B-Cell Malignancy

Multiple myeloma (MM) is a cancer of plasma cells that currently has no cure and often returns after treatment. Survival after diagnosis is typically 5 to 8 years. Researchers are evaluating whether the radiotracer 18F-fluciclovine, injected during PET/CT scans, is better at detecting MM than the commonly used 18F-FDG tracer, aiming to improve early detection and treatment decisions. This is a phase 2, open-label study involving adults with newly diagnosed or relapsed/refractory MM. Participants will receive an intravenous injection of 18F-fluciclovine (370 MBq) and undergo PET/CT scans at three key times: before treatment or early in treatment (newly diagnosed MM), six months after initial scans (relapsed/refractory MM), and either at disease progression or after 5 years. Each visit includes both 18F-fluciclovine and 18F-FDG PET/CT scans, an optional MRI, and a bone marrow biopsy from the hip. The study compares the effectiveness of these imaging methods in detecting MM. During the study, participants will have three visits for imaging and biopsies, with tests spread over about 30 days per visit. Blood tests, disease volume measurements, and bone marrow analysis will be performed to assess disease status and treatment response. Safety of 18F-fluciclovine will be monitored up to three days after each dose. Follow-up includes a final visit after 5 years or upon disease progression, allowing long-term monitoring of MM status.

Researchers are studying the use of 3'-deoxy-3'-[18F] fluorothymidine (FLT) positron emission tomography (PET) imaging in patients with cancer. This phase I trial aims to evaluate how well FLT PET imaging measures tumor growth and the activity of the DNA synthetic pathway in various cancers, including solid tumors and blood cancers. The study also seeks to determine how effective this imaging method is at detecting lesions and assessing response to treatment. Participants receive up to four FLT PET imaging procedures. During each procedure, a small amount of the FLT tracer compound is injected into the vein, followed by PET scan data collection for two hours to measure tumor growth. Blood samples may be taken during the scans, and urine samples collected afterward to analyze breakdown products of the tracer. Throughout the study, patients undergo assessments including PET or CT PET scans to measure tracer uptake and retention in tumors and normal organs. Researchers also evaluate changes in key enzymes related to DNA synthesis before and after therapy. These evaluations help monitor tumor activity and treatment response. The total time participants spend in the scanner during imaging is up to two hours per session, with a focus on capturing detailed tumor growth information.

Researchers are evaluating a new universal CAR T cell therapy called 4SCAR19U for patients with CD19-positive B cell malignancies. This phase I trial aims to assess the feasibility, safety, and effectiveness of these specially engineered T cells. The study also seeks to understand how well the 4SCAR19U T cells function and how long they remain active in patients. This approach may offer a faster, more cost-effective alternative to traditional CAR T therapies, especially for patients with weakened immune systems or rapidly progressing disease. The treatment involves infusing patients with universal CD19-specific CAR gene-engineered T cells known as 4SCAR19U cells. These cells are manufactured in bulk and ready to use off-the-shelf, avoiding the long preparation time required for patient-specific therapies. This immediate availability aims to provide timely treatment to patients who need it urgently. The trial is conducted at multiple clinical centers and includes one experimental group receiving the 4SCAR19U cell infusion. Participants will be monitored closely for safety over 24 weeks following the infusion, with evaluations of adverse effects and overall health. The study will also track the anti-tumor activity of the 4SCAR19U cells for up to one year after treatment. Assessments include physical exams, blood tests, and other clinical evaluations to understand the treatment's impact and cell persistence. The total duration of involvement varies, with long-term follow-up to gather important safety and effectiveness data.

Researchers are evaluating a new formulation of 64Cu-LLP2A, a drug used with PET/CT imaging, to study its dosimetry and imaging quality in healthy volunteers and patients with certain blood cancers. These cancers include multiple myeloma and various low-grade lymphomas. This early phase 1 study aims to confirm that the new formulation provides similar human dosimetry to previously published results and to expand evaluation to patients with confirmed diagnoses or those post bone marrow transplant with suspected recurrence. Participants will receive 64Cu-LLP2A followed by PET/CT imaging at up to three separate times depending on the injection day of the week. Imaging sessions involve multiple quick body scans within the first hour, additional scans between 120 to 240 minutes, and a later scan 15 to 28 hours post injection. Patients with known lesions will have dynamic imaging centered over those areas for one hour, plus an additional scan from head to upper thigh after injection. During the study, participants will undergo PET/CT scans and monitoring of organ dosimetry and safety for up to seven days after 64Cu-LLP2A administration. Researchers will assess the quality of PET images by looking at bone marrow uptake and tumor-to-background ratios. Safety will be tracked by recording any adverse events. The total imaging and evaluation period is estimated to last up to two days, with additional follow-up phone assessments.

Researchers are studying the use of [90Y]Y-PentixaTher ([90Y]Y-PTT) to treat patients with recurrent or refractory primary or isolated secondary central nervous system (CNS) lymphoma. This open-label, single-arm phase 1/2 study aims to evaluate the safety, tolerability, biodistribution, and preliminary effectiveness of this treatment. The study includes three dose-level groups, and a safety review committee will carefully monitor for any dose-limiting side effects to guide dose adjustments. Participants will receive one cycle of [90Y]Y-PTT administered intravenously. The study follows a best-of-5 dose escalation design across three cohorts with different dose levels. There is no comparison group in this study. After the treatment, patients will undergo several visits during the core study phase to assess safety, how the drug spreads in the body, dosimetry, and treatment response. Following this, three follow-up visits will occur at three-month intervals to monitor disease status. Throughout the study, participants will be closely monitored for adverse events, with severity graded by standard criteria. Various imaging and laboratory tests will be performed shortly after infusion and at multiple time points to measure drug uptake in tumors and organs, blood levels, and absorbed radiation doses. Researchers will assess response rates, progression-free survival, and overall survival at one, three, six, nine, and twelve months after treatment. The total study duration includes screening, treatment, core evaluations, and extended follow-up visits to comprehensively evaluate treatment outcomes and safety.

