Clinical Research Directory

Axatilimab + CAR-T for High-Risk Lymphoma

Axatilimab + CAR-T in High-Risk Lymphoma

Prospective ctDNA Testing in Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) are aggressive lymphomas commonly treated with first-line immunochemotherapy. Some patients experience disease progression or relapse despite treatment. PET/CT is used to assess treatment response, but it may not identify small amounts of residual lymphoma. Circulating tumor DNA (ctDNA) consists of tumor-derived DNA fragments detectable in blood. This prospective observational study will use PhasED-seq to assess plasma ctDNA before, during, and after first-line therapy in approximately 100 patients with newly diagnosed DLBCL or HGBL. The primary objective is to evaluate the association between ctDNA status approximately 8 weeks after completion of first-line therapy and subsequent progression-free survival. Additional analyses will examine overall survival, earlier ctDNA findings, and baseline tumor molecular subtypes. PET/CT findings will provide complementary information for exploratory analyses. The findings may inform future studies of response-adapted treatment.

Prizloncabtagene Autoleucel (Prizlon-cel) for the Treatment of Relapsed or Refractory Large B-cell Lymphoma Post FDA Approved CAR T-cell Therapy

This Phase 2, multicenter, open-label study will evaluate the safety and efficacy of a single infusion of Prizloncel, an anti-CD19/CD20 chimeric antigen receptor T cells following lymphodepleting chemotherapy in participants with relapsed/refractory (r/r) diffuse large B-cell lymphoma post FDA approved, commercially available CAR T-cell therapy Approximately 50 participants will undergo leukapheresis, lymphodepletion with fludarabine and cyclophosphamide, and infusion of Prizlon-cel. Participants will be followed for 24 months (approximately 2 years) to evaluate efficacy, safety, CAR T-cell persistence, pharmacokinetics/pharmacodynamics, and biomarkers. Long-term safety follow-up for gene therapy-related events will continue for up to 15 years following CAR T-cell infusion.

A Phase 1/2 Study of UB-VV400 With Rapamycin in Relapsed/Refractory B-cell Malignancies

This study is a Phase 1/2 dose-finding and dose-confirmation study to evaluate the safety and antitumor activity of UB-VV400. The study will enroll patients with relapsed/refractory B-cell malignancies, including large B-cell lymphoma (LBCL).

CD19.20.22 CAR T-cells for Patients With Relapsed/Refractory B-Cell Lymphomas

The goal of this study is to treat patients diagnosed with relapsed or refractory positive B cell lymphoma - positive for 2 or more target antigens - with CAR19.20.22 CAR T-cells. Based on the preclinical characteristics of the LTG2950, CAR19.20.22 tri-specific CAR T-cells the Investigators have developed the following hypotheses to be tested in our phase Ia clinical trial. The Investigators hypothesize that these novel CAR T-cells will show: * good safety and tolerability * a high degree of efficacy * very good persistence * an acceptable level of exhaustion

Proton Therapy for Mediastinal Lymphoma (PROMLY)

The study aims to investigate whether proton therapy is feasible in a national setting and whether proton therapy can reduce the risk of late toxicity (secondary cancers and heart toxicity) compared to foton therapy.

Lifestyles Implemented-Survivorship Care Plan In Lymphoma Survivors

This is a prospective randomized open-label, multicenter, 2-arm study to assess the role of healthy LifeStyle implemented Survivorship Care Plan (LS-SCP) in modifying the Quality of Life (QoL) in a population of long-term lymphoma survivors (in remission for a minimum 3 years since the last treatment and a maximum of 10 years).

Mosunetuzumab and Polatuzumab Vedotin With Split-Dose CHP Chemotherapy for Elderly Patients With Diffuse Large B-Cell Lymphoma

This single-arm, interventional phase 2 study is designed to evaluate whether the inclusion of mosunetuzumab subcutaneous and polatuzumab vedotin (Mosun-Pola) to a split-dose CHP chemotherapy backbone will improve outcomes for elderly patients with a new diagnosis of diffuse large B-cell lymphoma.

