67 Clinical Trials for Various Conditions
Background: Bone marrow failure diseases are rare. Much is known about the diseases at the time of diagnosis, but long-term data about the effects of the diseases and treatments are lacking. Researchers want to better understand long-term outcomes in people with these diseases. Objective: To follow people diagnosed with acquired or inherited bone marrow failure disease and study the long-term effects of the disease and its treatments on organ function. Eligibility: People aged 2 years and older who have been diagnosed with acquired or inherited bone marrow failure or Telomere Biology Disorder. First degree family members may also be able to take part in the study. Design: Participants will be screened with a medical history, physical exam, and blood tests. They may have a bone marrow biopsy and aspiration. For this, a large needle will be inserted in the hip through a small cut. Marrow will be drawn from the bone. A small piece of bone may be removed. Participants may also be screened with some of the following: Cheek swab or hair follicle sample Skin biopsy Urine or saliva sample Evaluation by disease specialists (e.g., lung, liver, heart) Imaging scan of the chest Liver ultrasounds Six-Minute Walk Test Lung function test Participants will be put into groups based on their disease. They will have visits every 1 to 3 years. At visits, they may repeat some screening tests. They may fill out yearly surveys about their medicines, transfusions, pregnancy, bleeding, and so on. They may have other specialized procedures, such as imaging scans and ultrasounds. Participation will last for up to 20 years.
This is a Phase II prospective trial to assess the rates of donor engraftment using reduced intensity conditioning (RIC) hematopoietic stem cell transplant (HSCT) and post-transplant cyclophosphamide (PTCy) for patients with primary immune deficiencies (PID), immune dysregulatory syndromes (IDS), and inherited bone marrow failure syndromes (IBMFS).
The goal of this clinical research study is to determine whether it is safe and practical to give CK0801 (a Cord blood-derived T-regulatory cell product) to patients with bone marrow failure syndrome. Researchers want to determine the highest possible dose that is safe to be given. Researchers also want to learn if CK0801 may improve the symptoms of bone marrow failure syndrome. Patients enrolled in this study will all have been diagnosed with treatment refractory bone marrow failure syndrome (which includes aplastic anemia, myelodysplastic syndrome, or myelofibrosis). Participants eligible to participate in this study are unable or unwilling to be treated with standard therapy or have failed standard therapy.
This is a pilot study to determine whether fludarabine-based reduced intensity conditioning (RIC) regimens facilitate successful donor engraftment of patients with acquired aplastic anemia (AA) and Inherited bone marrow failure (iBMF) syndromes undergoing Matched related donor bone marrow transplant (MRD-BMT).
Background: * Stem cell transplants from related donors (allogenic stem cell transplants) can be used to treat individuals with certain kinds of severe blood diseases or cancers, such as severe anemia. Allogenic stem cell transplants encourage the growth of new bone marrow to replace that of the recipient. Because stem cell transplants can have serious complications, researchers are interested in developing new approaches to stem cell transplants that will reduce the likelihood of these complications. * By reducing the number of white blood cells included in the blood taken during the stem cell collection process, and replacing them with a smaller amount of white blood cells collected prior to stem cell donation, the stem cell transplant may be less likely to cause severe complications for the recipient. Researchers are investigating whether altering the stem cell transplant donation procedure in this manner will improve the likelihood of a successful stem cell transplant with fewer complications. Objectives: - To evaluate a new method of stem cell transplantation that may reduce the possibly of severe side effects or transplant rejection in the recipient. Eligibility: * Recipient: Individuals between 4 and 80 years of age who have been diagnosed with a blood disease that can be treated with allogenic stem cell transplants. * Donor: Individuals between 4 and 80 years of age who are related to the recipient and are eligible to donate blood. OR unrelated donors found through the National Marrow Donor Program. Design: * All participants will be screened with a physical examination and medical history. * DONORS: * Donors will undergo an initial apheresis procedure to donate white blood cells. * After the initial donation, donors will receive injections of filgrastim to release bone marrow cells into the blood. * After 5 days of filgrastim injections, donors will have apheresis again to donate stem cells that are present in the blood. * RECIPIENTS: * Recipients will provide an initial donation of white blood cells to be used for research purposes only. * From 7 days before the stem cell transplant, participants will be admitted to the inpatient unit of the National Institutes of Health Clinical Center and will receive regular doses of cyclophosphamide, fludarabine, and anti-thymocyte globulin to suppress their immune system and prepare for the transplant. * After the initial chemotherapy, participants will receive the donated white blood cells and stem cells as a single infusion. * After the stem cell and white blood cell transplant, participants will have regular doses of cyclosporine and methotrexate to prevent rejection of the donor cells. Participants will have three doses of methotrexate within the week after the transplant, but will continue to take cyclosporine for up to 4 months after the transplant. * Participants will remain in inpatient care for up to 1 month after the transplant, and will be followed with regular visits for up to 3 years with periodic visits thereafter to evaluate the success of the transplant and any side effects.
