Clinical Research Directory

Allogeneic Hematopoietic Stem Cell Transplant for GATA2 Mutations

Background: \- GATA2 deficiency is a disease caused by mutations in the GATA2 gene. It can cause different types of leukemia and other diseases. Researchers want to see if a stem cell transplant can be used to treat this condition. A stem cell transplant will give stem cells from a matching donor (related or unrelated) to a recipient. It will allow the donor stem cells to produce healthy bone marrow and blood cells that will attack the recipient s cancer cells. Objectives: \- To see if stem cell transplants are successful at treating GATA2 mutations and related conditions. Eligibility: \- Recipients who are between 6 and 70 years of age and have GATA2 deficiency. Design: * All participants will be screened with a physical exam and medical history. Blood samples will be collected. Recipients will have imaging studies and other tests. * Recipients will have chemotherapy or radiation to prepare for the transplant. On the day of the transplant, they will receive the donated stem cells. * Recipients will stay in the hospital until their condition is stable after transplant. * Frequent blood tests and scans will be required for the first 6 months after the transplant, followed by less frequent visits over time.

GvHD Prophylaxis in Unrelated Donor HCT: Randomized Trial Comparing PTCY Versus ATG

Post-transplantation cyclophosphamide (PTCY) has become increasingly popular in the haploidentical HCT setting because it overcomes the HLA-mismatch barrier and levels GVHD risk. This advantage may also prove useful in the context of unrelated donor (UD) transplantation. GVHD prophylaxis for matched unrelated donor hematopoietic cell transplantation (alloHCT) in Europe is mainly conducted with ATG. Still, the burden of acute and chronic GVHD and especially of relapse remains high with both approaches for GVHD prevention. PTCY has not been tested against the current standard ATG for GvHD prophylaxis in large randomized trials. The goal of this trial is to compare the outcomes of PTCY and ATG for patients receiving unrelated donor PBSCT. PTCY-based prophylaxis promises to have beneficial net effects on immune reconstitution, GVHD and disease control, and thus might impact on patient survival.

Prospective Evaluation of Ivosidenib Maintenance Following Allogeneic Stem Cell Transplantation in Patients With Acute Myeloid Leukemia or High-risk Myelodysplastic Neoplasia With IDH1 (Isocitrate Dehydrogenase 1) Mutation

maintenance of AML or MDS patients with known IDH1 mutation after allogeneic stem cell transplantation within past 100 days

Eganelisib as Monotherapy and in Combination With Cytarabine in Relapsed/Refractory AML

This is a Phase 1b open-label, multicenter, dose-escalation and dose-optimization study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor efficacy of eganelisib as monotherapy and in combination with cytarabine in patients with relapsed/refractory (r/r) acute myeloid leukemia (AML) or r/r higher-risk myelodysplastic syndromes (HR-MDS). The study consists of 2 parts: * Part 1: Dose Escalation (DE) in both monotherapy and in combination. * Part 2: Dose Optimization

A Pilot Study to Evaluate the Feasibility of Post-Hematopoietic Stem Cell Transplant Prophylaxis With Decitabine Combined With Filgrastim for Children and Young Adults With AML, MDS and Related Myeloid Malignancies

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)

Pacritinib With Aza for Upfront Myelodysplastic Syndrome

This study will be conducted as a phase 1/2 study of safety and preliminary efficacy of pacritinib in combination with azacitidine for IPSS-M moderate low to very high risk MDS. Phase one will be a 3 + 3 design to assess the dose for the phase two portion. The phase two portion will employ a simon min-max two-stage design whereby fifteen patients will be enrolled in the first stage then ten more if at least two patients in stage one have a response. The dosing of pacritinib for the phase two study will be based on the phase one findings. Standard dosing of azacitidine will be used. A correlative study will be conducted in conjunction with the trial where the investigators will measure whole blood collected pre-treatment and at four days post-treatment to measure intracellular flow and phosflow to detect JAK/STAT, NF-κβ, and AKT/mTOR signaling in patient samples and how treatment affects these pathways.

Frailty Phenotype Assessments to Optimize Treatment Strategies for Older Patients With Hematologic Malignancies

The purpose of this research study is to determine if frailty assessments can be used to predict how well patients aged 60 years and older will do after chemotherapy, CAR T-cell therapy, or allogeneic stem cell transplant.

Global Registry and Natural History Study for Mitochondrial Disorders

The main goal of the project is provision of a global registry for mitochondrial disorders to harmonize previous national registries, enable world-wide participation and facilitate natural history studies, definition of outcome measures and conduction of clinical trials.

