Myelodysplastic Syndrome

This MyeloMATCH Master Screening and Reassessment Protocol (MSRP) evaluates the use of a screening tool and specific laboratory tests to help improve participants' ability to register to clinical trials throughout the course of their myeloid cancer (acute myeloid leukemia or myelodysplastic syndrome) treatment. This study involves testing patients' bone marrow and blood for certain biomarkers. A biomarker (sometimes called a marker) is any molecule in the body that can be measured. Doctors look at markers to learn what is happening in the body. Knowing about certain markers can give doctors more information about what is driving the cancer and how to treat it. Testing patients' bone marrow and blood will show doctors if patients have markers that specific drugs can target. The marker testing in this study will let doctors know if they can match patients with a treatment study (myeloMATCH clinical trial) that tests treatment for the type of cancer they have or continue standard of care treatment with their doctor on the Tier Advancement Pathway (TAP).

In transfusion-dependent myelodysplastic syndromes patients, regular blood transfusions lead to iron overload, which can cause organ damage, hormonal imbalances, and increased infection risk, ultimately impacting patient survival. Standard oral iron chelation therapies can be intolerable for some patients due to adverse effects. The MEX-CD1 device (class III) could potentially offer an alternative for these patients by reducing serum iron levels through a novel, extracorporeal approach. MEXIRON clinical investigation focuses on the use of MEX-CD1, a medical device designed for extracorporeal chelation therapy to reduce iron overload in patients suffering from transfusion-dependent myelodysplastic syndromes (MDS) and myelofibrosis. MEXIRON aims to evaluate the device's use feasibility, safety, and effectiveness in reducing iron levels. Transfusions needs, patient experience and quality of life are also assessed. Each enrolled patients will undergo three low-volume continuous veno-venous haemodialysis cycles within one week. Following the three- haemodialysis cycles, patients will be monitored through on-site follow-up visits at 7 days, 28 days, and 90 days post-treatment to assess long-term effects.

The goal of this clinical trial is to learn if agenT-797 is safe to use on people undergoing allogenic hematological stem cell transplantation (SCT). The main questions it aims to answer are: * Is agenT-797 safe to use? * What medical problems do participants have when taking agenT-797? Participants will receive an infusion of agenT-797 about 7 days after their allogenic SCT.

A non-randomized phase Ib study of PC14586 (PMV therapeutics) in patients diagnosed with TP53Y220C-mutant myeloid malignancies, including AML and MDS.

This phase II trial tests the effect of total marrow and lymphoid irradiation (TMLI) in combination with fludarabine and melphalan as conditioning regimen in older patients with acute myeloid leukemia or high-risk myelodysplastic syndrome that has not responded to previous treatment (refractory) and that has come back after a period of improvement (relapsed) and are undergoing a donor (allogeneic) peripheral blood stem cell (PBSC) hematopoietic cell transplant (HCT) from a matched related or unrelated donor. HCT is the only curative treatment for high-risk patients, but the side effects related to the current conditioning treatments limit the use to younger and more fit patients. TMLI is a targeted form of total body radiation that uses intensity-modulated radiation therapy to target marrow, lymph node chains, and the spleen. It is designed to reduce radiation-associated side effects and maximize the radiation therapeutic effect. Fludarabine blocks cells from making deoxyribonucleic acid (DNA) and may kill cancer cells. It is a type of purine antagonist and a type of ribonucleotide reductase inhibitor. Melphalan is in a class of medications called alkylating agents. It may kill cancer cells by damaging their DNA and stopping them from dividing. Giving chemotherapy, such as fludarabine and melphalan, and TMLI before an allogeneic transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells to grow. When healthy stem cells from a related or unrelated donor, such as PBSC HCT, that closely match the patient's blood, are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets, an may help destroy any remaining cancer cells. Giving TMLI in combination with fludarabine and melphalan as conditioning treatment for an allogeneic PBSC HCT from a matched related or unrelated donor may be safe, tolerable, and/or effective in treating high-risk older patients with relapsed and refractory acute myeloid leukemia or high-risk myelodysplastic syndrome.

This phase II MyeloMATCH treatment trial compares the usual treatment of cedazuridine-decitabine (ASTX727) to the combination treatment of ASTX727 and enasidenib in treating patients with higher-risk, IDH2-mutated myelodysplastic syndrome (MDS). ASTX727 is a combination of two drugs, decitabine and cedazuridine. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Enasidenib is an enzyme inhibitor that may stop the growth of cells by blocking some of the enzymes needed for cell growth. Giving ASTX727 in combination with enasidenib may be effective in treating patients with higher-risk IDH2-mutated MDS.

