Clinical Research Directory

Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms

Background: Myelodysplastic syndrome (MDS) and myelodysplastic/myeloproliferative neoplasm (MDS/MPN) are blood disorders that can cause serious complications in children and adults. MDS and MDS/MPN can also progress to acute myeloid leukemia. Treatments for these disorders are risky and not always effective. Better treatments are needed. Objective: To test a study drug (pacritinib) in adults and children with MDS or MDS/MPN. Eligibility: Children (aged 12 to 17 years) and adults (aged 18 years and older) with MDS or MDS/MPN. Design: Participants will be screened. They will have a physical exam with blood tests. They will have tests of their heart function. They may have a bone marrow biopsy: An area over the hip will be numbed; a needle will be inserted to remove a sample of soft tissue from inside the hipbone. Pacritinib is a capsule taken by mouth. All participants will take the study drug 2 times a day, every day, in 28-day cycles. They will write down the date and time they take each capsule. Doctors will assign varying dosages of the drug to different participants. Participants will have clinic visits each week during cycle 1; every 2 weeks during cycle 2; and gradually increasing to every 3 months after cycle 13. Treatment will continue for up to 8 years. Bone marrow biopsies, heart tests, and other tests will be repeated at intervals throughout the study. Participants will also fill out questionnaires about their quality of life, the symptoms of their disease, and other topics.

Mosaic Trial for Stem Cell Transplant Recipients

The goal of this clinical trial is to learn if using an intervention website (Mosaic) improves selected patient-reported outcomes in adult blood cancer patients undergoing allogeneic or autologous stem cell transplant, compared to using an educational website (control group). Patients will be recruited prior to their scheduled transplant, then randomized to use one of these two study websites throughout the study. They will complete five assessments during the study: one before transplant (baseline) and four after transplant (2, 4, 6, and 8 month follow-ups). The main questions this trial aims to answer are: 1. Compared to patients using the control group website, do patients using the intervention website report greater improvements in general psychological distress, cancer treatment-related distress, physical symptoms, and health-related quality of life? 2. Are these benefits at least partially explained by improvements in perceived preparedness, self-efficacy, and approach coping and/or reductions in avoidant coping and perceived stress? 3. Do some patients benefit more from using the intervention website than others? Specifically, we will examine whether patients' primary language (English/Spanish) and their initial psychological distress are related to the benefit they get from using the intervention website. We will also explore effects of sex, race, ethnicity, and transplant type.

Study of REM-422 in Patients With AML or Higher Risk MDS

The goal of this study is to determine the safety and antitumor effects of REM-422, a MYB mRNA degrader, in people with Higher Risk MDS and relapsed/refractory AML

A Study of TAK-226 for Anemia in Japanese Patients With Lower-Risk Myelodysplastic Syndromes

The main aim of the study is to evaluate how TAK-226 improves symptoms of transfusion-dependent anemia in Japanese patients with lower-risk myelodysplastic syndromes. The study consists of Screening Period (up to 6 weeks), Treatment Period, Safety Follow-Up Period (8 weeks), and Long-Term Follow-Up Period (approximately 5 years from the first dose of the study treatment). Participants of this study will be administered TAK-226 during Treatment Period. Subsequently, the participants will be monitored for side effects related to the study treatment during Safety Follow-Up Period and Long-Term Follow-Up Period. The approximate duration of participation for a participant is up to approximately 6 years. During the study period, participants will visit the study clinic/hospital multiple times as per the study schedule. During Treatment Period, the participants will come to the clinic/hospital approximately every two to four weeks.

HEME Home Transfusion Program

This research study is evaluating whether a new care delivery program that provides access to home blood transfusions in hospice (i.e, HEME-Hospice) compared to regular standard of care improves quality of life, mood, and end-of-life health care utilization for patients with hematologic malignancies.

Tissue, Blood, and Body Fluid Sample Collection From Patients With Hematologic Cancer

RATIONALE: Collecting and storing samples of tissue, blood, and body fluid from patients with cancer to study in the laboratory may help the study of cancer in the future. PURPOSE: This research study is collecting and storing blood and tissue samples from patients being evaluated for hematologic cancer.