Comparison of ATLG and ATG for Immune Reconstitution After Allo-HSCT for Hematologic Malignancy

Allogeneic hematopoietic stem cell transplantation is the only curative treatment for malignant hematologic diseases. However, immune rejection is a major limitation in its application. In the "Beijing Protocol", the use of granulocyte colony-stimulating factor (G-CSF) in combination with anti-thymocyte globulin (ATG) can achieve "everyone has a donor". The use of ATG, however, can interfere with the recovery of immune function after transplantation, increasing the risk of life-threatening complications such as viral infections or graft-versus-host disease. Rabbit anti-human T-lymphocyte immunoglobulin (ATLG) is currently approved for the prevention of organ transplant rejection, which is produced differently from ATG. Previous studies have shown that transplant preconditioning with ATLG is effective in preventing graft-versus-host disease and even reduces the incidence of cytomegalovirus, etc. after transplantation. In this study, we will prospectively apply containing ATLG in a cohort of allogeneic hematopoietic stem cell transplantation for malignant hematologic diseases and dynamically observe the state of immune reconstitution of patients after transplantation. We will also compare it with a matched cohort of conventional combined ATGs during the same period to explore the impact of ATLG on immune reconstitution after transplantation.

A Study of T-Cell Receptor Engineered Donor T Cells in Subjects Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation

This is a multicenter, genetically-randomized, controlled, Phase 3 study evaluating the efficacy and safety of T-cell receptor-engineered donor T cells targeting HA-2 (TSC-101) administered following reduced-intensity conditioning (RIC) hematopoietic cell transplantation (HCT) in participants with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). The study will compare TSC-101 plus standard of care (SOC) versus SOC alone in participants undergoing allogeneic peripheral blood stem cell transplantation from haploidentical or mismatched unrelated donors.

A Phase 1/3 Study of T-Cell Receptor Engineered Donor T Cells in Subjects Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation

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, MMUD, or MUD

Familial Investigations of Childhood Cancer Predisposition

NOTE: This is a research study and is not meant to be a substitute for clinical genetic testing. Families may never receive results from the study or may receive results many years from the time they enroll. If you are interested in clinical testing please consider seeing a local genetic counselor or other genetics professional. If you have already had clinical genetic testing and meet eligibility criteria for this study as shown in the Eligibility Section, you may enroll regardless of the results of your clinical genetic testing. While it is well recognized that hereditary factors contribute to the development of a subset of human cancers, the cause for many cancers remains unknown. The application of next generation sequencing (NGS) technologies has expanded knowledge in the field of hereditary cancer predisposition. Currently, more than 100 cancer predisposing genes have been identified, and it is now estimated that approximately 10% of all cancer patients have an underlying genetic predisposition. The purpose of this protocol is to identify novel cancer predisposing genes and/or genetic variants. For this study, the investigators will establish a Data Registry linked to a Repository of biological samples. Health information, blood samples and occasionally leftover tumor samples will be collected from individuals with familial cancer. The investigators will use NGS approaches to find changes in genes that may be important in the development of familial cancer. The information gained from this study may provide new and better ways to diagnose and care for people with hereditary cancer. PRIMARY OBJECTIVE: * Establish a registry of families with clustering of cancer in which clinical data are linked to a repository of cryopreserved blood cells, germline DNA, and tumor tissues from the proband and other family members. SECONDARY OBJECTIVE: * Identify novel cancer predisposing genes and/or genetic variants in families with clustering of cancer for which the underlying genetic basis is unknown.

SHR2554/AZA + Overlapped Modified BUCY for High-risk/Relapsed Leukemia/MDS

This study was designed as a prospective, multicenter, open-label, randomized controlled trial. Eligible participants were patients aged 15-65 years with high risk or relapsed/refractory acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic neoplasms (MDS), diagnosed based on bone marrow morphology, immunophenotyping, genetic testing, and treatment response assessment. The experimental group received SHR2554 combined with azacitidine as an overlapped sequential combination with the mBuCy conditioning regimen, whereas the control group received the mBuCy conditioning regimen, both followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). The primary endpoint is 1-year event-free survival (EFS). Secondary endpoints include 2-year overall survival, 2-year cumulative incidence of relapse, transplant-related mortality, incidence of acute/chronic GVHD, and safety profiles.

Fedratinib in Myelodysplastic /Myeloproliferative Neoplasms (MDS/MPNs) and Chronic Neutrophilic Leukemia (CNL)

The purpose of the study is to evaluate the effectiveness, safety, and tolerability of a study drug called fedratinib in participants with myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) and chronic neutrophilic leukemia (CNL).