Bone marrow failure syndromes (BMFS) are rare disorders characterized by dysfunctional hematopoietic stem cells, which give rise to all red and white blood cells. The deficiency of blood cells, or cytopenia, caused by this malfunction leads to an assortment of diseases and disorders, all of which are characterized as BMFS. Because these diseases are rare, conducting research on them is difficult, and standards of treatment for most BMFS have yet to be developed. This study will collect clinical and laboratory data from people with BMFS to identify the characteristics and biological markers associated with these diseases over time. This information will assist doctors and researchers to develop better therapies and diagnostic tests that will help improve the management of BMFS and cytopenias.
RATIONALE: Giving chemotherapy and total body irradiation before a donor bone marrow transplant or peripheral blood stem cell transplant helps stop the growth of cancer 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 antithymocyte globulin and removing the T cells from the donor cells before transplant may stop this from happening. PURPOSE: This phase I trial is studying the side effects and best dose of donor T cells and antithymocyte globulin when given together with chemotherapy and total-body irradiation in treating young patients who are undergoing T-cell depleted donor stem cell transplant for myelodysplastic syndrome, leukemia, bone marrow failure syndrome, or severe immunodeficiency disease.
The purposes of this study are: * To examine the engraftment rate in patients receiving in vivo T-cell-depleted G-CSF stimulated bone marrow from partially mismatched related donors. * To evaluate the incidence and severity of acute and chronic graft-versus-host disease in patients receiving in vivo T-cell-depleted G-CSF stimulated bone marrow from partially mismatched related donors.
The researchers hypothesize that it will be possible to perform unrelated bone marrow or cord blood transplants in a safer manner by using less intensive therapy yet still achieve an acceptable level of donor cell engraftment for non-malignant congenital bone marrow failure disorders.
Background: A prospective cohort of Inherited Bone Marrow Failure Syndrome (IBMFS) will provide new information regarding cancer rates and types in these disorders. Pathogenic variant(s) in IBMFS genes are relevant to carcinogenesis in sporadic cancers. Patients with IBMFS who develop cancer differ in their genetic and/or environmental features from patients with IBMFS who do not develop cancer. These cancer-prone families are well suited for cancer screening and prevention trials targeting those at increased genetic risk of cancer. Carriers of IBMFS pathogenic variant(s) are at increased risk of cancer. The prototype disorder is Fanconi's Anemia (FA); other IBMFS will also be studied. Objectives: To determine the types and incidence of specific cancers in patients with an IBMFS. To investigate the relevance of IBMFS pathogenic variant(s) in the carcinogenesis pathway of the sporadic counterparts of IBMFS-associated cancers. To identify risk factors for IBMFS-related cancers in addition to the primary germline pathogenic variant(s). To determine the risk of cancer in IBMFS carriers. Eligibility: North American families with a proband with an IBMFS. IBMFS suspected by phenotype, confirmed by pathogenic variant(s) in an IBMFS gene, or by clinical diagnostic test. Fanconi's anemia: birth defects, marrow failure, early onset malignancy; positive chromosome breakage result. Diamond-Blackfan anemia: pure red cell aplasia; elevated red cell adenosine deaminase. Dyskeratosis congenita: dysplastic nails, lacey pigmentation, leukoplakia; marrow failure. Shwachman-Diamond Syndrome: malabsorption; neutropenia. Amegakaryocytic thrombocytopenia: early onset thrombocytopenia. Thrombocytopenia absent radii: absent radii; early onset thrombocytopenia. Severe Congenital Neutropenia: neutropenia, pyogenic infections, bone marrow maturation arrest. Pearson's Syndrome: malabsorption, neutropenia, marrow failure, metabolic acidosis; ringed sideroblasts. Other bone marrow failure syndromes: e.g. Revesz Syndrome, WT, IVIC, radio-ulnar synostosis, ataxia-pancytopenia. First degree relatives of IBMFS-affected subjects as defined here, i.e. siblings (half or full), biologic parents, and children. Grandparents of IBMFS-affected subjects. Patients in the general population with sporadic tumors of the types seen in the IBMFS (head and neck, gastrointestinal, and anogenital cancer), with none of the usual risk factors (e.g. smoking, drinking, HPV). Design: Natural history study, with questionnaires, clinical evaluations, clinical and research laboratory test, review of medical records, cancer surveillance. Primary endpoints are all cancers, solid tumors, and cancers specific to each type of IBMFS. Secondary endpoints are markers of pre-malignant conditions, such as leukoplakia, serum or tissue evidence of carcinogenic viruses, and bone marrow morphologic myelodyplastic syndrome or cytogenetic clones.
