Acute Leukemia

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 evaluating the side effects and best dose of a radioactive treatment called 211^astatine(At)-BC8-B10 in patients with high-risk acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or mixed-phenotype acute leukemia. This phase I/II trial studies how this targeted radioactive antibody might help kill cancer cells with less effect on healthy cells before patients undergo a donor stem cell transplant. The study is sponsored by a cancer center and aims to improve treatment outcomes for these serious blood cancers. Participants receive the 211^At-BC8-B10 treatment intravenously over 6 to 8 hours one week before their transplant. Some may also receive 131^I-BC8-B10 and fludarabine phosphate intravenously in the days leading up to transplant. On day 0, patients undergo total-body irradiation and a peripheral blood stem cell transplant. Following transplant, patients take cyclosporine and mycophenolate mofetil orally or intravenously on a schedule that varies depending on their donor type. The study includes possible imaging and sample collections such as SPECT scans, bone marrow aspirates, and blood tests. During the study, participants are closely monitored with various tests and evaluations to track side effects, treatment response, and transplant success. Researchers measure outcomes including serious toxicities within 100 days of transplant, engraftment of donor cells, graft-versus-host disease, remission rates, survival, and relapse over up to two years. Follow-up visits continue at 100 days, 6, 9, 12, 18, and 24 months after treatment to assess long-term effects and health.

Researchers are evaluating the side effects and optimal dose of a radioactive antibody agent called 211At-BC8-B10 in combination with donor stem cell transplant for patients with high-risk acute leukemia or myelodysplastic syndrome that has relapsed or is not responding to treatment. This phase I/II study aims to understand how 211At-BC8-B10, a monoclonal antibody that may affect cancer cell growth, works alongside chemotherapy, total body irradiation, and stem cell transplant to treat these conditions. Participants receive a preparative regimen including an infusion of 211At-BC8-B10 over 6 to 8 hours, followed by fludarabine and cyclophosphamide given intravenously on specific days, and total body irradiation before transplant. On transplant day, patients undergo peripheral blood stem cell or bone marrow transplant. After transplant, patients are given medications cyclophosphamide, mycophenolate mofetil, and tacrolimus to reduce the risk of graft versus host disease. They also receive granulocyte colony-stimulating factor until their white blood cell counts recover. During the study, participants have bone marrow biopsies, aspirations, and blood samples collected to monitor their condition. Follow-up visits occur at 100 days, and at 6, 9, 12, 18, and 24 months after treatment. Researchers measure outcomes such as serious toxic side effects, remission rates, engraftment success, donor cell presence, immune recovery, graft versus host disease, survival, and disease-free survival. The study is sponsored by the Fred Hutchinson Cancer Center and includes adults aged 18 to 75 years.

Researchers are evaluating a new combination treatment for patients with high-risk acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS). This phase I trial studies the safety, side effects, best dose, and potential effectiveness of a radioactive antibody called 225Ac-DOTA-Anti-CD38 daratumumab combined with chemotherapy drugs and targeted radiation as a conditioning treatment before donor stem cell transplant. The treatments aim to prepare the body to accept donor cells and target cancer cells more precisely. Participants receive daratumumab intravenously followed by related radioactive compounds early in the treatment process. They then undergo total marrow and lymphoid irradiation (TMLI) twice daily for several days, combined with chemotherapy drugs fludarabine and melphalan given intravenously. On day 0, patients receive a stem cell transplant, and preventive medications for graft-versus-host disease (GVHD) start before transplant. The study includes detailed imaging scans and biopsies before and during treatment to monitor effects. Throughout the trial, participants have regular evaluations including blood tests, bone marrow biopsies, heart and lung function tests, and various scans. After transplant, they are followed closely with frequent visits for the first 100 days, then less often up to two years to track side effects, transplant success, survival, and disease status. Researchers monitor adverse events, transplant-related complications, and overall outcomes to determine the best dose and safety of this new conditioning approach.

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 studying adult acute lymphoblastic leukemia (ALL), including its three main types: Ph-positive ALL, Ph-negative B-cell precursor ALL, and T-ALL/lymphoblastic 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-ALL/LL. 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 institution's 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 therapy's effects.

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.

Researchers are evaluating a new treatment called MK-1045 for people with precursor B-cell Acute Lymphoblastic Leukemia (B-ALL), a type of blood cancer that has returned after treatment or stopped responding to current therapies. The study has two parts: the first part focuses on finding the safe and best dose levels of MK-1045, while the second part aims to learn how well MK-1045 works to treat this condition. Adults in the dose escalation phase will receive weekly intravenous infusions of MK-1045 at doses ranging from 600 to 120,000 micrograms, given in treatment cycles of 4 weeks. Pediatric participants receive weight-based doses from 320 to 60,000 micrograms with the same weekly IV infusion schedule. Treatment cycles include 4 weeks of dosing followed by a 2-week break, with induction, consolidation, and maintenance phases depending on response and tolerance. Participants will be closely monitored throughout the study, with assessments for side effects, blood tests, and evaluations of cancer remission rates. Researchers will measure various outcomes such as adverse events, dose tolerability, complete remission rates, immune responses, and survival over periods ranging from weeks to up to 24 months. The study aims to understand both the safety and potential effectiveness of MK-1045 in treating precursor B-cell ALL.