Acute Lymphoblastic Leukemia (ALL)

This research aims to investigate adult patients with triple negative B-cell Acute Lymphoblastic Leukemia B-ALL who do not have the most common genetic rearrangements linked to the disease. These patients often have a poor prognosis and lack targeted therapies. The study focuses on understanding the molecular characteristics of this subgroup, especially regarding CRLF2 gene alterations, which are important in both adult and pediatric cases and may influence treatment outcomes. The study is non-interventional and observational, meaning treatment decisions are made by doctors as usual and are not influenced by participation. Patients diagnosed with primary or secondary B-ALL will be enrolled and their blood, bone marrow, and saliva samples collected for detailed biological analysis using various laboratory techniques, including gene sequencing and flow cytometry. Both prospective and retrospective patient groups will be studied over a planned period of 36 months. Participants will provide biological samples and clinical data, which will be recorded in a dedicated database. Researchers will evaluate molecular markers to identify patient subgroups, assess potential biomarkers, and correlate findings with survival outcomes. The study aims to develop a rapid and cost-effective method for identifying these leukemia subtypes, with ongoing monitoring and data collection continuing throughout the three-year study duration.

Researchers are studying the use of 211astatineAt-BC8-B10, a radioactive substance linked to a monoclonal antibody, in patients with high-risk acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or mixed-phenotype acute leukemia. The trial is a phase III dose-escalation study focused on evaluating side effects and determining the best dose before patients undergo donor stem cell transplant. This approach aims to target cancer cells with radiation while minimizing effects on healthy cells. Participants receive 211At-BC8-B10 intravenously over 6 to 8 hours on day -7 and may also receive 131I-BC8-B10 on the same day. They receive fludarabine phosphate intravenously on days -4, -3, and -2, followed by total-body irradiation and peripheral blood stem cell transplant on day 0. Patients take cyclosporine orally or intravenously every 12 hours from days -3 to 56, with tapering schedules depending on donor type, and mycophenolate mofetil orally or intravenously starting shortly after transplant with dosing adjustments over time. Some participants may have imaging scans, bone marrow aspirate, and blood samples collected during the study. Throughout the study, patients are closely monitored for treatment effects and side effects, including dose-limiting toxicities up to 30 days post-transplant and veno-occlusive disease up to 60 days. Additional outcomes include engraftment, chimerism, graft versus host disease, remission status, and survival tracked up to two years. Follow-up visits occur at 100 days, then 6, 9, 12, 18, and 24 months after treatment to assess recovery and long-term effects.

Researchers are evaluating a radioactive agent linked to an antibody called 211At-BC8-B10 followed by donor stem cell transplant for patients with high-risk acute leukemia or myelodysplastic syndrome that has returned or is not responding to treatment. This phase III trial studies the side effects and best dose of this treatment. The antibody may interfere with cancer cell growth, and the transplant aims to help the patients bone marrow produce healthy blood cells. Additional medications are given to help prevent complications like graft versus host disease. Participants receive a preparative regimen including an infusion of 211At-BC8-B10 over 6-8 hours on day -8, followed by chemotherapy drugs fludarabine and cyclophosphamide over several days. Total-body irradiation TBI is given on day -1. On day 0, patients undergo peripheral blood stem cell or bone marrow transplant. After transplant, patients receive medications cyclophosphamide, mycophenolate mofetil, and tacrolimus to reduce the risk of graft versus host disease. Granulocyte colony-stimulating factor G-CSF is started on day 5 to support white blood cell recovery. Throughout the study, patients undergo bone marrow biopsies, aspirations, and blood sample collections. They are followed up at day 100 and then at 6, 9, 12, 18, and 24 months after treatment. Researchers monitor side effects including dose-limiting toxicities, remission rates, engraftment success, donor chimerism, immune recovery, graft versus host disease, survival, and disease-free survival. Patient health and safety are regularly assessed during and after treatment.

Researchers are evaluating the safety, side effects, best dose, and effectiveness of a combination conditioning treatment for donor stem cell transplantation in patients with high-risk acute myeloid leukemia AML, acute lymphoblastic leukemia ALL, and myelodysplastic syndrome MDS. This phase I trial studies a targeted radioimmunotherapy drug, 225Ac-DOTA-Anti-CD38 daratumumab, combined with chemotherapy drugs fludarabine and melphalan, and total marrow and lymphoid irradiation TMLI. Daratumumab targets CD38 on cancer and immune cells, potentially helping the immune system to attack cancer cells. Participants receive daratumumab intravenously followed by indium In 111-DOTA-daratumumab and actinium Ac 225-DOTA-daratumumab on day -15. Total marrow and lymphoid irradiation is given twice daily from days -8 to -5, fludarabine is given intravenously on days -4 to -2, and melphalan on day -2. On day 0, participants undergo hematopoietic cell transplantation HCT. Graft-versus-host disease GVHD prevention with sirolimus and tacrolimus starts on day -1. Throughout the study, participants undergo various scans, biopsies, and blood tests to monitor treatment effects and safety. Participants are monitored closely after transplantation with visits twice weekly for the first 100 days, then twice monthly up to six months, and monthly thereafter until immunosuppressive therapy is stopped without GVHD signs. Yearly follow-up continues for two years. Assessments include adverse events, survival rates, relapse, graft-versus-host disease incidence, infections, blood cell recovery, organ function, and drug distribution. The study aims to determine the maximum tolerated dose and evaluate overall safety and effectiveness of the treatment combination.