Efficacy and Safety of Maximum Labeled Dose Luspatercept in Lower-Risk Myelodysplastic Syndromes

This study is a single-arm, prospective, multi-center, Phase IIIb clinical trial aimed at evaluating the efficacy and safety of the maximum labeled dose of luspatercept in individuals diagnosed with lower-risk myelodysplastic syndromes (MDS). The trial anticipates the enrollment of 75 participants with lower-risk MDS, all of whom will undergo treatment with luspatercept.

A Study of Elritercept to Treat Anemia in Adults With Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS) Who Need Regular Blood Transfusions

The main aim of this study is to find out how well elritercept works in lowering the need for RBC transfusions. Other aims are to learn how well elritercept works in reducing the need for RBC transfusions over longer periods of time or in adults with high transfusion needs. The study will also check on how safe elritercept is and how well it is tolerated.

Anakinra for Prevention of Poor Graft Function in MDS Allo-HSCT

Preclinical evidence indicates that IL-1 inflammatory signaling suppresses bone marrow mesenchymal stromal cells (MSCs) from secreting stem cell factor (SCF), leading to failure of their hematopoietic supportive capacity, and that the interleukin-1 receptor antagonist (IL-1Ra, Anakinra) can reverse this process. Sustained low-level IL-1 signaling also drives hematopoietic stem cell (HSC) dysfunction, including progression of clonal hematopoiesis and transformation to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). A prior phase 2 trial of IL-1 inhibition in lower-risk MDS demonstrated hematologic improvement without an increased risk of leukemic transformation. Based on these findings, this study hypothesizes that early administration of Anakinra after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with MDS, by inhibiting IL-1β signaling, improving the bone marrow microenvironment, and reducing the occurrence of poor graft function (PGF), does not increase the risk of post-transplant relapse. The study comprises two parts: a dose-escalation phase to determine the maximum tolerated dose (MTD) / recommended phase 2 dose (RP2D) of Anakinra in post-allo-HSCT patients, and an efficacy-validation phase to evaluate the preventive effect of Anakinra at the RP2D on PGF.

Study of DISC-0974 (RALLY-MF) in Participants With Myelofibrosis or Myelodysplastic Syndrome and Anemia

This phase 1b/2a open-label study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of DISC-0974 as well as categorize the effects on hematologic response in participants with myelofibrosis or myelodysplastic syndrome and anemia.

Whole Genome Sequencing (ChromoSeq) as an Adjunct to Conventional Genomic Profiling in AML and MDS

This is a single institution, prospective study of the whole genome sequencing assay, ChromoSeq. Using prospectively collected patient data, coupled with physician surveys, the investigators seek to determine the feasibility of implementing ChromoSeq in addition to standard genomic testing, for patients with the diagnoses of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

Study of Efficacy and Safety of Eltrombopag in Lower-risk MDS Patients With Platelet Transfusion Dependence

This study is designed to evaluate the efficacy and safety of eltrombopag monotherapy in Japanese adult patients with platelet transfusion-dependent lower-risk Myelodysplastic syndromes (LR-MDS).

MBG453 in Lower Risk MDS

This research study is assessing the efficacy of MBG-453, a humanized monoclonal antibody, in treating myelodysplastic syndromes (MDS). The name of the study drug involved in this study is MBG453.

Clofarabine and High-Dose Melphalan Followed by Donor Stem Cell Transplant in Patients With Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Myelodysplastic Syndromes

RATIONALE: Giving chemotherapy, such as clofarabine and melphalan, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. PURPOSE: This phase I trial is studying the side effects and best dose of clofarabine when given together with high-dose melphalan followed by a donor stem cell transplant in treating patients with acute myeloid leukemia, acute lymphocytic leukemia, or myelodysplastic syndromes.

A Study of Elritercept to Treat Anemia in Adults With Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS)

The main aim of this study is to learn how safe elritercept is and how well adults with anemia associated with lower-risk MDS tolerate treatment with different doses of elritercept. Other aims are to learn how safe elritercept is by looking at how many participants have MDS that worsens during the study and learn about the effects of elritercept on anemia linked to MDS. The study will also look to learn how elritercept affects the production of healthy RBCs.

