Myelodysplastic Syndrome (MDS)

Researchers are evaluating the use of 18F-Pentixafor PET imaging to improve the diagnosis, staging, and response evaluation of hematological malignancies such as multiple myeloma, leukemia, and lymphoma. This imaging method targets the CXCR-4 receptor, which is overexpressed in these tumors and is linked to tumor growth and poor prognosis. The study aims to assess how well 18F-Pentixafor PET performs compared to current imaging methods like 18F-FDG PET. Participants will receive a single intravenous injection of 18F-Pentixafor at a dose of 55 MBq/kg. After 60 minutes, they will undergo either a PET/CT or PET/MR scan. This process allows for detailed imaging without special preparation. The study includes patients with suspected or confirmed hematological malignancies and involves only one imaging session per participant. During the study, researchers will monitor diagnostic accuracy and compare 18F-Pentixafor PET's performance with traditional 18F-FDG PET imaging. They will also assess disease activity using the Deauville Score over a period of up to 3-4 years. Participants will be involved in imaging procedures and may undergo biopsies if needed for diagnosis. The study will continue until December 2029, with an average follow-up of about 1.5 years for primary outcome assessment.

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.

Myelodysplastic syndrome (MDS), also called bone marrow failure, is a condition where the bone marrow produces fewer blood cells due to abnormal cell development. This study evaluates a new approach to treating MDS by using an alternating low-dose schedule of two chemotherapy drugs, 5-azacitidine (5AZA) and decitabine (DEC), to overcome resistance that can occur when either drug is given alone. The study is an early phase 1 pilot trial focusing on this combined treatment for myeloid malignancies including MDS and related disorders. Participants will receive 5AZA and DEC in a weekly alternating schedule: 5AZA at 50 mg/m² on Day 1 and DEC at 5 mg/m² on Day 4 each week. The first 8 weeks serve as an induction phase, followed by a long-term treatment phase starting from week 9. Treatment will continue for at least 24 weeks unless the disease progresses. Those who respond to therapy may continue treatment until relapse or disease progression not responsive to dose escalation. During the trial, participants will be regularly monitored for response using criteria including complete or partial response and hematologic improvement. Safety will be assessed by tracking adverse events. The study also explores biological markers related to treatment response. Participants may remain in the study for up to 6 months after treatment to assess overall response, with some outcomes followed for up to 2 years. Careful evaluation of blood counts, disease status, and side effects will guide treatment continuation and study assessments.

Researchers are conducting a Phase 1, open-label, multicenter clinical study to evaluate the safety, pharmacokinetics, and preliminary efficacy of HMPL-506 in patients with hematological malignancies. The study focuses on patients with specific genetic alterations in blood cancers, including relapsed or refractory Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), and multiple myeloma (MM). The trial is sponsored by Hutchmed and aims to enroll between 60 and 132 patients across two phases: dose escalation and dose expansion. In the dose escalation phase, approximately 30 to 38 patients with MLL-rearranged and/or NPM1-mutant relapsed/refractory AML or ALL will receive escalating oral doses of HMPL-506 once daily. Starting at 50 mg, doses may increase based on safety, efficacy, and pharmacokinetic data, with adjustments guided by a Safety Monitoring Committee. The dose expansion phase will enroll about 30 to 60 patients divided into three cohorts based on specific genetic markers or disease type. Patients in this phase will receive the recommended phase 2 dose in 28-day cycles until disease progression, unacceptable toxicity, or other study endpoints. Participants will undergo regular assessments including bone marrow aspiration and biopsy, safety monitoring for dose-limiting toxicities and adverse events, and evaluations of anti-tumor efficacy every treatment cycle. Pharmacokinetic and pharmacodynamic analyses will be conducted, along with electrocardiograms and laboratory tests. Safety follow-up will continue up to 42 months after the last dose. The study includes monitoring for serious adverse events and overall survival, with participants remaining under medical supervision throughout the trial duration.

Researchers are conducting the GENESIS clinical study to map the HLA genomic region in the Greek population and explore its possible links with various underlying diseases. This non-interventional, multicenter study aims to provide a pilot map of genetic variation in HLA that may be useful in medical research and clinical applications related to selected diseases. The study plans to include 12,000 participants over a total duration of 36 months. Each participant will attend one visit at a participating site during which they will provide demographic data, lifestyle information such as smoking and alcohol use, blood pressure measurements, details on diagnosed diseases and treatments, and recent laboratory test results if available. Buccal swab samples will be collected from each participant to extract DNA for HLA genotyping analysis. Selected samples will undergo further whole genome sequencing to investigate associations with autoimmune diseases. Participants will receive a personalized ancestry report after analysis completion. During the study visit, data collection includes demographic and health information, as well as laboratory and clinical test results from the past year. The genetic material from buccal swabs will be stored and processed for genetic analysis. Researchers will measure allele frequency of HLA alleles in the Greek population and assess the prevalence and risk associations of selected HLA-related diseases. The study's total duration is 36 months with results available at the end of this period.

Researchers are evaluating the tolerability and pharmacokinetics of TQB3455 tablets in patients with hematological malignancies, specifically acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). TQB3455 is an inhibitor targeting the IDH2 enzyme. The study has two stages: the first focuses on safety and tolerability of single or multiple doses in subjects with malignant blood tumors, while the second investigates the efficacy and safety of TQB3455 alone or combined with azacitidine in AML or MDS patients. During stage one, participants take TQB3455 tablets orally once daily for 28 consecutive days per treatment cycle. In stage two, participants receive the same TQB3455 tablet regimen, and some also receive azacitidine injections subcutaneously on days one through seven of each 4-week cycle. Azacitidine is a drug that affects DNA methylation. The study assesses both single and combination treatments through these cycles. Participants will be monitored with multiple assessments including dose-limiting toxicity and maximum tolerated dose during the first 28 days up to 48 weeks. Researchers will also measure overall remission rates, survival, response duration, and complete remission rates up to 48 weeks, along with detailed pharmacokinetic measurements of TQB3455 over multiple time points. Safety and tolerability are closely followed, and patients will be observed up to 96 weeks for overall survival outcomes.

Researchers are evaluating the safety, tolerability, and effectiveness of TQB3909 tablets combined with azacitidine in adults with myeloid malignancies, including acute myeloid leukemia and myelodysplastic syndromes. This open, multi-center clinical trial is designed as a Phase Ib/II study to better understand how this combination treatment works in these blood cancers. Participants receive TQB3909 tablets once daily in 28-day treatment cycles along with azacitidine. The study focuses on monitoring how well patients tolerate the treatment and its effects on their disease. The trial includes assessment of various response rates and survival outcomes over several weeks. Throughout the trial, participants undergo regular evaluations including monitoring for adverse events and laboratory tests for up to 24 weeks. Researchers measure remission rates, duration of remission, and survival outcomes up to 60 weeks. Participants' safety and response to treatment are closely tracked during the study.