Myelodysplastic Syndromes

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.

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.

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.

To learn if olutasidenib can help to control CCUS, MDS, and/or CMML. The safety of the drug will also be studied.

The purpose of this study is to test the feasibility and safety of early cessation of tacrolimus following allogeneic hematopoietic cell transplantation (HCT). Post-HCT tacrolimus is given to prevent graft-vs-host-disease (GVHD), but with the use of post-transplant cyclophosphamide (PTCy), the modern approach to GVHD prevention, GVHD rates have reduced markedly.

The goal of this study is to test an electronic health (eHealth) mindfulness-based music therapy intervention to improve health-related quality of life and reduce symptom burden and disease activity in patients undergoing stem cell transplantation.

Patients diagnosed with hematologic cancer are at substantial risk of dying, as 5-year survival among patients with acute myeloid leukemia is 20 % and only every second patient treated for incurable myeloma lives 5 years after date of diagnosis. Nevertheless, many overestimate their prognosis, and value of therapy. Patients with hematological cancers frequently have poor end of life outcomes, such as high treatment activity close to death, where clinical effects are doubtful, and low utilization of palliative care. Prognostic awareness and end of life (EOL) issues have urgency in the communication between patients, their caregiving relatives, and clinicians, in order to avoid futile treatments and suffering at EOL. Inspired by advanced care planning, the investigators developed the concept "Advance Consultations Concerning participants Life and Treatment" (ACT) in collaboration with a group consisting of hematologists, nurses, patients, and caregivers. The ACT concept consists of an 8-hour training day for clinicians, clinical tools, system changes, and preparation material for patients and caregivers prior to the consultation. ACT involves patients and caregivers earlier in preparation for life with chronic progressive disease and EOL-decisions, through an intervention based on compassionate communication and early planning of EOL-care. The aim of the study is to investigate the effect of the intervention on use of chemotherapy and quality of EOL-care in patients with hematological malignancy. Based on the results of the completed pilot study, the investigators are planning a nationwide 2-arm cluster randomized controlled trial where 40 physicians and 80 nurses across seven different hematological departments are randomized to either usual care or ACT training and completing ACT conversations. The investigators expect to include a total of 400 patients and their family caregivers. It is hypothesized that the ACT intervention will decrease use of futile chemotherapy, prepare patients and caregivers for difficult end-of-life-decisions, and improve quality of end-of-life care in hematology.

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.

This phase 2 study aims to confirm the efficacy observed in the prior phase 1 trial in Cohort 1 and to evaluate the safety of IFN-γ in combination with DLI in Cohort 2, the haploidentical donor alloSCT recipient cohort. The study will further contribute to this effort through the collection of leukemia cells pre- and post-in vivo IFN-γ therapy. As in the previously conducted phase 1 trial, this trial will assess whether leukemia blasts are responsive to IFN-γ in vitro and in vivo. Single-cell RNA sequencing (scRNAseq) will be performed to evaluate transcriptomic changes induced by IFN-γ in leukemia cell subsets, including those with stem cell characteristics.

The goal of this project is to test non-invasive, painless skin electrical bioimpedance (BioZ) measurements as an adjunctive biomarker to standard bone marrow biopsies.

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 (5 years from the first dose of the study drug or 3 years after the last dose, whichever is longer). 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.

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.

The primary objective of this study is to evaluate the efficacy and safety of ofirnoflast administered orally once daily in adults with very low- to intermediate-risk myelodysplastic syndromes (MDS) who are transfusion-dependent and have failed one to three prior therapies, in order to identify the optimal dose for continuation into a Phase 3 study. The secondary objectives of this study are to evaluate the extended hematologic response to ofirnoflast, to assess the safety and tolerability of ofirnoflast during the dose-selection phase, and to evaluate hematologic improvement with ofirnoflast treatment.

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.

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.

Patients with clonal cytopenia of undetermined significance (CCUS) and lower-risk myelodysplastic syndromes (MDS) have a life expectancy of 5 to 10 years. Mortality in these patients results from progression of disease to higher-risk MDS or acute myeloid leukemia (AML) and cardiovascular events. Currently there are no FDA-approved treatments with the potential to improve survival of patients with CCUS and lower-risk MDS. Statins are an appealing class of drugs to consider in this situation as preclinical data support their potential to suppress progression of myeloid malignancy, and they have a well-established role in prevention of major cardiovascular events. This is a pilot study to explore the role of statins in treatment of patients with CCUS and lower-risk MDS. In this study, change in inflammatory biomarkers and variant allele frequency (VAF) of somatic mutations will be used as a surrogate marker of response to statin therapy. The hypothesis is that the use of statins at diagnosis of CCUS or lower-risk MDS will reduce inflammation and delay or prevent the expected increase in the VAF of somatic mutations over time.