This phase I trial tests the safety, side effects, and best dose of SM08502 (cirtuvivint) alone and in combination with ASTX727 in treating patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Cirtuvivint may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. ASTX727 is a combination of two drugs, decitabine and cedazuridine. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Giving cirtuvivint alone or in combination with ASTX727 may be safe, tolerable, and/or effective in treating patients with AML and MDS.

This phase II trial studies whether providing cancer treatment in the home is preferred over the traditional clinic setting and if it improves treatment satisfaction in cancer patients living in the Florida Panhandle and surrounding areas. Typically, drug-related cancer care is provided at a medical center which causes patients to have to spend considerable time away from their family, friends, and familiar surroundings. This may add to the physical, emotional, social, and financial burden for patients and their families during this difficult time in their lives. The Cancer Connected Access and Remote Expertise (CARE) Beyond Walls (CCBW) program uses a specialized care team trained to provide cancer treatment in the patient's home setting. It is designed to support remote connection between the home health team and providers and Mayo clinic. This may be preferred over the traditional clinic setting which may improve treatment satisfaction in cancer patients living in the Florida Panhandle and surrounding areas.

Evaluation of the safety, tolerability, pharmacokinetics, and preliminary efficacy of XS-04 in patients with relapsed or refractory hematologic malignancies

This phase I/II trial studies how well quizartinib, decitabine, and venetoclax work in treating participants with acute myeloid leukemia or high risk myelodysplastic syndrome that is untreated or has come back (relapsed). Quizartinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as decitabine and venetoclax, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving quizartinib and decitabine may work better at treating acute myeloid leukemia and myelodysplastic syndrome.

This phase II MyeloMATCH treatment trial tests luspatercep with or without epoetin alfa or emavusertib for the treatment of low risk myelodysplasia and anemia. Biological therapies, such as luspatercep, use substances made from living organisms that may attack specific cancer cells and stop them from growing or kill them. Epoetin alfa is a substance that is made in the laboratory and stimulates the bone marrow to make red blood cells. Emavusertib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving luspatercep with or without epoetin alfa or emavusertib may be effective for treating patients with low risk myelodysplasia and anemia.

This study is not designed to test a hypothesis; rather, this study will provide patients with access to Orca-T if the commercial Orca-T product produced for them is deemed out of specification (OOS). Serious adverse events (SAEs) occurring during the safety reporting period (defined as the day the recipient receives the Orca-T HSPC drug product through day +365 after transplantation or until initiation of new anticancer therapy, whichever occurs sooner) will be reported.

The main aim of this study is to assess how elritercept works in lowering the need for RBC (red blood cell) transfusions and how safe elritercept is when compared with epoetin alfa. Other aims are to learn if elritercept improves tiredness as reported by participants without needing RBC transfusion compared with epoetin alfa, the RBC transfusion burden and quality of life compared with epoetin alfa. The study also aims to find out the extent of the immune response to elritercept. The study will also check on the medical problems (safety) of elritercept.

This phase I trial studies the side effects and best dose of edetate calcium disodium or succimer in treating patients with acute myeloid leukemia or myelodysplastic syndrome undergoing chemotherapy. Edetate calcium disodium or succimer may help to lower the level of metals found in the bone marrow and blood and may help to control the disease and/or improve response to chemotherapy.

Clonal hematopoiesis (CH), including clonal hematopoiesis of indeterminate potential (CHIP), is an age-associated condition characterized by the expansion of hematopoietic stem and progenitor cell clones carrying acquired somatic mutations. Although CH is associated with an increased risk of hematologic malignancies, its greater public health impact derives from its strong association with cardiovascular diseases, including coronary artery disease and stroke. Emerging evidence suggests that CH-associated mutations promote chronic inflammatory signaling in myeloid immune cells, thereby contributing to atherosclerosis and adverse cardiovascular remodeling. This observational translational study aims to characterize the biological spectrum of clonal hematopoiesis across different stages of disease risk and manifestation. Using state-of-the-art single-cell and multi-omics approaches, the study will compare inflammatory pathways, immune cell states, and mutation-associated molecular programs among healthy individuals without CH, individuals with high-risk CH, and patients with CH-associated hematologic or cardiovascular disease. The ultimate goal is to identify shared and disease-specific mechanisms linking clonal hematopoiesis to adverse clinical outcomes and to generate insights for future preventive, anti-clonal, and anti-inflammatory therapeutic strategies.