Leukemia and Lymphoma Society (LLS) Services Impact on Outcomes and Care

The purpose of this study is to learn about the impact that the services and programs provided by Blood Cancer United (formerly, The Leukemia and Lymphoma Society) have among patients with blood cancer, such as access to care, quality of life, and financial burden.

Collection of Blood, Bone Marrow, Skin, Saliva, and Stool Samples From Healthy Volunteers Used for Comparative Analysis of Myeloid Malignancies

Background: Myelodysplastic syndromes (MDS) are disorders of blood stem cells that can develop into blood cancers. Treatment options are limited. To find better treatments, researchers need to better understand how MDS develops. To do that, they must be able to compare biospecimens from people with the disease to those of healthy people. Objective: This study will create a database of biospecimens collected from healthy volunteers. Eligibility: Healthy people aged 18 and older. Design: Participants will be screened. They will have a physical exam with blood and urine tests. Up to 5 types of samples will be collected on 1 or more days within 1 month of screening: Blood: Blood will be drawn by inserting a needle into a vein. Saliva: Participants will scrape the insides of their cheeks with a brush. Stool: Participants will be given a container to collect stool at home. They will use a prepaid envelope to mail in the sample. Bone marrow: A sample of the soft tissue inside the bones will be drawn out. The area to be biopsied, usually the lower back, will be numbed. A needle will be inserted through a small cut to remove the sample. Participants' pain will be monitored; additional numbing medicine may be used. Skin: A piece of skin about 1/6 of an inch across will be cut away. Stitches may be used to close the wound. Participants will return to the clinic to have the stitches removed. Participants do not have to provide all of the samples listed. They will give each sample only once.

Study of Individuals and Families With Aberrations in DDX41 or Similar Cancer Predisposition Variants

Background: Hereditary hematopoietic malignancy (HHM) syndromes are a group of inherited disorders that raises the risk of blood cancers. Many people with HHMs have changes in a gene (DDX41) that makes it more likely that they will develop myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), or other cancers. This natural history study will explore the link between HHM syndromes and these diseases. Objective: To study the link between HHM and MDS/AML. Eligibility: People aged 1 month and older with HHM. Relatives with HHM are also needed. Design: Participants aged 3 years and older will have 1 initial clinic visit with the option to follow-up annually. They will undergo these procedures: They will have a physical exam with blood and urine tests. They may give samples of saliva, stool, nails, and skin. Their ability to do normal activities will be reviewed. Some may have a bone marrow biopsy: A tissue sample will be drawn from inside a bone. They may answer questions about their health and family medical history. Participants younger than 3 years, and those who cannot come to the clinic, will be contacted by phone or email. Their samples may be collected locally and sent to researchers. For participants who have changes in their DDX41 gene: Researchers will contact them or their primary care provider once a year for 10 years. Researchers will check on participants health and collect any new test results. Some may be asked to send new samples. Participants who do not have changes in their DDX41 gene may be contacted yearly, or less often, for 10 years. Some participants may be asked to return to the clinic if needed.

Comprehensive Molecular and Clinical Evaluation of Pediatric and Adult MDS

Background: Myelodysplastic syndromes (MDS) occur when the cells that make blood cells are abnormal. There are limited treatment options for MDS. Researchers want to learn more through this natural history study so they can develop better treatments. Objective: To study the natural course of MDS and MDS/myeloproliferative neoplasms (MPN) and collect biological samples that can help researchers understand the disease. Eligibility: People with suspected or confirmed MDS or MDS/MPN. Healthy donors are also needed. They can be people who are scheduled to donate bone marrow at NIH for a relative, or they may be providing bone marrow in another study. Design: Participants will be screened with a medical history. Participants will have a physical exam. They will give blood and urine samples. They will discuss their symptoms, medications, and ability to perform their normal activities. They will complete surveys about how they are feeling. Participants will have a bone marrow biopsy. A needle will be inserted through a small cut. Bone marrow will be removed. A small piece of bone may be removed. Participants may have an optional skin biopsy. Participants may give optional saliva and stool samples. They may collect these samples at home and mail them to NIH. Participants may undergo optional apheresis. One or two needles or intravenous (IV) lines will be placed in their arm, neck, or groin veins. Blood will be removed. A machine will separate out the white cells. The rest of the blood will be returned to the participant. Participants will be contacted for follow-up once a year for up to 20 years. Healthy donors will have marrow collected for this study during their scheduled procedure with no follow-up.