The study is designed to determine the efficacy and safety of roxadustat for the treatment of anemia due to very low, low, or intermediate risk MDS in participants with high transfusion burden (HTB).

This research study is a genomic profiling and repository study for children and young adults who have leukemia, myelodysplastic syndrome (MDS) or myeloproliferative syndrome (MPS). Genes are the part of cells that contain the instructions which tell cells how to make the right proteins to grow and work. Genes are composed of DNA letters that spell out these instructions. Genomic profiling helps investigators understand why the disease develops and the instructions that led to its development. Understanding the genetic factors of the disease can also help investigator understand why the disease of some people can respond to certain therapies differently than others. The genomic profiling will be performed using bone marrow and blood samples that either have already been obtained during a previous clinical procedure or will be obtained at the time of a scheduled clinical procedure. Studying the genetic information in the cells of these samples will provide information about the origin, progression, and treatment of leukemia and myeloproliferative syndromes and myelodysplastic syndrome. Storing the bone marrow and blood samples will allow for additional research and genomic assessments to be performed in the future.

This is a Phase I dose finding study of GTB-3650 (anti-CD16/IL-15/anti-CD33) Tri-Specific Killer Engager (TriKE®) for the treatment of select CD33-expressing refractory/relapsed myeloid malignancies in adults ≥ 18 years of age who are not a candidate for potentially curative therapy, including hematopoietic stem cell transplantation, and are refractory to, intolerant of, or ineligible for therapy options that are known to provide clinical benefit. The hypothesis is GTB-3650 TriKE will induce natural killer (NK) cell function by targeting malignant cells, as well as, CD33+ myeloid derived suppressor cells (MDSC) which contribute to a tumor induced immunosuppression. Because CD16 is the most potent activating receptor on NK cells, this single agent may induce a targeted antiCD33+ tumor response

This study tests whether a combination of three treatments - dexamethasone (a steroid), intravenous immunoglobulin (IVIG, a protein that helps the immune system), and an extra dose of donor mononuclear cells - can safely lower harmful antibodies called donor-specific antibodies (DSA) in patients who need a stem cell transplant from a half-matched (haploidentical) family donor. In these transplants, DSA are antibodies made by the patient's own body that attack the donor's stem cells. If DSA levels are high, the transplant is more likely to fail - the donor cells may not "take" (engraft). Currently, there is no single, simple, and reliable way to reduce DSA, and many existing methods have drawbacks. Based on the investigators' earlier experience in 11 patients, this three-part approach seemed to work well. All patients successfully engrafted, and DSA levels dropped quickly. Now the study team want to confirm these results in a larger, prospective, multicenter study. The investigators plan to enroll 60 patients aged 18-65 with blood cancers or other blood disorders who need a haploidentical transplant, have DSA levels above 500 MFI (a measure of antibody strength), and have no other suitable donor available. Participants will receive: * Dexamethasone (25 mg/m²) for 4 days before transplant, * IVIG (1 g/kg) one day before transplant, * Extra mononuclear cells on transplant day - the extra amount depends on how high their DSA level is (low, medium, or high). The main goal is to see how many patients have primary graft failure (when the donor cells never engraft). The study team will also measure how long it takes for blood counts to recover, rates of graft-versus-host disease, survival, and side effects. All participants will be followed for 1 year. This study will help the investigators find out whether this combination is a safe, simple, and effective way to improve transplant success for patients with DSA who have no other donor options.

The study will determine the safety, tolerability, recommended Phase 2 dose (RP2D) and preliminary efficacy of BGB-11417 as monotherapy and in combination with azacitidine in participants with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)or MDS/myeloproliferative neoplasm (MPN) .

The major morbidities of allogeneic hematopoietic stem cell transplant with non-human leukocyte antigen (HLA) matched siblings are graft vs host disease (GVHD) and life threatening infections. T depletion of the donor hematopoietic stem cell graft is effective in preventing GVHD, but immune reconstitution is slow, increasing the risk of infections. An addback of donor CD45RA (naive T cells) depleted cells may improve immune reconstitution and help decrease the risk of infections.

This study will evaluate the safety, tolerability, and efficacy of Orca-T in participants undergoing reduced intensity or non-myeloablative allogeneic hematopoietic cell transplantation (alloHCT) for hematologic malignancies. Orca-T is an allogeneic stem cell and T-cell immunotherapy biologic manufactured for each patient (transplant recipient) from the mobilized peripheral blood of a specific, unique donor. It is composed of purified hematopoietic stem and progenitor cells (HSPCs), purified regulatory T cells (Tregs), and conventional T cells (Tcons).

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.

This is a Phase II study following subjects proceeding with our Institutional non-myeloablative cyclophosphamide/ fludarabine/total body irradiation (TBI) preparative regimen followed by a related, unrelated, or partially matched family donor stem cell infusion using post-transplant cyclophosphamide (PTCy), sirolimus and MMF GVHD prophylaxis.