Myelodysplastic Syndrome (MDS)

Researchers are evaluating the use of 18F-Pentixafor PET imaging to improve the diagnosis, staging, and treatment response assessment of various blood cancers, including multiple myeloma, leukemia, and lymphoma. This imaging method targets the chemokine receptor 4 (CXCR-4), which is often found in high amounts in these cancers and is linked with tumor growth and poor outcomes. The study aims to assess how well this new imaging technique performs compared to current standards, especially for a wider range of hematological tumors. In this study, patients receive an intravenous injection of 18F-Pentixafor at a dose of 55 MBq/kg. After waiting 60 minutes post-injection, they undergo PET/CT or PET/MR scans. This new tracer has advantages such as a longer half-life, better image quality, and higher spatial resolution compared to previous similar tracers. Patients can have the PET imaging without special preparation one hour after the injection. Participants include adults aged 18 to 80 years with suspected or confirmed blood cancers. They will undergo baseline imaging and, if needed, biopsies for diagnosis. Researchers will monitor the diagnostic effectiveness of 18F-Pentixafor PET over about 1.5 years. Throughout the study, assessments include imaging, pathological results, and treatment response evaluations. Safety and compliance with study requirements will also be closely observed.

Researchers are evaluating the side effects and optimal dose of a radioactive drug called 211^astatine-BC8-B10 before donor stem cell transplant in adults with high-risk blood cancers including acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or mixed-phenotype acute leukemia. This phase I/II trial studies how this radioactive antibody treatment targets cancer cells while sparing healthy cells prior to transplant. The study focuses on patients needing donor stem cell transplantation to treat their high-risk leukemia or related disorders. Participants receive the 211^astatine-BC8-B10 treatment intravenously over 6-8 hours about one week before their transplant. Some patients may also receive an additional radioactive antibody, 131^I-BC8-B10, and fludarabine phosphate chemotherapy before undergoing total-body irradiation and peripheral blood stem cell transplant on day 0. After transplant, patients take cyclosporine and mycophenolate mofetil medications for several months to prevent complications. Procedures during the study may include SPECT imaging and collection of blood and bone marrow samples. Participants are monitored for side effects up to 100 days after transplant and then checked at 6, 9, 12, 18, and 24 months. Researchers will measure the incidence of serious toxicities related to the Bearman regimen within 100 days post-transplant. The study involves regular assessments of blood tests, imaging, and clinical evaluations to track safety and treatment effects over two years.

Researchers are evaluating a treatment for adults aged 18 to 75 with high-risk acute leukemia or myelodysplastic syndrome that has returned or is not responding to treatment. This phase I/II trial studies the side effects and the best dose of a radioactive antibody called 211At-BC8-B10. This antibody may help prevent cancer cells from growing and spreading. The study also looks at the effects of donor stem cell transplant and medicines to prevent graft versus host disease, where donor cells attack normal cells in the body. Participants receive an infusion of the radioactive antibody 211At-BC8-B10 over 6 to 8 hours on day -8. This is followed by chemotherapy drugs fludarabine and cyclophosphamide on days -6 to -2 and -6 and -5, respectively. Total body irradiation is given on day -1. On day 0, patients undergo stem cell transplant from a donor, either from peripheral blood or bone marrow. After transplant, patients receive medicines including cyclophosphamide, mycophenolate mofetil, and tacrolimus to reduce the risk of graft versus host disease. Granulocyte colony-stimulating factor is started on day 5 to help recover white blood cell counts. During the study, patients have bone marrow biopsies, blood sample collections, and other tests. They are followed closely with visits up to two years after treatment to monitor side effects, especially serious toxicities within 100 days after transplant. The main outcome measured is the proportion of patients who develop severe side effects from the treatment. This research helps understand the safety and appropriate dosing of the radioactive antibody combined with stem cell transplant for these blood cancers.

