Bone Marrow Disorder

Researchers are studying the effects of elenestinib (BLU-263) combined with symptom directed therapy (SDT) compared to placebo plus SDT in adults with indolent systemic mastocytosis (ISM) who have symptoms not well controlled by current treatments. This randomized, double-blind, placebo-controlled Phase 2/3 trial includes participants with ISM and smoldering systemic mastocytosis (SSM), aiming to evaluate both safety and efficacy of the treatments. The study is sponsored by Blueprint Medicines Corporation and includes participants who have previously used selective KIT inhibitors as well as pharmacokinetic groups. Participants will be assigned to receive either elenestinib or placebo along with symptom directed therapies tailored individually. Elenestinib is taken orally once daily. The study is organized into multiple parts: Parts 1 and 2 involve treatment periods lasting up to approximately 48 weeks, after which participants in Part 2 may continue into Part 3 and receive open-label elenestinib for up to five years. Part K enrolls those previously treated with KIT inhibitors. Symptom directed therapy doses are stabilized before treatment and maintained throughout. During the trial, participants will be monitored regularly for side effects and symptom changes using the ISM-Symptom Assessment Form (ISM-SAF) and other measures such as serum tryptase levels, KIT D816V allele fraction, bone marrow mast cell counts, and quality of life assessments. Safety will be tracked through adverse event reporting. The study duration can extend up to five years, allowing long-term evaluation of treatment effects and symptom control. Participants will have ongoing evaluations at set intervals including baseline, weeks 13, 24, 48, and beyond as applicable.

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 PET/CT and 18F-FAPI PET/MRI, 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 PET/CT and 18F-FAPI PET/MRI 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 PET/MRI 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 cancer of plasma cells that currently has no cure and often returns after treatment. Survival after diagnosis is typically 5 to 8 years. Researchers are evaluating whether the radiotracer 18F-fluciclovine, injected during PET/CT scans, is better at detecting MM than the commonly used 18F-FDG tracer, aiming to improve early detection and treatment decisions. This is a phase 2, open-label study involving adults with newly diagnosed or relapsed/refractory MM. Participants will receive an intravenous injection of 18F-fluciclovine (370 MBq) and undergo PET/CT scans at three key times: before treatment or early in treatment (newly diagnosed MM), six months after initial scans (relapsed/refractory MM), and either at disease progression or after 5 years. Each visit includes both 18F-fluciclovine and 18F-FDG PET/CT scans, an optional MRI, and a bone marrow biopsy from the hip. The study compares the effectiveness of these imaging methods in detecting MM. During the study, participants will have three visits for imaging and biopsies, with tests spread over about 30 days per visit. Blood tests, disease volume measurements, and bone marrow analysis will be performed to assess disease status and treatment response. Safety of 18F-fluciclovine will be monitored up to three days after each dose. Follow-up includes a final visit after 5 years or upon disease progression, allowing long-term monitoring of MM status.

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 evaluating a new formulation of 64Cu-LLP2A, a drug used with PET/CT imaging, to study its dosimetry and imaging quality in healthy volunteers and patients with certain blood cancers. These cancers include multiple myeloma and various low-grade lymphomas. This early phase 1 study aims to confirm that the new formulation provides similar human dosimetry to previously published results and to expand evaluation to patients with confirmed diagnoses or those post bone marrow transplant with suspected recurrence. Participants will receive 64Cu-LLP2A followed by PET/CT imaging at up to three separate times depending on the injection day of the week. Imaging sessions involve multiple quick body scans within the first hour, additional scans between 120 to 240 minutes, and a later scan 15 to 28 hours post injection. Patients with known lesions will have dynamic imaging centered over those areas for one hour, plus an additional scan from head to upper thigh after injection. During the study, participants will undergo PET/CT scans and monitoring of organ dosimetry and safety for up to seven days after 64Cu-LLP2A administration. Researchers will assess the quality of PET images by looking at bone marrow uptake and tumor-to-background ratios. Safety will be tracked by recording any adverse events. The total imaging and evaluation period is estimated to last up to two days, with additional follow-up phone assessments.

Researchers are evaluating the diagnostic effectiveness of 68Ga FAPI PET/CT 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 PET/CT 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 PET/CT 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 PET/CT 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.