PK/Efficacy Bridging Study of ASTX727 in Chinese Subjects With Myelodysplastic Syndromes

This is an Open-Label, Crossover, Pharmacokinetic and Efficacy Bridging Study of Oral ASTX727 versus IV Decitabine in Chinese Subjects with Myelodysplastic Syndromes

Molecular and Clinical Analysis of Bone Marrow Failure: A Secondary Research Study

STUDY DESCRIPTION: Bone marrow failure can result from immune mediated attack on stem cells or from inherited genetic defects such as telomere biology disorders or Fanconi anemia. Aplastic anemia (AA), a prototype of bone marrow failure syndromes (BMFS), can be acquired or inherited. Acquired BMFS have common immune mediated pathophysiology, and include AA, lower risk myelodysplastic syndrome (MDS, particularly hypoMDS), VEXAS, large granular lymphocytosis (LGL), paroxysmal nocturnal hemoglobinuria (PNH), pure red cell aplasia (PRCA), or cytopenia of undetermined origin. Clonality is frequent in patients with BMFS. Patients with acquired AA are known to have somatic mutations in phosphatidylinositol glycan class A (PIGA), BCL6 corepressor (BCOR) and HLA genes, which are all related to the immune mediated pathophysiology and good predictors of treatment and overall outcomes. Others such as ASXL1, RUNX1, and splicing factor mutations and/or chromosome 7 aneuploidy are associated with secondary myeloid neoplasms in these patients. Somatic mutations in STAT, DNMT3A and TET2 are prevalent in many other BMFS, such as LGL and VEXAS. Except for acquired AA, the clonal dynamics and trajectories, and cooccurrence of these aberrations in other BMFS are poorly understood. How these clonal events interact with epigenetic and proteomic changes are also unknown. In addition, the role of novel genetic defects in marrow failure is poorly characterized, such as mutations associated with inborn errors of immunity or complement pathways. Our aim is to elucidate this further using multi-omics, bulk/single cell DNA and RNA techniques as well as understand the epigenetics using ATAC-seq, and proteomics. The translation work will be correlated with clinical outcomes and laboratory parameters of patients with the particular BMFS cohort being investigated. OBJECTIVES: Primary Objective: To characterize the molecular aberrations in BMFS and to understand how clonality, epigenetics, and proteomics contribute to hematopoiesis over the course of disease using high resolution multi-omics characterization of hematopoietic stem and progenitor cells (HSPC), immune cells and other cellular composition in peripheral blood and bone marrow samples. Secondary Objectives: * To correlate the molecular findings with disease presentation and clinical outcomes (response to treatment, clonal evolution to secondary myeloid neoplasm, survival) * To correlate molecular findings with clinical laboratory data, cytokine, chemokine, soluble receptor levels and growth factors * To correlate findings with peripheral or marrow flow cytometry phenotyping * To correlate findings on this study with already performed germline or somatic mutational data * To compare the genomic, epigenomic and proteomic findings with healthy age matched controls

Danvatirsen Monotherapy Followed by Combination With Venetoclax in Relapsed/Refractory MDS & AML

This is a Phase 1 study investigating the safety and efficacy of Danvatirsen as a monotherapy followed by combination with Venetoclax in patients with relapsed/refractory myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). Funding Source: FDA OOPD

Phase I Study of FXS0683 in the Treatment of Blood Tumors

This is a first-in-human, multicenter, open-label, single-arm Phase I study of FXS0683 in participants with relapsed or refractory hematologic malignancies to evaluate safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity, and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D).

HLA-mismatched Microtransplantation Without Immunosuppressive Treatment in Patients With Myeloid Hemopathies

This study aims at evaluating the safety of an approach based on HLA-mismatched Microtransplantation without immunosuppressive treatment in patients With myeloid hemopathies who are ineligible to conventional allograft