Researchers are evaluating a new conditioning treatment combining 225Ac-DOTA-Anti-CD38 daratumumab, fludarabine, melphalan, and total marrow and lymphoid irradiation (TMLI) for donor stem cell transplant in patients with high-risk acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS). This phase I trial focuses on testing the safety, side effects, best dose, and potential effectiveness of this combination. Daratumumab is a monoclonal antibody targeting CD38 on certain immune and cancer cells, and when linked to a radioactive substance, it may help kill cancer cells. The study also aims to determine the maximum tolerated dose and recommended phase II dose of this approach. During the treatment, patients receive intravenous daratumumab followed by indium In 111-DOTA-daratumumab and then actinium Ac 225-DOTA-daratumumab approximately 15 days before transplant. Total marrow and lymphoid irradiation is given twice daily over four days, followed by fludarabine over three days and melphalan on the day before the stem cell transplant. Additionally, patients receive graft-versus-host disease (GVHD) prevention with sirolimus and tacrolimus starting one day before transplant. Several scans and biopsies are performed throughout the study, including CT scans, nuclear and SPECT imaging, echocardiography or MUGA scans, and bone marrow sampling. Participants are closely monitored after treatment with visits twice weekly for the first 100 days post-transplant, then twice monthly for six months, and monthly thereafter until immunosuppressive therapy is stopped without GVHD, with at least yearly follow-up for two years. Researchers track adverse events, survival outcomes, relapse rates, and pharmacokinetics of the radioimmunotherapy. Blood samples and imaging help assess treatment safety and effectiveness over time.

Researchers are evaluating the use of 3'-deoxy-3'-[18F] fluorothymidine (FLT) PET imaging to study tumor growth and DNA synthesis activity in patients with various cancers, including brain tumors, leukemia, lymphoma, and solid tumors. This phase I trial aims to see how well FLT PET imaging can detect cancer lesions, measure tumor proliferation, and estimate patients' responses to treatment. Participants receive up to four FLT PET imaging sessions. During each session, a small amount of the tracer compound [F-18] FLT is injected into the veins in a saline solution. PET scan data collection begins immediately and continues for two hours to measure tumor growth. Blood samples may be taken during each scan, and urine samples are collected afterward to analyze how the tracer breaks down. Throughout the study, participants undergo multiple imaging procedures to monitor tumor activity. Researchers measure tracer uptake and retention in tumors and normal tissues and assess changes in related enzymes and uptake values before and after therapy. Participants must be able to lie still during scans and meet certain physical and reproductive health criteria. The study includes safety precautions such as pregnancy testing and contraception requirements for fertile patients.

Researchers are exploring a new treatment approach for myelodysplastic syndromes (MDS) and related myeloid malignancies, conditions where the bone marrow fails to produce enough healthy blood cells. This trial studies a combination therapy using low doses of two drugs, 5-azacitidine and decitabine, given alternately to overcome resistance mechanisms seen when these drugs are used alone. This is a single-arm, open-label early phase 1 pilot study aiming to evaluate the overall response rate of this alternating regimen in participants with MDS or MDS/myeloproliferative overlap disorders who have shown potential sensitivity to hypomethylating agent therapy. Participants will receive 5-azacitidine at 50 mg/m² on Day 1 each week and decitabine at 5 mg/m² on Day 4 each week, with or without granulocyte-colony stimulating factor (G-CSF). Treatment will continue for at least 24 weeks unless the disease clearly progresses. Those who respond to the treatment may continue until relapse or progression that does not improve with dose escalation as defined by the study protocol. During the study, participants will be closely monitored for their response, including complete and partial responses and hematologic improvements. Safety will be assessed by tracking significant adverse events. Additional laboratory studies will explore correlations between drug effects and biological markers. The primary outcome is the overall response rate up to six months after treatment ends. The study includes ongoing assessments of disease status, side effects, and biological markers over the treatment period and beyond.

