Myelodysplastic Syndromes Clinical Trials

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. Read Less

Reduced intensity conditioning (RIC) has emerged and been increasingly adopted as a modality to allow preparative conditioning pre transplant to be tolerated by older adults or those patients that are otherwise unfit for myeloablative conditioning. In this study, we aim to use RIC followed by matched related/unrelated donor, 7/8 matched related/unrelated donor, or haploidentical donor peripheral blood stem cell transplantation. Standard strategies to control the alloreactivity following HCT utilize immunosuppressive or cytotoxic medications. In this study, we explore donor graft engineering to enrich for immmunoregulatory populations to facilitate post transplantation immune reconstitution while minimizing graft versus host disease (GVHD) with post-transplant immunosuppressive agents. Read Less

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. Read Less

This is a multi-center, non-randomized, concurrent controlled, multi-arm, Phase 1 interventional, open-label, biologic assignment-based umbrella study evaluating the feasibility, safety and preliminary efficacy of an escalating dose regimen of up to 2 doses of TSC-100 and TSC-101 in patients with AML, MDS, or ALL following HCT from a haploidentical donor. Read Less

This is a two Part study in patients with relapsed/refractory acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), or high risk myelodysplastic syndrome (MDS) that will initially evaluate the safety and tolerability of APG-115 as a single agent in Part 1, followed by a combination of APG-115 + 5-azacitidine (5-AZA) in Part 2. Read Less

RATIONALE: Giving chemotherapy, such as busulfan, fludarabine, and melphalan, before a donor umbilical cord blood stem cell transplant helps stop the growth of abnormal or cancer cells and prepares the patient's bone marrow for the 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 may stop this from happening. PURPOSE: This phase II trial is studying how well combination chemotherapy followed by a donor umbilical cord blood transplant works in treating infants with high-risk acute leukemia or myelodysplastic syndromes. Read Less

The purpose of the study is to see if participants with anemia due to their type of MDS or MDS/MPN will experience a more decreased need for regular blood transfusions if they take luspatercept plus best supportive care, and what effect, good and/or bad, luspatercept has on them and their anemia due to MDS or MDS/MPN. The safety and tolerability of luspatercept will also be evaluated in this study. Read Less

This is a study to assess the safety of increasing dose levels of bexmarilimab when combined with standard of care (SoC) in patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) or acute myeloid leukemia (AML); Phase 1 aims to identify the recommended phase 2 dose (RP2D) of bexmarilimab based on safety, tolerability and pharmacological activity; Phase 2 will investigate the preliminary efficacy of the combination treatment in selected indications from Phase 1. Read Less

Patients with medical conditions requiring allogeneic hematopoietic cell transplantation (allo-HCT) are at risk of developing a condition called graft versus host disease (GvHD) which carries a high morbidity and mortality. This is a phase I/II study that will test the safety and efficacy of hematopoietic cell transplantation (HCT) with ex-vivo T cell receptor Alpha/Beta+ and CD19 depletion to treat patients' underlying condition. This process is expected to substantially decrease the risk of GvHD thus allowing for the elimination of immunosuppressive therapy post-transplant. The study will use blood stem/progenitor cells collected from the peripheral blood of parent or other half-matched (haploidentical) family member donor. The procedure will be performed using CliniMACS® TCRα/β-Biotin System which is considered investigational. Read Less

CP-MGD024-01 is a Phase 1, open-label, multi-center study of MGD024 as a single agent in patients with select blood cancers that have not responded to treatment with standard therapies or who have relapsed after treatment. The study is designed to determine the safety, tolerability, pharmacokinetics (affect of the body on the drug), pharmacodynamic (affect of the drug on the body), immunogenicity (development of antibodies against the drug), and preliminary anti-cancer effect of MGD024. Patients will receive treatment with MGD024 in consecutive 28-day cycles for a study treatment period of up to 12 cycles (approximately 1 year) or until treatment or study discontinuation criteria are met. Response assessments will be performed after Cycle 1 and then after every even numbered cycle starting with Cycle 2 until progression or study treatment discontinuation. Patients will be checked for side effects throughout the study. Read Less

This phase II clinical trial evaluates whether a modified modality of conditioning reduces treatment-related mortality (TRM) in patients who undergo a hematopoietic stem cell transplant (HSCT) for a hematological malignancy. HSCT is a curative therapy for many hematopoietic malignancies, however this regimen results in higher rates of TRM than other forms of treatment. In recent years, less intense conditioning regimens with radiation and chemotherapy prior to HSCT have been developed. Radiation therapy uses high energy sources to kill cancer cells and shrink tumors while chemotherapy drugs like fludarabine and cyclophosphamide 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. This study evaluates whether a two-step approach with lower-intensity regimens of these treatments prior to HSCT reduces the rate of TRM. Read Less

This research study is evaluating the safety and efficacy of the IS-free Treg-cell graft-engineered haplo transplant method in people with relapsed/refractory and Ultra-high risk acute myeloid leukemia (AML) and/or myelodysplastic syndromes (MDS) receiving a haploidentical donor allogeneic hematopoietic stem cell transplant (HSCT). The names of the study interventions involved in this study are: Radiation-Total Myeloid and Lymphoid Irradiation (TMLI Chemotherapy (Fludarabine, Thiotepa, Cyclophosphamide plus Mesna) Infusion of haplo Treg-enriched donor cells (experimental therapy) Infusion of unmodified haplo donor T cells (includes cancer-fighting T effector cells) Infusion of haplo donor CD34+ Peripheral Blood Stem Cells Read Less