GRACE: A Phase 1/2a Study of VTRU200 in Relapsed/Refractory AML, High-risk MDS, DLBCL Post CART Failure and Advanced Solid Tumors

About this study This is the first study of VTRU200 in people. The main purpose of this study is to find a safe dose of VTRU200 and learn how the medicine behaves in the body. Researchers will also look for early signs that it may help treat cancer. VTRU200 is an experimental immunotherapy. It is designed to help the body's immune system find and destroy cancer cells while limiting effects on healthy cells. Unlike many cancer treatments that target a single protein, VTRU200 recognizes stress signals that are commonly found on cancer cells. These signals include certain sugars (called glycans) and fats (called phospholipids) that are present on many types of cancer cells but are uncommon on normal healthy cells. VTRU200 also attaches to immune cells called T cells and helps direct them to attack cancer cells. Because VTRU200 targets features that are shared by many cancers, it may continue to work even if cancer cells lose or change individual proteins that other treatments depend on. Who can take part? This study is for people with certain blood cancers that have come back after treatment or have not responded to available treatments. These include: Acute myeloid leukemia (AML) Higher-risk myelodysplastic syndromes (HR-MDS) Diffuse large B-cell lymphoma (DLBCL) that has returned after CAR T-cell therapy Later parts of the study may also include adolescents and children with AML. What will happen during the study? Participants will receive VTRU200 through a vein (intravenous infusion). The study will begin by giving small doses to help determine the safest dose for future participants. If those doses are well tolerated, later participants may receive higher doses. Researchers will: Monitor participants closely for side effects. Perform blood tests to measure how VTRU200 moves through and leaves the body. Measure how the immune system responds to treatment. Check whether the cancer shrinks, disappears, or remains under control. Participants may receive multiple treatment cycles if they continue to benefit and do not have unacceptable side effects. What are the possible benefits? VTRU200 may or may not help participants. Information learned from this study may help develop new treatments for people with these cancers in the future. What are the possible risks? Because VTRU200 is being tested in humans for the first time, not all side effects are known. Possible risks include reactions related to activation of the immune system, infusion-related reactions, laboratory test changes, and other side effects. Participants will be monitored closely throughout the study, and medical care will be available if side effects occur. Brief Study Description This first-in-human, open-label, Phase 1/2a study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary antitumor activity of VTRU200 in participants with relapsed or refractory acute myeloid leukemia (AML), higher-risk myelodysplastic syndromes (HR-MDS), or diffuse large B-cell lymphoma (DLBCL) following CAR T-cell therapy. VTRU200 is an investigational trispecific T-cell engager that binds stress-associated glycans, phosphatidylserine, and CD3 to redirect T cells toward cancer cells. The Phase 1 dose-escalation portion will determine the recommended Phase 2 dose (RP2D), followed by disease-specific expansion cohorts to further evaluate safety and preliminary antitumor activity. Why is this research important? Many blood cancers eventually stop responding to available treatments. Cancer cells can escape therapy by changing or losing the proteins that many current medicines target. VTRU200 is designed to recognize stress-related features that many cancer cells share rather than relying on a single protein target. Researchers hope this approach may reduce the chance of treatment resistance while limiting damage to healthy cells. This study will help determine whether VTRU200 can be given safely and whether it shows early signs of helping people with difficult-to-treat blood cancers.

A Study to Investigate Ronde-cel Versus Investigator's Choice CD19 CAR T-Cell Therapy

This Phase 3 study compares rondecabtagene autoleucel (ronde-cel), a dual-targeting CD19/CD20 CAR T-cell therapy, with investigator's choice of CD19 CAR T-cell therapy in patients with relapsed or refractory large B-cell lymphoma in the second-line setting.

A Study of Glofitamab-based Treatment in People With Diffuse Large B-cell Lymphoma

The researchers are doing this study to find out if the study treatment is an effective treatment that causes few or mild side effects in people with diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBCL), or transformed lymphoma. The treatment being tested in this study is glofitamab, polatuzumab, and obinutuzumab in combination with standard treatment (the combination of rituximab, cyclophosphamide, doxorubicin, and prednisone, or R-miniCHP).

