neutrophil engraftment = first of three consecutive days with neutrophils >500×10^6/L; platelet engraftment = independence from platelet transfusion ≥7 days with platelets >20×10^9/L."}
• {"endpoint_text":"- Phase IIb: DoR will be defined as the time from date of documented tumor response (CR) until lymphoma relapse or progression.","definition_or_measurement_approach":"Duration of response measured from date of documented CR to relapse or progression."}
• {"endpoint_text":"- Pahse 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.","definition_or_measurement_approach":"PFS: time from treatment start to relapse/progression/death; OS: time from treatment start to death; censoring rules described."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Safety endpoints measured by incidence, type and grade of AEs/SAEs, withdrawal and hospitalization rates during study."}
• {"endpoint_text":"- Phase IIb: SUVmax, tMTV (total Metabolic Tumor Volume), TLG (Total Lesion Glycolysis), Dmax and Radiomics features extrapolated by PET scans","definition_or_measurement_approach":"Quantitative PET parameters (SUVmax, tMTV, TLG, Dmax) and radiomics features derived from PET scans as specified."}

Italy

Earliest CTIS Part Ii Submission Date

10-09-2024

Latest Decision Or Authorization Date

07-05-2026

Processing Time Days

604

Number Of Sites

26

Number Of Participants

140

Primary sponsor

Full Name

Fondazione Italiana Linfomi Ets

Organisation Type

Patient organisation/association

Country Of Registered Address

Italy

Third parties

• {"country":"","full_name":"Roche S.p.A.","duties_or_roles":"Monetary support","organisation_type":""}