Bone Marrow Disorder

Researchers are evaluating the safety and effectiveness of elenestinib BLU-263 combined with symptom directed therapy SDT compared to placebo plus SDT in adults with indolent systemic mastocytosis ISM whose symptoms are not well controlled by SDT alone. This randomized, double-blind, placebo-controlled Phase 23 study includes multiple parts to assess different doses and durations of elenestinib treatment, including an open-label extension for participants finishing earlier phases. The study also enrolls participants who have previously received an approved selective KIT inhibitor and includes pharmacokinetic groups. Participants receive oral elenestinib or placebo once daily alongside SDT, which is personalized based on individual symptom management needs. Part 1 focuses on short-term treatment lasting up to 12 weeks, while Part 2 extends treatment to approximately 48 weeks. Part 3 and other parts allow treatment for up to about 5 years. The study monitors participants through these phases to evaluate how elenestinib affects symptoms, disease markers, and safety over time. During the study, participants undergo regular assessments of symptoms using the ISM-Symptom Assessment Form ISM-SAF, laboratory tests including serum tryptase and KIT D816V allele levels, bone marrow evaluations, and quality of life measures. Researchers track adverse events and changes in disease-related factors at various points up to 5 years. This thorough monitoring helps measure treatment effects and safety over both short and long-term periods, with total participation lasting several years depending on the study part.

Researchers are studying myelofibrosis MF, a disease involving abnormal bone marrow fibrosis, stem cell growth, and inflammation, which is difficult to monitor due to invasive biopsy methods. This observational study aims to assess the usefulness and accuracy of two imaging techniques, 18F-FDG PETCT and 18F-FAPI PETMRI, in evaluating systemic fibrosis in MF patients. The study will also explore how these imaging results relate to patients clinical outcomes. Participants diagnosed with primary or secondary myelofibrosis will undergo both 18F-FDG PETCT and 18F-FAPI PETMRI scans. The study design is prospective, observational, self-controlled, and conducted across multiple centers. Imaging, hematologic, cytogenetic, and pathological assessments will be performed within two weeks of each other. Patients must be stable and able to cooperate with the imaging procedures. During the study, participants will be monitored over an average of two years to evaluate the diagnostic performance of 18F-FAPI PETMRI and compare clinical prognoses based on imaging and pathology results. The study will include assessments such as imaging scans and clinical follow-up. Safety and adherence to protocol will be tracked, with informed consent required. The goal is to improve noninvasive monitoring of myelofibrosis progression and treatment effects.

Multiple myeloma MM is a type of blood cancer that currently has no cure and often returns after treatment, leading to a survival time of about 5 to 8 years after diagnosis. Researchers are studying whether a new imaging substance called 18F-fluciclovine can detect MM more effectively than the currently used 18F-FDG. This trial is a phase 2 study focused on adults with MM, including those newly diagnosed or with relapsedrefractory disease, aiming to improve early detection of returning disease. Participants will receive an injection of the radiotracer 18F-fluciclovine and undergo PETCT scans at three different times initially, after treatment for newly diagnosed participants or six months for relapsedrefractory participants, and at disease progression or after 5 years. Each visit includes two PETCT scansone with 18F-FDG and one with 18F-fluciclovineas well as an optional MRI scan and a bone marrow biopsy. The study compares the imaging results from both tracers to assess which better detects MM lesions. During the study, participants will attend three visits where tests and scans will be performed, possibly spread over 30 days per visit. Blood tests, imaging scans, and bone marrow samples will help researchers measure disease volume, minimal residual disease, and response to treatment. Safety of the new radiotracer is also monitored shortly after each dose. Participation may last up to 5 years, with follow-up visits scheduled to track disease progression and imaging results.

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.

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 mgm on Day 1 and DEC at 5 mgm 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 evaluating a new formulation of 64Cu-LLP2A, a drug used for PETCT imaging, in both healthy volunteers and patients with blood cancers such as multiple myeloma and low-grade lymphoma. This early phase study aims to confirm that the new formulation provides comparable human dosimetry to the previous formulation while expanding the patient population to include those with confirmed diagnoses or those who have undergone bone marrow transplant with suspected disease recurrence. Participants will receive the 64Cu-LLP2A drug followed by PETCT imaging at up to three different time points depending on the day of injection. Imaging includes multiple quick body scans shortly after injection, scans at 120-180 or 180-240 minutes post-injection, and a delayed scan 15-28 hours later. Some participants will also undergo a dynamic PETCT scan focused on a known target lesion for 60 minutes, followed by an additional whole-body scan. During the study, participants will be monitored for organ dosimetry and safety through adverse event tracking up to 7 days after administration. The quality of PET images will be assessed based on overall image quality, bone marrow uptake, and tumor-to-background ratios. Participants must lie still within the scanner for up to 75 minutes during imaging sessions. The study is expected to complete by March 2027.

Researchers are evaluating the use of BCMA-targeted positron emission tomographycomputed tomography PETCT scans in patients with multiple myeloma and related plasma cell disorders. This prospective, multicenter diagnostic imaging study aims to visualize and measure BCMA expression throughout the body, helping to detect active disease and its variations. The study focuses on how this imaging method may provide valuable clinical information across different disease states. Participants will receive the 68Ga-labeled BCMA PETCT imaging through an intravenous injection of a BCMA-targeted radiotracer followed by a whole-body scan following a standardized protocol. Imaging results will be compared with biopsy findings when possible to assess accuracy. The study will also explore relationships between PETCT findings and other clinical, laboratory, and imaging markers, including minimal residual disease assessments. Some participants will have blood samples taken to measure circulating soluble BCMA levels, providing additional biological context. During the study, participants will undergo the PETCT imaging and may have biopsies and blood tests as part of assessments. Researchers will analyze imaging findings alongside clinical and laboratory data to understand disease burden and response. Safety of the radiotracer will be monitored for up to 30 days after injection. Follow-up will assess changes in imaging over time and the impact on clinical management. The study is expected to last until December 2027 and includes adults aged 18 to 80 years.

Researchers are evaluating the diagnostic effectiveness of 68Ga FAPI PETCT imaging for patients with myelofibrosis, a condition affecting the bone marrow. The study aims to compare this imaging technique with conventional CT scans and to identify different fibrosis grades using bone marrow biopsy as the reference standard. This observational study seeks to determine how well 68Ga FAPI PETCT detects myelofibrosis by measuring sensitivity, specificity, and prediction rates. Participants include those with suspected or confirmed myelofibrosis and patients with primary or secondary myelofibrosis who have not been treated with ruxolitinib. The main intervention is the 68Ga FAPI PETCT scan, which involves lying on a scanning bed for about 20 minutes. The study does not involve treatment but focuses on diagnostic imaging to assess the disease. During the study, participants will undergo the 68Ga FAPI PETCT scan and bone marrow biopsy. Researchers will evaluate diagnostic accuracy by tracking sensitivity, specificity, positive prediction rate, and negative prediction rate over up to 24 months. Participants will be monitored for their ability to complete the imaging and adherence to study protocols, with safety considerations including excluding those with allergies or intolerance to the imaging agent and those with certain health conditions.