Researchers are studying adult acute lymphoblastic leukemia ALL, including its three main types Ph-positive ALL, Ph-negative B-cell precursor ALL, and T-ALLlymphoblastic lymphoma. The study aims to improve frontline treatment outcomes by incorporating new antibody-based therapies and refining when allogeneic hematopoietic stem cell transplantation HSCT is needed in first remission. Current treatments have improved survival but there is still potential for better results, especially by reducing relapse and improving survival with new immunotherapies. The trial is a prospective, multicenter, multi-country randomized study with three cohorts based on ALL subtype Ph-negative BCP-ALL, Ph-positive ALL, and T-ALLLL. Treatments include standard chemotherapy, blinatumomab an anti-CD19 antibody, ponatinib a tyrosine kinase inhibitor, and isatuximab an anti-CD38 antibody depending on the cohort. Some participants receive HSCT as standard care. These treatments are given in cycles with specific dosing schedules, including intravenous infusions and oral medications, from induction through maintenance phases. Participants will be closely monitored through scheduled visits involving blood tests, measurable residual disease assessments, physical exams, and questionnaires to track treatment effects and safety. Researchers will measure outcomes such as overall survival, event-free survival, relapse rates, and quality of life over a period of up to five years. Safety and adverse events will also be recorded, with ongoing assessments to evaluate how well the new therapies work and their impact on participants health.

Researchers are evaluating the effectiveness of a six-month virtually-delivered dietary education program called PEDALL to prevent overweight and obesity during maintenance chemotherapy in children and adolescents with acute lymphoblastic leukemia ALL. The study focuses on English and Spanish speaking families and considers key genetic and sociodemographic risk factors that may affect weight gain during treatment. Participants will be randomly assigned to one of two groups the PEDALL intervention group or the standard of care SOC group. The PEDALL group will receive 26 contact hours of specialized nutrition education through weekly one-hour virtual sessions over six months. The SOC group will receive printed educational materials and nutritional care according to their institutions usual practices. During the study, participants and their caregivers will engage in nutrition education and counseling sessions. Researchers will assess weight status, body mass index trajectories, lifestyle behaviors, and the influence of genetic and sociodemographic factors over time. The main goal is to prevent unhealthy weight gain during maintenance chemotherapy and improve long-term health outcomes for childhood ALL survivors. The study will last up to 3.5 years for primary outcomes, with additional follow-up extending to four years.

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 therapys effects.

Researchers are studying the safety and effectiveness of GT801 injection in adults who have relapsed or refractory CD19-positive B-cell blood cancers, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, non-Hodgkins lymphoma, and autoimmune hemolytic anemia. This early phase 1 study aims to understand how well the treatment works and its side effects in this group of patients. Participants will receive the GT801 injection as the study treatment. The study focuses on one group receiving this intervention. The treatment schedule and dosing details are not specified, but safety and response to the treatment will be monitored over a period of time, including up to 12 months after infusion. During the study, participants will be closely monitored for side effects and treatment responses through various assessments. Researchers will measure the proportion of participants experiencing dose-limiting toxicity within 28 days and track adverse events up to 3 months after infusion. They will also evaluate overall response rates, duration of response, progression-free survival, and other outcome measures related to both the blood cancers and autoimmune hemolytic anemia for up to 12 months. The study includes regular follow-up visits and evaluations to gather this information.

Researchers are studying a new treatment called MK-1045 for people with precursor B-cell Acute Lymphoblastic Leukemia B-ALL that has returned after treatment or stopped responding to current therapies. This trial includes two parts a dose escalation phase to find the safest and most effective dose, and a Phase II part to evaluate how well MK-1045 works. The study focuses on safety, tolerability, and treatment response in both adults and children aged 2 years and older. In the dose escalation phase, adults receive MK-1045 doses ranging from 600 to 120,000 micrograms once weekly through intravenous infusion in treatment cycles of 4 weeks. Pediatric patients receive weight-based doses from 320 to 60,000 micrograms on the same weekly schedule. Treatment starts with induction cycles, followed by consolidation and maintenance phases, continuing until certain conditions such as disease progression or intolerable toxicity occur. The study is open-label and non-randomized, assessing MK-1045 administered intravenously over multiple treatment cycles. Participants will have their health closely monitored with regular assessments including adverse event tracking, blood tests, and evaluations of leukemia response. Researchers will measure outcomes such as remission rates, drug levels in the blood, immune cell activity, and survival over periods up to two years. The trial includes both adult and pediatric participants and aims to gather detailed safety and effectiveness data throughout treatment and follow-up periods.

Researchers are evaluating SCTC21C, a biological treatment, in patients with relapsed or refractory CD38-positive hematologic malignancies. This multicenter, open-label Phase I trial aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, preliminary anti-tumor activity, and immune response to SCTC21C. The study includes a dose-finding stage to determine safe dosage levels and a dose-expansion stage to further evaluate selected doses. In the dose-finding stage, participants receive increasing doses of SCTC21C ranging from 0.01 mg up to 960 mg. In the dose-expansion stage, at least 20 participants are randomly assigned in a 11 ratio to receive two different doses determined from the earlier stage. SCTC21C is given by subcutaneous injection weekly for the first two cycles, then every two weeks for cycles three to six, and every four weeks thereafter until disease progression or unacceptable side effects occur. Participants will be closely monitored throughout the study with assessments including safety evaluations, adverse event tracking up to 45 days after the last dose, and measuring dose-limiting toxicities during the first 28-day cycle. Researchers will also evaluate tumor response over about one year of treatment. The study expects participants to have regular visits for treatment and monitoring, with the total duration varying depending on individual response and tolerability.