RATIONALE: Although used primarily to treat malignant disorders of the blood, allogeneic stem cell transplantation can also cure a variety of non-cancerous, inherited or acquired disorders of the blood. Unfortunately, the conventional approach to allogeneic stem cell transplantation is a risky procedure. For some non-cancerous conditions, the risks of this procedure outweigh the potential benefits. This protocol is designed to test a new approach to allogeneic stem cell transplantation. It is hoped that this approach will be better suited for patients with non-cancerous blood and bone marrow disorders.
Background: Runt-related transcription factor 1 (RUNX1) gene regulates the formation of blood cells. People with mutations of this gene may bleed or bruise easily; they are also at higher risk of getting cancers of the blood, bone marrow, and lymph nodes. Objective: To test a drug (imatinib) in people with RUNX1 mutations that cause symptoms. Eligibility: Adults aged 18 and older with RUNX1 mutations. Healthy people without this mutation, including family members of affected participants, are also needed. Design: Participants with the RUNX1 mutation will be screened. They will have a physical exam with blood and urine tests. They will have a test of their heart function. They may need a new bone marrow biopsy: A sample of soft tissue will be removed from inside a bone. Imatinib is a tablet taken by mouth once a day, every day, at home. Affected participants in different parts of the study will take imatinib for either 28 days or up to 84 days. Participants will visit the clinic once a week for the first 28 days that they are taking the imatinib. Then they will come once every 2 weeks if they are taking the drug for 84 days. Blood, urine, and tests of heart function will be repeated. They may opt to have the bone marrow biopsy repeated after they finish their course of imatinib. Participants will have a follow-up visit 30 days after they stop taking imatinib. Participants who do not have the RUNX1 mutation will have 1 clinic visit. They will have blood tests. They will fill out questionnaires. They may opt to have a bone marrow biopsy....
This phase II trial tests whether treosulfan, fludarabine, and rabbit antithymocyte globulin (rATG) work when given before a blood or bone marrow transplant (conditioning regimen) to cause fewer complications for patients with bone marrow failure diseases. Chemotherapy drugs, such as treosulfan, 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. Fludarabine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. rATG is used to decrease the body's immune response and may improve bone marrow function and increase blood cell counts. Adding treosulfan to a conditioning regimen with fludarabine and rATG may result in patients having less severe complications after a blood or bone marrow transplant.
In this study, the investigators test 2 dose levels of thiotepa (5 mg/kg and 10 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG) to determine the minimum effective dose required for reliable engraftment for subjects undergoing hematopoietic stem cell transplantation for non-malignant disease.
