Pagani

Researchers are conducting a large prospective, observational cohort study to evaluate the clinical impact of new Monoclonal Antibodies MAB in patients with B-cell Non-Hodgkin Lymphoma NHL treated in Italian clinical practice. The study focuses on collecting information about the use, feasibility, effectiveness, and both short- and long-term side effects of novel MABs that have been approved by the European Medicines Agency since 2020 and prescribed according to authorized indications in Italy. Participants will be divided into groups based on treatment indication, antibody type, and lymphoma subtype to allow detailed analysis. The study observes patients with B-cell NHL who have received at least one dose of a novel MAB either alone or in combination, as authorized for use in Italy. Both patients receiving first-line treatment and those with relapsed or refractory disease are included. Various cohorts and sub-cohorts will be analyzed to understand outcomes by indication, antibody type, and histological subtype, providing a comprehensive overview of these treatments in real-life settings. Participants will be followed for at least five years to assess outcomes such as overall response rate, complete response rate, progression-free survival, overall survival, event-free survival, time to next treatment, non-relapse mortality, duration of response, and the incidence of early and late adverse events. Clinical data collection will include treatment details, safety monitoring, and long-term follow-up to evaluate both effectiveness and toxicity. The study spans several years, allowing researchers to capture extensive real-world evidence on novel MAB use in B-cell NHL.

Researchers are evaluating the effectiveness and safety of combining sonrotoclax with either obinutuzumab or rituximab compared to venetoclax plus rituximab in adults with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma CLLSLL. This Phase 3 randomized study aims to understand which combination offers better progression-free survival and treatment outcomes in patients who have undergone prior therapies. The study has four treatment groups sonrotoclax combined with obinutuzumab, sonrotoclax combined with rituximab, sonrotoclax plus obinutuzumab with treatment guided by minimal residual disease evaluation, and venetoclax combined with rituximab. Sonrotoclax and venetoclax are given orally, while obinutuzumab and rituximab are administered intravenously. Participants receive these treatments according to their assigned group as part of this clinical research. Participants will be monitored for progression-free survival, overall survival, response rates, and minimal residual disease status over several months up to several years. Safety assessments include tracking treatment-emergent adverse events. Quality of life and symptom burden will be evaluated using questionnaires. The study involves regular visits for treatment administration and assessments, with follow-up extending up to 84 months to observe long-term outcomes.

The trial investigates treatment options for adults aged 18 to 70 with newly diagnosed higher-risk myelodysplastic syndromes HR-MDS, focusing on the feasibility of allogeneic stem cell transplantation HSCT. It compares upfront HSCT with pre-treatment using azacitidine or conventional chemotherapy based on the patients bone marrow blast counts. This phase III, open-label, randomized multicenter study aims to determine whether pre-transplant treatments affect the ability to proceed with HSCT. Participants are assigned to groups depending on their bone marrow blast levels. Those with 10% or more blasts receive either conventional chemotherapy following a 37 protocol or azacitidine given subcutaneously at 75 mgm2 daily for 7 days every 28 days for at least 4 cycles before HSCT if a suitable donor is available. Patients with less than 10% blasts may receive upfront HSCT or azacitidine prior to HSCT under similar dosing schedules. The study evaluates these different sequences of therapy to assess HSCT feasibility. During the study, participants undergo regular assessments over four years to monitor whether they proceed to HSCT. Researchers track treatment outcomes, safety, and overall feasibility by measuring the proportion of randomized patients who receive the transplantation. The trial includes follow-up for at least four years to collect data on these outcomes and ensure participant safety and treatment adherence throughout the process.