Researchers are investigating HMPL-506, an oral drug, in a Phase 1 clinical study for patients with hematological malignancies such as relapsed or refractory acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), and multiple myeloma (MM). The study has two phases: dose escalation and dose expansion, aiming to determine the safest and most effective dose. Approximately 60 to 132 patients are expected to participate, including those with specific genetic mutations or rearrangements related to these blood cancers. In the dose escalation phase, patients receive increasing doses of HMPL-506 orally once daily in 28-day cycles to identify the maximum tolerated dose and recommended Phase 2 dose. Initial doses start at 50 mg daily, with potential escalation based on safety and efficacy data. The dose expansion phase enrolls patients into three cohorts based on disease type and genetics, treating them with the recommended dose in 28-day cycles until disease progression, intolerable side effects, or other defined reasons to stop. Participants will undergo regular safety monitoring, including evaluation of dose-limiting toxicities, serious adverse events, and response to treatment. Tumor response is assessed every cycle for the first six cycles and then every two cycles thereafter, with follow-up lasting up to 42 months. Additional assessments include bone marrow biopsies, laboratory tests, and performance status evaluations. The study tracks participants until disease progression, withdrawal, or study completion to evaluate HMPL-506's safety and preliminary effectiveness.

Researchers are conducting the GENESIS clinical study to map the HLA genomic region in the Greek population and explore possible links to certain diseases. This multicenter, prospective, non-interventional study plans to enroll around 12,000 adults over 36 months. The goal is to create a pilot map of HLA genetic variation to support medical research and potential clinical uses, including evaluating connections with various health conditions such as respiratory, cardiovascular, metabolic, neurological, psychiatric, gastrointestinal, hematologic, rheumatologic diseases, and chronic renal failure. During the study, participants will visit a participating site once to provide demographic information, lifestyle habits, medical history, and recent clinical lab test results if available. Two buccal swabs will be collected from each participant for DNA extraction and HLA genotyping analysis. Selected samples will also undergo full low-pass whole genome sequencing to further study associations between the HLA region and autoimmune diseases. After analysis, participants can securely access a personalized ancestry report if they wish. Participants will be asked about their health, lifestyle, and medical treatments, and provide samples for genetic testing. Researchers will monitor the allele frequency of HLA alleles at the Greek population level over 36 months. The study includes secure data handling and offers long-term follow-up through genetic and ancestry reports. This comprehensive approach aims to enhance understanding of genetic variation and its possible disease correlations in Greece.

Researchers are evaluating the safety, tolerability, and pharmacokinetics of TQB3455 tablets in adults with hematological cancers, specifically acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). TQB3455 is an inhibitor targeting the IDH2 mutant enzyme. The study is divided into two phases: the first phase assesses safety and tolerability of single or multiple doses in patients with malignant blood tumors, while the second phase studies the efficacy and safety of TQB3455 alone or in combination with azacitidine for injection in AML or MDS patients. The treatment involves oral administration of TQB3455 tablets, either alone or combined with azacitidine, a drug used for demethylation therapy. The study aims to determine the maximum tolerated dose and observe dose-limiting toxicities. Participants receive the investigational treatment according to assigned groups, with ongoing safety monitoring during the study period lasting up to 48 weeks. Participants will undergo assessments including monitoring for dose-limiting toxicities, overall remission rates, and pharmacokinetic evaluations throughout the study. Safety and efficacy data will be collected up to 48 weeks, with follow-up visits to assess treatment response and adverse events. The total duration includes baseline screening, treatment phases, and extended monitoring to evaluate the drug's impact and tolerability in hematological malignancy patients.

Researchers are conducting a Phase Ib/II clinical trial to assess the safety, effectiveness, and how the body processes TQB3909 tablets combined with azacitidine in adults with myeloid malignancies, which include diseases like acute myeloid leukemia and myelodysplastic syndromes. The study aims to evaluate how well patients tolerate this combination and its impact on their condition. Participants will receive TQB3909, a protein inhibitor, along with azacitidine, a cytidine nucleoside analogue. The treatment is administered as tablets, and the study is open-label and multi-center. The trial focuses on monitoring adverse events for up to 24 weeks and measuring remission rates within 4 weeks after starting treatment. During the study, participants will undergo various evaluations to track safety and treatment response, including monitoring for side effects and laboratory tests. Researchers will record the incidence and severity of any adverse events and assess the rate of complete remission or remission with partial blood recovery. Participants must be adults aged 18 years or older and will be followed closely for up to 24 weeks to ensure safety and effectiveness of the treatment combination.