The purpose of this study is to collect and store samples and health information for current and future research to learn more about the causes and treatment of blood diseases. This is not a therapeutic or diagnostic protocol for clinical purposes. Blood, bone marrow, hair follicles, nail clippings, urine, saliva and buccal swabs, left over tissue, as well as health information will be used to study and learn about blood diseases by using genetic and/or genomic research. In general, genetic research studies specific genes of an individual; genomic research studies the complete genetic makeup of an individual. It is not known why many people have blood diseases, because not all genes causing these diseases have been found. It is also not known why some people with the same disease are sicker than others, but this may be related to their genes. By studying the genomes in individuals with blood diseases and their family members, the investigators hope to learn more about how diseases develop and respond to treatment which may provide new and better ways to diagnose and treat blood diseases. Primary Objective: * Establish a repository of DNA and cryopreserved blood cells with linked clinical information from individuals with non-malignant blood diseases and biologically-related family members, in conjunction with the existing St. Jude biorepository, to conduct genomic and functional studies to facilitate secondary objectives. Secondary Objectives: * Utilize next generation genomic sequencing technologies to Identify novel genetic alternations that associate with disease status in individuals with unexplained non-malignant blood diseases. * Use genomic approaches to identify modifier genes in individuals with defined monogenic non-malignant blood diseases. * Use genomic approaches to identify genetic variants associated with treatment outcomes and toxicities for individuals with non-malignant blood disease. * Use single cell genomics, transcriptomics, proteomics and metabolomics to investigate biomarkers for disease progression, sickle cell disease (SCD) pain events and the long-term cellular and molecular effects of hydroxyurea therapy. * Using longitudinal assessment of clinical and genetic, study the long-term outcomes and evolving genetic changes in non-malignant blood diseases. Exploratory Objectives * Determine whether analysis of select patient-derived bone marrow hematopoietic progenitor/stem (HSPC) cells or induced pluripotent stem (iPS) cells can recapitulate genotype-phenotype relationships and provide insight into disease mechanisms. * Determine whether analysis of circulating mature blood cells and their progenitors from selected patients with suspected or proven genetic hematological disorders can recapitulate genotype-phenotype relationships and provide insight into disease mechanisms.
This is a Phase II trial to determine the ability of a reduced intensity conditioning regimen to allow successful engraftment with CD3+ /CD19+ depleted peripheral stem cell grafts from mismatched donors. There are two conditioning regimens depending upon patient diagnosis and age.
This study's goal is to determine the frequency and severity of acute graft versus host disease, to evaluate incidence of primary and secondary graft rejection, to assess event free survival and overall survival, to determine the time to neutrophil and platelet engraftment, to determine the time to immune reconstitution (including normalization of T, B and natural killer (NK) cell repertoire and Immunoglobulin G production), and to establish the incidence of infectious complications including bacterial, viral, fungal and atypical mycobacterial and other infections following CD34+ selection in children, adolescents and young adults receiving an allogeneic peripheral blood stem cell transplant from a family member or unrelated adult donor for a non-malignant disease.
Background: Clinical Genetics Branch (CGB) researchers study individuals and populations at high genetic risk of cancer in order to improve our understanding of cancer and to improve cancer care. There are currently 8 open clinical genetics studies at the CGB. * 001109: Defining the Natural History of Squamous Cell Carcinoma in Fanconi anemia (SCC Screening in FA). * 20C0107: Clinical, Genetic, and Epidemiologic Study of Children and Adults with RASopathies (RASopathies Study). * 02C0052: Etiologic Investigation of Cancer Susceptibility in Inherited Bone Marrow Failure Syndromes: A Natural History Study (Cancer in Bone Marrow Failure). * 11C0255: Clinical, Epidemiologic, and Genetic Studies of Li-Fraumeni Syndrome (Li Fraumeni Syndrome Study). * 11C0034: DICER1-Related Pleuropulmonary Blastoma Cancer Predisposition Syndrome: A Natural History Study (Pleuropulmonary Blastoma). * 02C0211: Clinical, Laboratory, and Epidemiologic Characterization of Individuals and Families at High Risk of Melanoma (Melanoma-Prone Families). * 78C0039: Clinical, Laboratory, and Epidemiologic Characterization of Individuals and Families at High Risk of Cancer (Cancer-prone families study). * 10CN188: Genetic Clues to Chordoma Etiology: A Protocol to Identify Sporadic Chordoma Patients for Studies of Cancer-susceptibility Genes (Sporadic Chordoma Study). Objective: To find people to participate in active CGB cancer research studies. Eligibility: People of any age who meet the eligibility criteria for one of the open CGB cancer research studies. This typically involves a personal or family history of certain cancers that are being studied by researchers at CGB. Design: Participants will fill out a screening questionnaire to determine if they are eligible to participate in one or more CGB clinical genetics studies. The survey asks about personal health history, including cancer; their family history; and genetic testing results and takes 15 to 20 minutes. Each study has its own eligibility criteria. Survey respondents will respond with study (or studies) that are interested in participating in, and the relevant study team(s) will review the screener to determine eligibility to participate in the study. Participants who are determine to be eligible for a study based on their screener will be contacted by the respective study team to learn more about the study and to consent to enroll in the study if they choose to do so. Participants who consent to enroll in a study will be asked to provide medical records and samples such as blood, saliva, or other tissues and to participate in activities such as phone interviews or surveys. They may be invited for evaluations at the clinical center. Every study activity is voluntary. None of the studies provide treatments. Participants may be contacted to consider enrolling in future studies.