A Phase II Study to Evaluate the Efficacy of UF-KURE19 Cells in Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphomas

The goal of this Phase II single-arm, open-label clinical trial is to evaluate whether UF-KURE19, an autologous CD19-directed CAR-T cell therapy manufactured t…The goal of this Phase II single-arm, open-label clinical trial is to evaluate whether UF-KURE19, an autologous CD19-directed CAR-T cell therapy manufactured through an ultra-fast (less than 1 day) process, can treat adult patients (18 years and older, male or female) with relapsed or refractory B-cell Non-Hodgkin Lymphoma (NHL), including Large B-Cell Lymphoma (LBCL), Follicular Lymphoma (FL), and Marginal Zone Lymphoma (MZL). The participants will be divided in two cohorts: 81 participants in Cohort 1: Large B-Cell Lymphoma (LBCL) 24 participants in Cohort 2: Follicular Lymphoma (FC) and Marginal Zone Lymphoma (MZL) The main questions it aims to answer are: 1. Can UF-KURE19 achieve a clinically meaningful complete response rate (CRR) of ≥ 45% in patients with relapsed/refractory LBCL at Day 90 post-infusion, per Lugano Revised Response Criteria? 2. Can UF-KURE19 achieve a CRR of ≥ 60% in patients with relapsed/refractory Follicular or Marginal Zone Lymphoma at Day 90 post-infusion? There is no comparison group. This is a single-arm study, (all participants receive UF-KURE19) with 2 cohorts as outlined above. Participants will: 1. Undergo leukapheresis for collection of their own T cells, which will be used to manufacture UF-KURE19. 2. Subsequently they will receive a single intravenous infusion of UF-KURE19 (10×10⁶ cells for patients ≥50kg; 7×10⁶ cells for patients \<50kg) Complete disease response assessments at Day 90 post-infusion per Lugano criteria 3. Undergo safety monitoring including adverse event collection, laboratory tests, neurological exams, CAR-T persistence assays, and replication-competent lentivirus (RCL) testing throughout the study 4. Be followed long-term for up to 15 years post-infusion for gene therapy safety surveillance per FDA requirements

A Study of Glofitamab Plus GemOx Compared With Standard of Care in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

The purpose of this study is to evaluate the efficacy and safety of glofitamab in combination with gemcitabine plus oxaliplatin (GemOx) versus standard of care (SOC) in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who have relapsed early (within 1 year) or are primary refractory to first-line therapy. Participants will be randomly assigned in a 1:1 ratio to receive either the Glofitamab-GemOx combination regimen or SOC. The SOC arm consists of investigator's choice of salvage chemoimmunotherapy followed by autologous stem cell transplantation (ASCT) for eligible patients. The primary endpoint of the study is event-free survival (EFS).

A Study of NX-5948 in Adults With Relapsed/Refractory B-cell Malignancies

This is a first-in-human Phase 1a/1b multicenter, open-label study designed to evaluate the safety and anti-cancer activity of NX-5948 in patients with advanced B-cell malignancies.

Radiation, Oral Vancomycin, and CAR-T for B-Cell Lymphomas

This clinical trial assesses whether it is feasible to use radiation therapy with vancomycin prior to CAR T-cell therapy for patients with large B-cell lymphomas

Neurocognitive Assessment in Long-Term Survivors of Lymphoma

This is an observational, multicenter, prospective cohort study including patients treated for lymphoma in Italian real-life. Patients eligible for the enrollment in the study will be consecutively included in Italian FIL centers. Patients will be evaluated once during regular follow-up, in the absence of clinical or radiologic signs of disease relapse. The assessment of neurocognitive functioning will be performed through a panel of tests, both self-administered and individually administered (about 1 hour). The administration of these neuropsychological tests should be done according to a standardized and predefined order. If available, according to local practice, a neuropsychologist may be involved in test administration and in the evaluation of the results. Based on its observational nature, no treatment change or modification or additional exams or visits will be required because of being enrolled in this study.