This phase II trial studies how well decitabine with ruxolitinib, fedratinib, or pacritinib works before hematopoietic stem cell transplant in treating patients with accelerated/blast phase myeloproliferative neoplasms (tumors). Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ruxolitinib, fedratinib, and pacritinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving chemotherapy before a donor hematopoietic stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer 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. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells. Decitabine, with ruxolitinib, fedratinib, or pacritinib may work better than multi-agent chemotherapy or no pre-transplant therapy, in treating patients with accelerated/blast phase myeloproliferative neoplasms.

Background: -Patients who are being evaluated and/or treated at the NIH Clinical Center and adult patients at participating sites will be entered onto this tissue procurement protocol for collection of tissue specimens. Objectives: * To obtain samples from adult and pediatric patients for research purposes from tests and procedures that are done as required by the primary research protocol(s) to which a patient is enrolled or as part of their standard-of-care treatment. * To obtain samples for research purposes from non-surgical procedures, such as percutaneous biopsies, performed for the sole purpose of obtaining tissue specimens or biological fluids for this protocol. Eligibility: -Adult patients (18 years of age and older) and pediatric patients (younger than 18 years of age) who are being evaluated for and/or treated for cancer at the NIH Clinical Center participating sites. Design: * This is a multicenter tissue procurement protocol with NCI as the coordinating center. * For adult patients: specimens for research purposes, as outlined in this protocol, will be obtained from tests and procedures that are done as required by the primary research protocols to which a patient is enrolled or as part of their standard-of-care treatment. Non-surgical procedures, such as percutaneous biopsies, may also be performed for the sole purpose of obtaining tissue specimens or biological fluids for this protocol. Tissues and biological fluids to be procured may include but are not limited to blood, serum, urine, tumor tissue, normal tissue, pleural fluid, CSF, saliva, bronchial alveolar lavage (BAL), circulating tumor cells, hair follicles, and bone marrow. These specimens will be stored with unique identifiers and used to perform only those research studies that are outlined in this protocol. * For pediatric patients: tumor biopsy/resection tissue used for pediatric preclinical model development will only be from tissue already being obtained as part of a procedure necessary for the patient s clinical care or as part of a primary research protocol; blood specimens will be collected as part of a blood collection already scheduled for the patient s clinical care or as part of the planned pre-procedure bloodwork; volumes collected will not exceed institutional research limits. * Given the risks associated with any invasive procedure, such as tumor biopsy, the procedure will be discussed in detail with the patients and their parents/guardian (as indicated), including the side effects, prior to obtaining a separate consent for each procedure. A separate consent will not be signed prior to obtaining samples by minimally invasive measures, such as venipuncture. * This study has two separate consent forms at the NIH Clinical Center: one for adult patients to donate specimens for ongoing research on assay development and studies of molecular pathways, and one for adult and age-appropriate pediatric patients to donate samples for the generation of preclinical models. The study also has consent form templates for adult and pediatric patients at participating sites to donate specimens to create preclinical models. * Patients may remain on study for the duration of their consent or completion of the planned procedure, whichever comes first.

This phase II trial studies how well enasidenib and azacitidine work in treating patients with IDH2 gene mutation and acute myeloid leukemia that has come back (recurrent) or does not respond to treatment (refractory). Enasidenib and azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

This phase Ib/II trial studies the side effects and best dose of venetoclax and how well it works when given together with ivosidenib with or without azacitidine, in treating patients with IDH1-mutated hematologic malignancies. Venetoclax and ivosidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ivosidenib and venetoclax with azacitidine may work better in treating patients with hematologic malignancies compared to ivosidenib and venetoclax alone.

This phase II trial tests how well removing CD45RA positive naive T cells works to prevent graft versus host disease in older patients undergoing standard of care allogeneic hematopoietic stem cell transplantation for the treatment of acute leukemia or myelodysplastic syndrome (MDS). Allogeneic hematopoietic stem cell transplantation is when healthy cells are collected from a donor and infused into a patient to help the patient's bone marrow make more healthy cells and platelets and help destroy any remaining cancer cells. Giving chemotherapy and total-body irradiation before a stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. Sometimes the transplanted cells from a donor can attack the body's normal cells (called graft-versus-host disease). Removing the T cells from the donor cells before the transplant may stop this from happening. Giving CD45RA positive naive T cell depleted allogenic hematopoietic stem cell transplant may prevent graft versus host disease while treating acute leukemia or myelodysplastic syndrome in older adults.