Researchers are evaluating the effect of adding gemtuzumab ozogamicin to standard chemotherapy for adults aged 18 to 60 with newly diagnosed favorable or intermediate-risk acute myeloid leukemia AML. This phase 3 study aims to reduce minimal residual disease MRD levels before transplantation and assess whether MRD-driven post-remission therapy can improve anti-leukemic outcomes. The study excludes patients with certain genetic markers or prior treatments to focus on a specific AML subgroup. Participants receive induction treatment with gemtuzumab, daunorubicin, and cytosine arabinoside, followed by consolidation therapy with adjusted doses of these drugs. After consolidation, patients undergo either autologous or allogeneic stem cell transplantation based on their MRD level. This MRD-guided approach helps tailor the intensity of post-remission therapy. Throughout the study, participants undergo MRD assessments to measure treatment activity, with the primary outcome being MRD negativity two months after starting therapy. Researchers also monitor kidney and liver function, heart health, and overall compliance with study procedures. The study involves regular clinical observations and assessments to evaluate the effectiveness of the combined treatment and its impact on MRD levels over time.

Researchers are evaluating the safety and effectiveness of tucatinib combined with trastuzumab and capecitabine in adult women with HER2-positive metastatic breast cancer in a real-world setting. This observational study includes patients who have previously received multiple HER2-targeted treatments and aims to understand how this combination therapy works outside of clinical trials. HER2 is a protein that promotes cancer cell growth and is overexpressed in about 20% of breast cancers. Tucatinib is an oral drug that selectively inhibits the HER2 protein, and this study follows approved treatment guidelines and doses. Patients will receive tucatinib, trastuzumab, and capecitabine as prescribed by their doctors according to local clinical practice without any additional treatment procedures mandated by the study. The study is non-interventional and multicenter, enrolling about 300 women who are candidates for tucatinib therapy, including those with prior treatments such as trastuzumab, pertuzumab, T-DM1, and T-DXd. Patients will be observed during their treatment period and followed for 18 months after finishing tucatinib therapy to monitor outcomes and safety. During the study, researchers will collect baseline data, safety information, and performance status using the Eastern Cooperative Oncology Group ECOG score. They will assess response to treatment and survival based on clinicians evaluations and local practice. Follow-up will include monitoring for symptoms, treatment response, and survival status for 18 months post-treatment. The study also records any treatments patients receive before or after tucatinib therapy to better understand its real-world effectiveness and safety.

Researchers are evaluating how a healthy lifestyle implemented through a Survivorship Care Plan LS-SCP may affect the quality of life for long-term lymphoma survivors who have been in remission for at least three years and up to ten years. The study focuses on patients with classical Hodgkin lymphoma, Diffuse Large B-cell lymphoma DLBCL, or Primary mediastinal large B-cell lymphoma PMBCL who have completed first-line therapy and are aged between 18 and 50 years. This randomized, open-label, multicenter trial aims to understand the impact of lifestyle changes on survivors well-being over time. Participants are randomly assigned to one of two groups the experimental arm receives a Survivorship Care Plan including a nutritional plan and physical activity guidance for six months, with bi-monthly automated calls to support adherence. The control arm receives no specific intervention and follows standard clinical care with self-administered questionnaires at 6 and 12 months. Both groups complete assessments using validated questionnaires at baseline, 6 months, and 12 months to evaluate various health and quality of life measures. During the study, participants undergo clinical assessments and complete questionnaires such as the EORTC QLQ-C30, SF12, MEDI-LITE, Chronic Fatigue Syndrome Self-assessment, Fatigue Assessment Scale, and Hospital Anxiety and Depression Scale. Researchers will monitor outcomes including global quality of life, psychosocial well-being, fatigue frequency, cognitive function, metabolic health, cardiovascular events, adherence to healthy behaviors, and overall survival for up to 30 months from study start. The study includes safety follow-up and compliance tracking to understand how lifestyle interventions might support long-term health in lymphoma survivors.