Mucositis is a normal side effect of stem cell transplant which happens as a result of chemotherapy being given prior to a new donor cell infusion (bone marrow transplant). The chemotherapy will kill cancer cells, but good cells, such as those in the mouth, are killed too. The mouth cells going away causes the areas in the mouth to be blistered, irritated, sore, and extremely painful. Pain medication (usually morphine or hydromorphone if allergic to morphine) are given when oral blisters are seen or felt by patient in patient's mouth. However, one pain medication given through a vein in the patient may or may not be effective and providers are often challenged with providing good pain control while waiting for the new donor cells to grow, which will then heal the mouth. This is a period of waiting that is 6-8 weeks. The investigators know that methadone, a second pain medication, may decrease pain in a different way than morphine. This is because methadone works in a different way in the brain than morphine. By giving these pain medicines together, the hope of the study is to show decreased pain while waiting for new cells to grow. The goal of this clinical trial is to hope to learn whether adding methadone (second pain medication) to the current pain medication which is morphine alone (all patients will receive this pain medication) will help reduce the pain experience of participant. Current treatment of morphine alone is sometimes not entirely effective and so any improvement of pain while waiting for new cells to grow is one of the goals of this study. If methadone is effective in decreasing pain, then patients may benefit in the future from using these two medications up front when getting a transplant. Participant in this study between 6-18 years of age and is needing a stem cell transplant for a disease that can potentially be cured by transplantation. Participant in this study is receiving chemotherapy and/or radiation conditioning that can cause mucositis. Participants are being asked to participate in this study because participants meet criteria to receive methadone that may or may not reduce pain experience versus just being given morphine alone, which is what all patients are given when the participants have mucositis. The main goal of the study is to see if less opioid (pain medication) when methadone is added in comparison to participant who uses PCA only. The investigators also want to learn if patient's overall function is improved if given methadone. Another goal would be to see the number of TPN days the participant received and if the participant who was given methadone began to eat sooner. Other smaller goals include learning about side effects of methadone, and if the hospital stay is less for those who receive the study medication. This medication will be given at Children's Medical Center of Dallas while participant is admitted for the stem cell transplant. There is no sponsor that is funding the study and this drug will be given free of charge in exchange for participation in the study
The purpose of this study is to examine if it is feasible to administer decitabine and filgrastim after allogenic hematopoietic stem cell transplant (HCT) in children and young adults with myelodysplastic syndrome, acute myeloid leukemia and related myeloid disorders, and if the treatment is effective in preventing relapse after HCT. The names of the study drugs involved in this study are: * Decitabine (a nucleoside metabolic inhibitor) * Filgrastim (a recombinant granulocyte colony-stimulating factor (G-CSF)
Background: Fanconi anemia (FA) is an inherited disorder. People with FA are more likely to get certain cancers, especially squamous cell carcinoma (SCC). These cancers usually appear first in the mouth, esophagus, and genital and anal areas. Early detection of SCCs may help improve survival rates for people with FA. Objective: This natural history study will regularly screen people with FA for SCC. Eligibility: People aged 12 years and older with FA or a prior cancer diagnosis. Children aged 8 to 11 years with FA may also be eligible. Design: Participants will receive a comprehensive screening for cancer or early signs of cancer. Participants will have a physical exam. They will provide blood and saliva samples. Cells will be collected by rubbing a swab on the inside of the cheeks. A skin sample may be removed from the back, buttocks, or inside of the upper arm. Participants will have pictures taken of their mouth. Any mouth sores will be mapped. Cells will be collected from the sores with a small brush. Specialists will examine the participant s ears, nose, throat, teeth, and skin. Adult participants may have a gastrointestinal exam or pelvic exam. Participants may have an endoscopy. A long tube with a camera and a light will be inserted through the mouth and down into the stomach. Participants may have a liver ultrasound. A wand will be pressed against their belly to get pictures of the organs inside the body. Participants will have screenings every year for up to 10 years. Each visit will last up to 3 days. They will have remote follow-up visits every 6 - 8 months....