GEN3014 Trial in Relapsed or Refractory Hematologic Malignancies

The drug that will be investigated in the study is an antibody, GEN3014. Since this is the first study of GEN3014 in humans, the main purpose is to evaluate safety. In addition to safety, the study will determine the recommended GEN3014 dose to be tested in a larger group of participants and assess preliminary clinical activity of GEN3014. GEN3014 will be studied in relapsed (disease has returned) or refractory (resistant to treatment) multiple myeloma (also known as RRMM) and other blood cancers. The study consists of 3 parts: 1. The Dose Escalation will test increasing doses of GEN3014 to identify a safe dose level to be tested in the other two parts. 2. Expansion Part A will further test the GEN3014 dose determined from the Dose Escalation. 3. Expansion Part B will compare intravenous (IV) GEN3014 with the subcutaneous (SC) daratumumab in ex-US countries. Participants will receive either GEN3014 into the vein or daratumumab under the skin; none will be given placebo. The study duration will be different for the individual participants. Overall, the study may be ongoing up to 5 years after the last participant's first treatment.

Multicenter Retrospective Observational Study of Relapsed Diffuse Large B-Cell Lymphoma Presenting as Indolent Lymphoma

Most relapses of diffuse large B-cell lymphoma (DLBCL) occur as high-grade lymphoma within the first two years after diagnosis. Relapses as indolent lymphoma are rare events, and the true incidence of this phenomenon is unknown, since literature data are scarce/ and usually restricted to case reports. Analogously, reported treatment strategies are rather heterogeneous, since no standard of care is established and advanced age together with previous anthracycline exposure may narrow the therapeutic choice. The goal of this observational study is to assess epidemiological, clinical characteristics and survival of diffuse large b-cell lymphoma (DLBCL) relapsing as indolent lymphoma. More precisely, the study aims at identifying diagnostic and imaging features associated with relapse as indolent lymphoma and at evaluating disease response to selected therapies.

Bio-CAR-T BS Study

The aim of this Study is the evaluation of post-infusion CAR-T (Chimeric Antigen Receptor T Cell) expansion and persistence in patients with DLBCL, PMBCL and ALL undergoing CAR-T therapy; and the feasibility and efficacy of the treatment in the real life practice.

Feasibility Trial of Glofitamab in a Response Adapted Approach Incorporating Interim FDG PET and ctDNA to Optimize Primary Therapy of DLBCL (GRAIL)

This is a phase ll study of participants with untreated diffuse large B Cell lymphoma (DLBCL).

Pomalidomide, Anti-PD-1 Antibody Combined With Selinexor (PPS) in Relapsed/Refractory Primary Central Nervous System Diffuse Large B-Cell Lymphoma

Primary central nervous system diffuse large B-cell lymphoma (PCNSL-DLBCL) is a highly aggressive malignancy accounting for over 80% of primary CNS lymphomas, with an annual incidence of 0.4-0.6 per 100,000 people globally and a rising trend in immunocompetent patients. First-line high-dose methotrexate-based chemotherapy causes severe toxicities and nearly 50% of patients relapse within 1-2 years, developing relapsed/refractory (R/R) disease. Treatment options for R/R PCNSL are scarce, with low response rates, median survival of only 3-6 months, and 5-year survival below 5%. The blood-brain barrier and tumor heterogeneity further worsen outcomes. This prospective, multicenter, single-arm phase II study evaluates the efficacy and safety of pomalidomide, PD-1 inhibitor, and selinexor (PPS) in R/R PCNSL, aiming to provide a new effective treatment.

KSV01 Injection for the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma

This is a single center, single arm, open-label, dose escalation, phase 1 study to evaluate the safety, tolerability and preliminary efficacy of KSV01 Injection for patients with diffuse large B-cell lymphoma.

Neurocognitive Assessment in Adults Undergoing CD19 Targeted CAR-T Cell Therapy

This is an observational, multicenter, prospective cohort study including patients treated with CAR-T in Italian centers. Patients eligible for enrollment in the study will be consecutively included in Italian FIL centers. A longitudinal survey will be carried out by collecting patients' data before starting CAR-T (T0) and after 6 (T1), 12 (T2) and 24 (T3) months after CAR-T infusion.

Lisatoclax Plus R-CHOP or Pola-R-CHP in Untreated DLBCL: A Phase Ib/II Study

This is a prospective, multicenter, open-label Phase Ib/II clinical study designed to evaluate the safety, tolerability, preliminary efficacy, and pharmacokinetics of lisatoclax in combination with R-CHOP or Pola-R-CHP in patients with previously untreated diffuse large B-cell lymphoma (DLBCL).