The Fondazione Italiana Linfomi has launched a comprehensive multicenter clinical trial to evaluate whether structured lifestyle interventions can improve quality of life outcomes in long-term lymphoma survivors. The prospective randomized open-label study, designated NCT05934084, aims to recruit 552 patients across 40 Italian medical centers to assess the impact of a healthy Lifestyle implemented Survivorship Care Plan (LS-SCP).
Study Design and Patient Population
The trial targets a specific population of young lymphoma survivors who were diagnosed between ages 18-50 and have achieved complete remission following first-line therapy. Eligible participants must have been in remission for a minimum of 3 years and maximum of 10 years since their last treatment. The study focuses on three lymphoma subtypes: classical Hodgkin lymphoma (cHL), diffuse large B-cell lymphoma (DLBCL), and primary mediastinal large B-cell lymphoma (PMBCL).
Participants must have received at least 200 mg/m² cumulative doxorubicin/adriamycin dose, equivalent to four cycles of chemotherapy. Standard first-line treatments include ABVD or BEACOPP regimens for Hodgkin lymphoma, R-CHOP for DLBCL, and R-CHOP or R-DA-EPOCH for PMBCL.
Intervention Protocol
The experimental arm receives a comprehensive 6-month intervention combining survivorship care planning, nutritional guidance, and physical activity recommendations. Patients undergo bi-monthly automatic calls to assess compliance with the LS-SCP protocol. The control arm follows standard clinical practice without specific survivorship interventions.
Comprehensive Assessment Framework
The study employs multiple validated assessment tools to evaluate outcomes. The primary endpoint measures global quality of life using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). This 30-item instrument includes five functioning scales, nine symptom scales, and a global health status scale, with higher scores indicating better health-related quality of life for functioning scales.
Secondary assessments include the 12-Item Short Form Survey (SF-12) for evaluating health impact on daily life, with scores ranging from 0 to 100. The Mediterranean Literature (MEDI-LITE) questionnaire assesses dietary adherence, with final scores varying from 0 (low adherence) to 18 (high adherence). Physical activity is measured using the International Physical Activity Questionnaire (IPAQ), calculating MET minutes per week with walking valued at 3.3 METS, moderate activity at 4 METS, and vigorous activity at 8 METS.
Cognitive and Psychological Evaluation
The trial incorporates cognitive assessment through the Cognitive Functioning Self-Assessment Scale (CFSS), an 18-item questionnaire covering attention, memory, and spatial-temporal orientation domains. Participants rate activities of daily living on a 5-point frequency scale, with higher scores indicating worse self-perceived cognitive functioning.
Psychological well-being is evaluated using the Hospital Anxiety and Depression Scale (HAD-S), which includes seven items each for depression and anxiety subscales. Scores range from zero to three per item, with total subscale scores above 8 points indicating considerable symptoms.
Clinical Monitoring and Safety
The study includes comprehensive clinical monitoring with assessments at baseline, 6 months, and 12 months post-randomization. Participants undergo echocardiogram and 2D speckle-tracking echocardiography within three months of enrollment. The trial excludes patients with significant cardiovascular disease, including grade 2 or higher arrhythmia, hypertension, or left ventricular dysfunction.
Hand grip muscle strength is measured using dynamometry, and body mass index is calculated from weight and height measurements. The study tracks compliance with screening for secondary cancers and vaccination protocols, along with monitoring for cardiovascular disease and other comorbidities.
Exclusion Criteria and Safety Considerations
The trial excludes patients with secondary cancer diagnoses except non-melanoma skin cancers and adequately treated cervical carcinoma in situ. Patients who received second-line chemotherapy or stem cell transplant are ineligible. Additional exclusions include inability to perform physical activity, grade 3 or higher neuropathy, vertebral fractures, and various cardiovascular conditions.
Recent venous thromboembolism, arterial thrombosis, or grade 2 or higher bleeding within six months disqualifies participants. Chronic lymphedema, rheumatic disease requiring systemic treatment, pleural effusion, and pregnancy also constitute exclusion criteria.
Study Endpoints and Duration
The trial's 30-month duration allows for comprehensive evaluation of intervention effects. Primary analysis focuses on changes in global quality of life scores, while secondary endpoints include metabolic outcomes such as diabetes prevalence and BMI changes. The study measures adherence to healthy lifestyle factors and compliance with prescribed interventions.
Overall survival is tracked as a secondary endpoint, along with frequencies of chronic fatigue assessed through the Fatigue Assessment Scale (FAS) and Chronic Fatigue Syndrome Self-assessment (CFSS). The trial evaluates negative lifestyle factors associated with cardiotoxicity and metabolic syndrome development.
