Hematologic Malignancy

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 investigating CGT9486 (bezuclastinib) in a Phase 2 open-label study for adults with Advanced Systemic Mastocytosis (AdvSM), including Aggressive Systemic Mastocytosis (ASM), Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN), and Mast Cell Leukemia (MCL). This study aims to evaluate the drug's safety, efficacy, pharmacokinetics, and pharmacodynamics in these conditions. Participants receive bezuclastinib tablets taken orally in continuous 28-day cycles. The study has two parts conducted over 18 months each: Part I focuses on identifying active and tolerable doses, while Part II assesses treatment effectiveness by measuring the modified IWG Objective Response Rate (ORR) and confirms exposure-response relationships. During the study, participants will undergo evaluations including blood and bone marrow tests, imaging for spleen and liver size, and monitoring of mutation levels and serum tryptase. Researchers will track adverse events, duration and time to response, progression-free and overall survival. The total study duration includes these assessments over 18 months.

This research aims to understand how patients with cancer respond to COVID-19 vaccination by studying the levels of protective antibodies over time. The focus is on individuals with solid organ malignancies receiving various anti-cancer treatments such as chemotherapy, targeted therapy, and immunotherapy, as well as those who have been disease-free for at least six months. Since cancer patients were excluded from initial vaccine trials, this study seeks to fill knowledge gaps about vaccine safety and effectiveness in this group. Participants include cancer patients who are either undergoing active treatment or are disease-free for six months or more. They are grouped based on their treatment type: chemotherapy, targeted therapy, immunotherapy, or disease-free status. The study involves monitoring antibody trends related to COVID-19 infection and vaccination at multiple time points over a 12-month period. During the study, researchers will collect blood samples to measure neutralizing and spike antibody levels every three months for up to one year. Participants will be followed to track their immune response depending on their cancer treatment and biological aging status. The study will also assess how antibody levels change over time and correlate with different treatments and patient characteristics. Safety and consent are carefully monitored throughout the trial.

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.

Researchers are evaluating the potential usefulness of 18F-FAPI-04 positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MR) for diagnosing primary and metastatic cancer lesions, detecting recurrence, and assessing pathological response across various cancer types. The study is observational and aims to assess how well these imaging methods perform compared to standard diagnosis using histopathology and follow-up. Participants with different types of cancer undergo imaging with 18F-FAPI-04 PET/CT and PET/MR scans. The tracer 18F-FAPI-04 is injected into patients before the scans. Tumor uptake is measured by maximum standard uptake value (SUVmax) and tumor to background ratio (TBR). The imaging results are compared using sensitivity, specificity, positive predictive value, negative predictive value, and accuracy to evaluate diagnostic performance. During the study, participants are assessed through these imaging procedures to monitor tumor presence, recurrence, or response to treatment. The primary outcome is the diagnostic performance evaluated over one year. The study includes participants aged 18 to 90 years and involves informed consent and ethical approval. The total duration and follow-up details are based on imaging and clinical evaluations to confirm findings.

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 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.