A Phase II Study of Vibecotamab (XmAb14045) for MRD- Positive AML and MDS After Hypomethylating Agent Failure

This is a phase II single-center study to evaluate the safety and effectiveness of vibecotamab, a CD3-CD123 bispecific antibody, in patients with acute myeloid leukemia with persistent or recurrent measurable residual disease and in patients with myelodysplastic syndrome that has not responded to or relapsed after conventional therapy

Pilot Study of CC 486 (Oral Azacitidine) Plus BSC as Maintenance After sc Azacitidine in Elderly HR-IPSS-R MDS Patients

Treatment of higher-risk (intermediate, high and very high) Myelodysplastic Syndromes (MDS) according to the revised International Prognostic Scoring System (IPSS-R) who obtained a stable hematological response ( CR, PR) after subcutaneous azacitidine treatment. Azacitidine is administered in hospital in a day care regimen, in Italy only by subcutaneous injection. The long duration of therapy obliges patients to travel to the hospital regularly, with evident worsening quality of life, both for patients and caregivers, although balanced by prolongation of survival and hematological improvement. Many patients stop therapy or are reluctant to continue because of the dependence from caregivers and hospital care. This clinical study will evaluate the efficacy and safety of oral azacitidine (CC-486) plus best supportive care in subjects with higher-risk (intermediate, high and very high) Myelodysplastic Syndrome (MDS) according to the revised International Prognostic Scoring System (IPSS-R) and (high and INT-2) according to IPSS who obtained a stable hematological response (CR, PR, SD with HI) after at least 4-6 cycles of subcutaneous azacitidine treatment and maintained for 2 additional cycles.

A Phase 1 Study With LYT-200 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML), or With Relapsed/Refractory, High-risk Myelodysplastic Syndrome (MDS)

A Phase 1 Open-label, Multi-center Study of the Safety, Pharmacokinetics (PK), and Anti-tumor Activity of LYT- 200 in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML), or with Relapsed/refractory, High-risk Myelodysplastic Syndrome (MDS)

Individual Molecular MRD Monitoring for MDS Patients After Allo-SCT

This study aims to develop highly sensitive methods for early detection of relapse based on the patients unique mutations. Initially, a mutational screen is being performed. Primers directed against these mutations will be constructed and presence of mutations will be followed in bone marrow and blood frequently after transplantation.

MT2025-35 Allogeneic Hematopoietic Stem Cell Transplantation Using Reduced Intensity Conditioning Treosulfan and Fludarabine, With Post-Transplant Cytoxan (PTCy) for the Treatment of Hematological Diseases

This is a Phase II study following subjects proceeding with Treosulfan (36g/m2) preparative regimen followed by a related, unrelated, or partially matched family donor stem cell infusion, with post-transplant cyclophosphamide (PTCy) at 40mg/kg, tacrolimus and MMF for GVHD prophylaxis.

Study Investigating Patient-Reported Outcomes in Lower-risk MDS Patients

PRO-RED is a prospective, longitudinal, and multicenter observational study. Enrolled patients will be followed for 6 months in at least monthly intervals in terms of their received red blood cell transfusions and routine myelodysplastic neoplasms (MDS)-associated clinical parameters. In addition, the participating subjects will be provided with a digital/mobile application covering a smartphone app or paper-based questionnaires to answer a set of quality of life (QoL) questions once a week. During routine visits in the clinical trials center performed by the treating physician (at least every month), patients will answer standardized questionnaires for the assessment of MDS-related QoL. Also, included patients will take a photo of fingernails/eyelids with their smartphone camera with the aim to further analyze these pictures in a way to potentially deduct correlated hemoglobin (Hb)-values. As a long term aim beyond the PRO-RED study, the data will serve as a training cohort for the development of an algorithm for image-based calculation of individual Hb levels.

A Study Comparing Haploidentical Hematopoietic Stem Cell Transplantations (HSCTs) From Young Non-first-degree and Older First-degree Donors in Hematological Malignancies

An open, multi-center, randomized trial comparing haploidentical HSCTs from young non-first-degree and older first-degree donors in hematological malignancies

BMT-06: Study of Intensity Modulated Total Marrow Irradiation (IM-TMI)

This study is being done to see if the addition of a targeted form of radiation to standard conditioning regimen will increase the amount of cancer cells that are killed off in the bone marrow and reduce the chances that your disease may return. This description is called Intensity Modulated Total Marrow Irradiation (IM-TMI).

Replacing Bone Marrow Diagnostics With Peripheral Blood Analysis in Cytopenia Patients

This observational, multi-center study aims to collect data in order to develop a novel, minimally invasive diagnostic tool for MDS based on peripheral blood profiling of circulating hematopoietic stem and progenitor cells (cHSPCs) using single-cell RNA sequencing and DNA sequencing.

Cord Blood Transplant in Children and Young Adults With Blood Cancers and Non-malignant Disorders

This is a single-arm study to investigate 1-year treatment related mortality (TRM) in patients with life threatening non-malignant and malignant hematologic disorders who do not have a matched related donor for allogeneic transplantation.