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.
This study is a prospective, single center phase II clinical trial in which patients with Severe Aplastic Anemia (SAA) ) will receive a haploidentical transplantation. The purpose of this study is to learn more about newer methods of transplanting blood forming cells donated by a family member that is not fully matched to the patient. This includes studying the effects of the chemotherapy, radiation, the transplanted cell product and additional white blood cell (lymphocyte) infusions on the patient's body, disease and overall survival. The primary objective is to assess the rate of engraftment at 30 days and overall survival (OS) and event free survival (EFS) at 1 year post-hematopoietic cell transplantation (HCT). Primary Objectives * To estimate the rate of engraftment at 30 days after TCR αβ+ T-cell-depleted graft infusion in patients receiving a single dose of post graft infusion cyclophosphamide. * To estimate the overall survival and event free survival at 1-year post transplantation. Secondary Objectives * To calculate the incidence of acute and chronic GVHD after HCT. * To calculate the rate of secondary graft rejection at 1-year post transplantation * To calculate the cumulative incidence of viral reactivation (CMV, EBV and adenovirus). * To describe the immune reconstitution after TCR αβ+ T-cell-depleted graft infusion at 1 month, 3 months, 6 months, 9 months, and 1 year. Exploratory Objectives * To longitudinally assess the phenotype and epigenetic profile of T-cells in SAA patients receiving HCT for SAA. * To assess the phenotype and epigenetic profile of T-cells in DLI administered to SAA patients post HCT. * To longitudinally assess CD8 T cell differentiation status in SAA patients using an epigenetic atlas of human CD8 T cell differentiation. * To examine the effector functions and proliferative capacity of CD8 T cells isolated from SAA patients before and after DLI. * Quantify donor derived Treg cells at different time points in patients received HCT. * Determine Treg activation status at different stages after HCT. * Are specific features of the DLI product associated with particular immune repertoire profiles post-transplant? * How does the diversity and functional profile of the DLI product alter the response to pathogens in the recipient? * Do baseline features of the recipient's innate and adaptive immune cells correlate with post-transplant immune repertoires and response profiles?
This is a data collection study that will examine the general diagnostic and treatment data associated with the reduced-intensity chemotherapy-based regimen paired with simple alemtuzumab dosing strata designed to prevented graft failure and to aid in immune reconstitution following hematopoietic stem cell transplantation.
This research is being done to learn if a new type of haploidentical transplantation using TCR alpha beta and CD19 depleted stem cell graft from the donor is safe and effective to treat the patient's underlying condition. This study will use stem cells obtained via peripheral blood or bone marrow from parent or other half-matched family member donor. These will be processed through a special device called CliniMACS, which is considered investigational.
This is a Phase II study of allogeneic hematopoietic stem cell transplant (HCT) using a myeloablative preparative regimen (of either total body irradiation (TBI); or, fludarabine/busulfan for patients unable to receive further radiation). followed by a post-transplant graft-versus-host disease (GVHD) prophylaxis regimen of post-transplant cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF).
The primary objective of this protocol is to expand access for patients who lack a fully HLA (Human leukocyte antigen) matched sibling donor, and who are candidates for allogeneic hematopoietic stem cell transplant (HSCT). These patients have a serious or immediately life-threatening disease for which HSCT is indicated. These patients are not eligible for other Children's Hospital of Philadelphia Institutional Review Board (IRB) approved protocols that utilize CliniMACs technology for T depletion.
This study is designed to estimate the efficacy and toxicity of familial HLA mismatched bone marrow transplants in patients with non-malignant disease who are less than 21 years of age and could benefit from the procedure.
This is a single arm pilot study using TCR alpha/beta+ T cell-depleted peripheral blood stem cells (PBSC) from closely matched unrelated donors or partially matched/haploidentical related donors for hematopoietic stem cell transplant (HSCT) in patients with acquired and inherited bone marrow failure (BMF) syndromes.
This clinical trial tests next generation sequencing (NGS) for the detection of precursor features of pre-myeloid cancers and bone marrow failure syndromes. NGS is a procedure that looks at relevant cancer associated genes and what they do. Finding genetic markers for pre-malignant conditions may help identify patients who are at risk of pre-myeloid cancers and bone marrow failure syndromes and lead to earlier intervention.