NIVOLUMAB for Classical Hodgkin lymphoma|Early-stage classical Hodgkin lymphoma

Inclusion criteria

• {"criterion_text":"- Male or female patients aged 18-70.\n- Total bilirubin must be < 2.0 x the upper limit of normal (ULN) unless known Gilbert syndrome\n- ALT or AST must be < 3 x the upper limit of normal.\n- Female patients: if postmenopausal for at least 1 year before enrolment or, if fertile - agreeing to practice 2 effective methods of contraception or agreeing to practice true abstinence.\n- Male patients should agree to practice barrier contraception or to practice abstinence\n- Treatment-naïve, classical HL patients with Ann Arbor stage I or II A non-bulky disease stratified according to modified EORTC Criteria (refer to Appendix A);\n- Patients must have histologically confirmed classical HL according to the current World Health Organization Classification (nodular sclerosis, mixed cellularity, lymphocytes rich, lymphocytes depleted, or classical HL NOS [not otherwise specified];\n- ECOG performance status 0-2\n- Hemoglobin must be > 8 gr./dL\n- Absolute neutrophil count ≥ 1,000/μL\n- Platelet count ≥ 100,000/μL\n- Voluntary written consent to take part to the study\n- Serum Creatinine < 2.0 mg/dL and/or Creatinine clearance or calculated Creatinine clearance > 40 mL/minute"}

Exclusion criteria

• {"criterion_text":"- Composite lymphoma or nodular lymphocyte-predominant Hodgkin lymphoma;\n- Severely impaired, lung and renal function;\n- Diagnosed or treated for another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection;\n- Active autoimmune disorder in treatment with immunosuppressive drugs\n- A left-ventricular ejection fraction < 50%;\n- Myocardial infarction within 2 years of study entry.\n- Pregnancy or lactation\n- Bulky disease (Lugano 2014 definition: single or conglomerated nodal mass with the largest diameter measuring 10 or more centimeters);\n- B symptoms;\n- Extra nodal site involved by disease;\n- Female patients who are both lactating and breastfeeding or who have a positive serum pregnancy test during the screening period or a positive pregnancy test on Day 1 before first dose of study drug;\n- Uncompensated diabetes mellitus requiring insulin therapy;\n- Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol;\n- Known human immunodeficiency virus (HIV) infection with a positive search for HIV antigens by immunoblot and/or circulating copies of HIV-RNA;\n- Active hepatitis B with circulating copies of HBV-DNA, or active hepatitis C infection with circulating copies of HCV-RNA;"}

Primary endpoints

• {"endpoint_text":"- To evaluate the overall efficacy in terms of 3-Y PFS equal or superior to 90% , defined as the time from registration until first occurrence of disease progression or relapse, or death for any reason of chemotherapy alone in non-bulky stage I-IIA Hodgkin Lymphoma (eHL), patients with a very low risk of treatment failure, as defined by both a low Metabolic Tumor Volume (MTV) and a negative interim PET after 2 ABVD cycle (PET-2).","definition_or_measurement_approach":"3-Y PFS defined as time from registration until first occurrence of disease progression or relapse, or death for any reason; threshold of interest is PFS at 3 years (>= 90%) in the specified low-risk population."}

Secondary endpoints

• {"endpoint_text":"- To explore the efficacy in terms of 3-Y PFS defined as the time from registration until first occurrence of disease progression or relapse, or death for any reason of CMT plus Nivolumab in high-risk eHL, defined either by a positive PET-2 or a high baseline MTV or both.","definition_or_measurement_approach":"3-Y PFS defined as time from registration until progression, relapse, or death; measured in high-risk group (positive PET-2 and/or high baseline MTV) receiving combined modality treatment plus Nivolumab."}
• {"endpoint_text":"- To evaluate the efficacy, in terms of three-year freedom from second treatment Failure (3-Y FF2TF), measured from the date of registration to the date of second relapse after radiotherapy “on demand” to rescue patients relapsed after CT alone with the pattern of “limited relapse” for the entire group (relapsed and non-relapsed) of low-risk patients (with low MTV and negative PET2).","definition_or_measurement_approach":"3-Y FF2TF measured from registration to date of second relapse after rescue radiotherapy; assesses absence of second treatment failure at 3 years for the specified group."}
• {"endpoint_text":"- To evaluate the safety, in terms of 3-Y OS, defined as the time from enrollment until death for any reason of the delayed radiotherapy (RT ,,on demand”) followe by Nivolumab maintenance in rescuing patients who relapsed after chemotherapy alone with the pattern of ,,limited relapse”.","definition_or_measurement_approach":"3-Y overall survival defined as time from enrollment until death from any cause; applied to patients receiving delayed RT on demand followed by Nivolumab maintenance as rescue."}
• {"endpoint_text":"- Overall accuracy, sensitivity, specificity, negative predictive value and positive predictive value of cell-free DNA to detect an impending relapse during follow-up of patients treated with chemotherapy alone","definition_or_measurement_approach":"Diagnostic performance metrics (accuracy, sensitivity, specificity, NPV, PPV) of cfDNA assay to detect impending relapse during follow-up in patients treated with chemotherapy alone."}

Italy

Earliest CTIS Part Ii Submission Date

11-10-2024

Latest Decision Or Authorization Date

27-11-2024

Processing Time Days

47

Number Of Sites

15

Number Of Participants

40

Spain

Earliest CTIS Part Ii Submission Date

11-10-2024

Latest Decision Or Authorization Date

22-11-2024

Processing Time Days

42

Number Of Sites

14

Number Of Participants

65

Poland

Earliest CTIS Part Ii Submission Date

11-10-2024

Latest Decision Or Authorization Date

24-11-2024

Processing Time Days

44

Number Of Sites

7

Number Of Participants

40

Primary sponsor

Full Name

Medical University Of Gdansk

Organisation Type

Educational Institution

Country Of Registered Address

Poland