Researchers are investigating advanced follicular lymphoma FL by studying the role of EZH2 gene changes in patients treated with immunochemotherapy. This study is linked to the FILFOLL12 trial, which enrolled 807 patients and compared first-line treatments using chemoimmunotherapy combinations like R-CHOP or bendamustine-rituximab BR. The goal is to find biomarkers that can guide doctors in selecting the best chemotherapy approach for each patient. The study involves analyzing biological samples such as bone marrow, peripheral blood, and diagnostic tumor tissue. Tests include detecting EZH2 mutations using droplet digital PCR and examining gene expression patterns with RNA sequencing. Researchers will also explore other markers related to disease diversity, minimal residual disease, genetic factors, and microbiome profiles. These tests build on samples collected during the original FILFOLL12 trial. Participants have already been enrolled in the FILFOLL12 trial and provided biological samples. Researchers will measure outcomes like progression-free survival up to 43 months after treatment start, response rates within several months, and the relationship between gene mutations and expression patterns. The study is observational and focuses on laboratory analyses without additional treatments. It aims to provide practical biomarkers for clinical use and establish a network of laboratories for timely testing.

This research aims to evaluate the effects of adding Vitamin D supplementation to standard immunochemotherapy in elderly patients diagnosed with Diffuse Large B-Cell Lymphoma or Follicular grade IIIb lymphoma. This open-label, randomized phase III trial compares two treatment approaches to understand whether Vitamin D affects outcomes in patients aged 65 and older undergoing immunochemotherapy. Participants are randomly assigned to one of two groups. Both groups receive a prephase of oral prednisone followed by six cycles of immunochemotherapy with R-CHOP or R-miniCHOP every 21 days. The experimental group also receives Vitamin D supplementation starting before treatment and continuing through immunochemotherapy according to a set schedule, including loading doses based on baseline Vitamin D levels and weekly maintenance. Patients may continue Vitamin D supplementation after treatment for up to two years. During the study, participants undergo baseline assessments and are monitored regularly through the treatment cycles. Researchers track progression-free survival over 54 months as the primary outcome, along with overall survival, response rates, Vitamin D levels, physical functioning, and fatigue. Safety and treatment adherence are also monitored, with follow-up visits extending up to several years to evaluate long-term outcomes.

Researchers are investigating Primary Cardiac Lymphoma PCL, a rare type of lymphoma that affects only the heart and sometimes the pericardium. This lymphoma accounts for a small portion of primary cardiac tumors and extranodal lymphomas and is more common in males. The most frequent form is Diffuse Large B Cell Lymphoma DLBCL, and while historically outcomes were poor, recent years have seen improved survival rates. The study aims to provide a detailed overview of PCL in Italy, addressing unknown aspects of the disease and its management to improve clinical practice. This observational study includes patients diagnosed with PCL from January 1, 2000, to December 31, 2020, who were treated with first-line chemoimmunotherapy regimens containing an anti-CD20 monoclonal antibody. The study collects information retrospectively to better understand treatment patterns, patient characteristics, and outcomes such as remission rates and survival. Participants data will be reviewed to evaluate overall survival, complete remission, response rates, progression-free survival, and incidences of central nervous system relapse. The study will also analyze the types of therapies given and their frequency. Data collection is expected to complete by late 2023, with outcomes assessed within two months thereafter. The study involves no active treatment or procedures for participants, focusing instead on gathering and analyzing existing clinical information.

Researchers are evaluating a new treatment approach for adults with newly diagnosed Acute Myeloid Leukemia AML who have mutations in the NPM1 or KMT2A genes and are not eligible for intensive chemotherapy. The study focuses on adding revumenib, a drug that blocks a molecule called menin important for leukemia cell survival, to standard treatment with azacitidine and venetoclax. This is a randomized, double-blind, placebo-controlled Phase 3 clinical trial aiming to improve outcomes for these patients. Participants will receive either revumenib or a placebo alongside azacitidine and venetoclax in continuous 28-day treatment cycles. Treatment continues until disease progression, unacceptable side effects, death, withdrawal, or other protocol-defined reasons for stopping. After the last patient is enrolled, there will be a 4-year follow-up period to observe survival and ongoing health. During the study, patients will be closely monitored with regular assessments to track overall survival, rates and duration of remission, event-free survival, and quality of life. Genetic and molecular tests will evaluate response at the bone marrow and blood levels. Safety and tolerability will also be monitored throughout treatment and the follow-up phase, which together may last several years.