This observational study aims to create a national registry in Italy for multiple myeloma to monitor routine clinical practice and describe the standard care used for diagnosis and treatment. Multiple myeloma accounts for a small percentage of tumor diagnoses in Italy, with incidence rates of 9.5 per 100,000 males and 8.1 per 100,000 females. The registry will help analyze current treatment patterns and patient demographics to address future changes in care. The study involves a non-interventional, multicenter registry collecting both retrospective and prospective data from patients diagnosed with multiple myeloma since January 1, 2019. Data will be gathered using an electronic platform, and patients will be enrolled consecutively during their regular appointments after providing informed consent. Patients participating in other studies can also be included, with baseline and survival data collected for those in interventional trials. Participants will have hospital visits every six months, where clinical data and patient-reported outcomes will be recorded. Researchers will assess overall survival and time to next treatment over three years, along with patient-reported outcomes and costs incurred by patients. The study provides long-term monitoring without altering patients' usual care, and participation duration may vary depending on individual follow-up.

Researchers are evaluating the safety and effectiveness of BCMA-targeted prime CAR-T cell therapy in patients with relapsed or refractory Multiple Myeloma and other plasma cell diseases. This study focuses on patients who have limited treatment options and aims to assess adverse events and disease response after receiving this targeted therapy. Participants will receive a single treatment of BCMA-targeted prime CAR-T cells designed to attack myeloma cells expressing BCMA. The study includes Phase 1 and Phase 2 components and monitors patients for up to two years to evaluate treatment response and safety. During the study, participants will undergo regular assessments including monitoring of adverse events, disease status, levels of BCMA-targeted CAR-T cells in blood and bone marrow, clonal plasma cell quantities, serum IL-6 levels, and survival outcomes. The total follow-up duration for outcome measurement is up to two years to observe treatment effects and patient safety over time.

Researchers are evaluating the effectiveness and safety of CD19 and CD22 targeted prime CAR-T cell therapy for patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). This study addresses patients who have not responded to previous anti-CD19 CAR-T treatments or who have experienced relapse without CD19 expression. The goal is to improve outcomes for these patients using a new targeted CAR-T cell approach. Participants will receive a single intravenous infusion of CD19 and CD22 targeted prime CAR-T cells as the experimental treatment. This single-arm study involves no placebo or comparison group. The therapy targets both CD19 and CD22 proteins on leukemia cells to potentially overcome resistance seen with prior treatments. During the study, participants will be closely monitored for adverse events related to the treatment for up to two years. Researchers will assess the response rate to the CAR-T therapy over six months and track various measures such as CAR-T cell presence in bone marrow and blood, immune factors like IL-6 and TNF-alpha, and survival outcomes. Patients will have regular visits and evaluations to ensure safety and to collect data on the therapy's effects.

Researchers are evaluating TQB2934, a special antibody designed to target multiple myeloma, a cancer affecting plasma cells. This antibody binds to T cells and cancer cells to activate the immune system to attack the disease. The study is a Phase 1 clinical trial focusing on safety and the body's handling of the drug in patients with malignant plasma cell tumors. The study involves giving TQB2934 as a subcutaneous injection at doses of 40mg or 60mg. Treatment cycles occur once weekly during the first three cycles, then every two weeks for cycles four to six. If patients achieve a partial remission or better after six cycles, dosing continues every four weeks. Each treatment cycle lasts 28 days. Participants will undergo various assessments including blood tests to measure drug levels and immune response over 120 hours after each dose. Researchers will monitor adverse events for up to 24 months and evaluate treatment responses such as remission rates and survival outcomes. The total study participation includes treatment and long-term safety follow-up lasting up to two years.

Researchers are evaluating the safety and effectiveness of GT801 injection in adult patients with relapsed or refractory CD19-positive B-cell blood cancers and autoimmune hemolytic anemia. This early phase 1 clinical study focuses on patients with B-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, B-cell non-Hodgkin's lymphoma, and autoimmune hemolytic anemia who have experienced disease progression after at least second-line drug treatments. The study includes an interim analysis after two patients complete the primary endpoint measurement. Participants will receive GT801 injection as the experimental treatment. The study monitors the proportion of participants experiencing dose-limiting toxicities within 28 days and tracks adverse events for three months after infusion. Additionally, secondary outcomes such as overall response rates, duration of response, progression-free survival, and overall survival up to 12 months post-infusion are assessed for hematologic malignancies. For autoimmune hemolytic anemia, response rates, disease-free recurrence, and time to response are also measured over 12 months. During the study, participants will be closely monitored through clinical assessments and safety evaluations, including adverse event tracking for three months and disease response assessments for up to one year. The study requires participants to meet specific eligibility criteria, including confirmed CD19 positivity and prior treatment history. Follow-up evaluations will ensure ongoing safety and measure treatment outcomes, with participation lasting up to 12 months after GT801 infusion.