This phase II MyeloMATCH treatment substudy tests the addition of olutasidenib to usual treatment in patients with higher-risk myelodysplastic syndrome (MDS) or patients with acute myeloid leukemia (AML) with a mutation in the IDH1 gene. Olutasidenib blocks the protein made by the mutated IDH1 gene. Blocking this protein may help keep cancer cells from growing. For patients with MDS, olutasidenib will be added to decitabine-cedazuridine (also called ASTX727). Decitabine is in a class of medications called hypomethylating agents and is the standard treatment for MDS. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. The cedazuridine makes it possible to take the decitabine by mouth. Adding olutasidenib to the usual treatment for MDS (ASTX727) may increase the likelihood of going into remission. For patients with AML, olutasidenib and ASTX727 will be combined with venetoclax, a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. Venetoclax may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Adding olutasidenib to the usual treatment for AML (ASTX727 and venetoclax) may increase the likelihood of going into remission. For low risk MDS, the substudy tests whether giving olutasidenib alone helps improve blood counts.

This phase I/II trial studies the best dose of gilteritinib given together with ASTX727 and venetoclax and the effect of ASTX727, venetoclax, and gilteritinib in treating patients with FLT3-mutated acute myeloid leukemia that is newly diagnosed, has come back (relapsed) or does not respond to treatment (refractory) or high-risk myelodysplastic syndrome. Chemotherapy drugs, such as ASTX727, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Gilteritinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving ASTX727, venetoclax, and gilteritinib may help to control the disease.

Cytokine profiles in the early post-transplant phase may influence the Development of early post-transplant inflammatory or immunological complications. This study propose to analyze these cytokine profiles based on the disease (myelofibrosis or other hematologic malignancies) and on the donor type (haploidentical, genotypically identical, or phenotypically identical). Patients with myelofibrosis have an inflammatory cytokine profile prior to transplantation. Patients who undergo haploidentical allogeneic hematopoietic stem cell transplantation (HSCT) most often experience a post-transplant cytokine release syndrome, and the question is whether these two conditions-myelofibrosis and haploidentical transplantation-increase the probability of an early cytokine release, potentially putting these patients at greater risk for acute GVHD than patients who undergo transplantation under other conditions or who have other diseases. In the prospective Phase 2 "FIBRAPLO" protocol (ClinicalTrials.gov ID NCT04728490), 28 patients with myelofibrosis received an allogeneic hematopoietic stem cell transplantation from a haploidentical donor, and serum samples were collected at Day-7 before transplantation, Day 0 and Day+7 after transplantation to analyse cytokine profiles around the time of allogeneic HSCT. The purpose of the present study is to match these FIBRAPLO patients (patients with myelofibrosis who received an allograft from a haploidentical donor) with patients without myelofibrosis who received a haploidentical transplant, in order to determine whether these profiles are specific to this population. The aim is to compare these profiles to other scenarios: patients with or without myelofibrosis who received transplants from 10/10 or geno-identical donors. This study propose to prospectively collect blood samples at time points (D-7, D0, and D7) from control patients : * receiving a haplo-identical allogeneic transplant for another condition (acute leukemia, myelodysplastic syndrome), * a geno-identical or 10/10 matched unrelated allogeneic transplant, for myelofibrosis or for other condition (acute leukemia, myelodysplastic syndrome)

This is a Phase 1, open label, dose-escalation study to evaluate the safety, expansion, persistence, and preliminary clinical activity of lentivirally transduced autologous T cells expressing anti-CD64 chimeric antigen receptors (CAR) expressing tandem CD3ζ and 4-1BB (CD3ζ/4-1BB) costimulatory domains in subjects with refractory or relapsed (R/R) acute myeloid leukemia (AML). This CAR T cell product will be referred to as "CD64 CAR T" which is CD64 directed, autologous, genetically modified CAR T cells. The primary objective of the study is to identify the safety profile and maximum tolerated dose (MTD) of CD64 CAR T in subjects with R/R AML as determined by the defined DLTs using a standard Bayesian Optimal Interval (BOIN) design.

This phase II trial investigates how well CPX-351 and ivosidenib work in treating patients with acute myeloid leukemia or high-risk myelodysplastic syndrome that has IDH1 mutation. The safety of this drug combination will also be studied. IDH1 is a type of genetic mutation (change). Chemotherapy drugs, such as CPX-351, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ivosidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. The purpose of this trial is to learn if CPX-351 in combination with ivosidenib can help to control IDH1-mutated acute myeloid leukemia or high-risk myelodysplastic syndrome.