Clinical Research Directory

Stem Cell Transplantation for Participants With Germline RUNX1 Associated Blood Cancers

Background: Some blood cancers can be caused by germline variants (changes) in a person s RUNX1 gene. Germline variants are genetic inherited changes a person is born with. Stem cell transplants are used to treat many diseases including blood cancers. Stem cell transplantation for patients with germline RUNX1 mutation driven blood cancers is standard of care and available in most major medical centers. The difference with this transplantation protocol is that it is prospective, only available to participants with germline RUNX1 variants and designed to determine the extent to which tailoring chemotherapy and supportive care medication doses for each individual patient may improve outcomes compared to data derived from retrospective transplantation protocols for patients with RUNX1 varinats which is less accurate. Objective: The primary objective of this protocol is to determine how tailored doses of chemotherapy and supportive care medications may improve disease free survival as compared to historical/expected disease free survival. Eligibility: People aged 4 to 70 years with blood cancer caused by a RUNX1 gene mutation. Other participants are also needed: (1) stem cell donors; (2) relatives who do not have a mutation in the RUNX1 gene; and (3) healthy volunteers. Design: Participants with blood cancer will be screened during approximately 1-3 months before transplatation. They will have blood tests and tests of their heart and lung function. A sample of bone marrow may be taken. A flexible tube (central line) will be inserted into a vein in participants' chest or lower neck. This line will remain in place during the hospitalization and be used to draw blood and administer drugs. These lines are almost always transitioned to a peripherally inserted central catheter (PICC) line at the time of hospital discharge. Participants will be inpatient for 4 to 5 weeks. They will receive drugs to prepare their body for the stem cell transplant. Some may also receive radiation treatment. Other tests will include imaging scans. The stem cell transplant will be given through the central line. After discharge from the clinic, participants will have follow-up visits at least once per week for approximately 100 days. Then they will have follow-up clinic visits for 3 years. Donors, relatives, and healthy volunteers may provide samples of blood, stool, and saliva. Adults may also opt to provide samples of skin and bone marrow.

A Study of JNJ-95804306 for Relapsed or Refractory Hematological Malignancies

The purpose of Part 1 (Dose Escalation) of the study is to assess how safe and tolerable JNJ-95804306 is and to find out the most suitable dose (recommended phase 2 dose \[RP2D\]) of JNJ-95804306. The purpose of Part 2 (Dose Expansion) is to further assess the safety of JNJ-95804306 and determine the anti-tumor activity alone and/or when administered in addition to standard of care (SoC) therapy at the putative RP2D(s) regimens in participants with hematological malignancies (cancer that begins in blood-forming tissue, such as the bone marrow, or in the cells of the immune system). For US sites: The purpose of Part 1 (Dose Escalation) of the study is to assess how safe and tolerable JNJ-95804306 is and to find out the most suitable dose (recommended phase 2 dose \[RP2D\]) of JNJ-95804306. The purpose of Part 2 (Dose Expansion) is to further assess the safety of JNJ-95804306 and determine the anti-tumor activity alone at the putative RP2D(s) regimens in participants with hematological malignancies (cancer that begins in blood-forming tissue, such as the bone marrow, or in the cells of the immune system).

Collection of Tissue Specimens From Patients With Solid Tumors or Blood Disorders and Their HLA-Compatible Family Members

This study will collect biological samples for use in research experiments aimed at better understanding the clinical features of certain diseases. The specimens may be used to evaluate the effectiveness of known therapies, refine treatment approaches, identify potential new therapies, and explore opportunities for disease prevention. The following individuals 2 years of age or older may be eligible for this study: * Patients with a cancerous solid tumor or a cancerous or non-cancerous blood disorder who are being screened for or who are enrolled in a treatment study at the NIH Clinical Center * HLA-compatible donor family members (18 years of age or older) of the above patients who are being evaluated for or are enrolled in an NIH study as a stem cell transplant donor * Patients with a cancerous solid tumor or a cancerous or non-cancerous blood disorder or a bone marrow failure condition who cannot participate in an NIH treatment protocol or travel to the NIH Clinical Center and who are referred for participation through their home health care provider. Research samples will be collected from participants when blood is drawn or bone marrow, urine, or stool is collected, or tumor or other tissue is biopsied as part of their general medical care. Investigators may periodically request an additional sample of blood, stool, or urine. Participants who are 18 years of age or older may donate a large number of white blood cells through a procedure called leukapheresis. This procedure is not part of general medical care and would be done for research purposes only. For apheresis, a catheter (plastic tube) is placed in a vein in the subject's arm. Blood flows from the vein into a cell separator machine, where the white cells are separated from the red cells, platelets, and plasma by a spinning process. The white cells are removed and collected, and the rest of the blood is returned to the subject through a second tube placed in the other arm.

Studyof Allogeneic Hematopoietic Stem Cell Transplantation From One Haplotype Mismatch Related Donor or From an Unrelated Donor in Elderly Patients

Allogeneic (Allo) hematopoietic stem cell transplantation (HSCT) is a recognized curative procedure for hematological malignancies. It is now well known that this property is related to the graft-versus-tumor (GVT) effect developed from the immunocompetent cells contained in or generating from the donor graft. For years, however, and despite this unique antitumoral activity, Allo-HSCT has been restricted to a limited number of patients due to two major limitations: the toxicity of the procedure and the absence of a donor for every single patients. More recently the stage has dramatically changed with respect to these two restraints. Over the last decade, many studies have established the feasibility of Allo-HSCT in older patients but the availability of MRD is even less frequent in elderlies, likely related to medical contraindication for graft donation or sibling deaths. UD are routinely used but associated with a high incidence of GVHD. As compared to younger populations, unrelated cord-blood HSCT is seldom performed in this population and numbers decrease with age due to the feared risk of supposed increased lethal infectious complications related to the effect of the delayed immune reconstitution in elderlies. Thus the need for alternative donors allowing for a safe and efficient transplantation is still unmet. In consequence, overall, despite the fact that Allo-HSCT feasibility has been established in the oldest patients, all these lacks contribute eventually to maintain a low rate of allo-HSCT performed in a population with the higher incidence of hematologic malignancies that usually present with the poorest prognosis. Thus it is critical developing innovative efficient therapeutic strategies answering this unmet-medical need. In this perspective, Haplo-HSCT could represent a part of the answer in this aged population. It offers the potential advantage to offer a rapid donor determination for virtually every single patient. In addition, our data suggest that in elderlies haplo-HSCT using T-repleted graft, RIC and PT-HDCy presents low NRM and retains an antitumor effect despite low GVHD incidences. They also suggest that haplo-HSCT may conduct to better outcome than URD-HSCT as an alternative to MRD-HSCT. It may also be associated with lower costs (no graft purchase and low post-transplant complications rate) and better QOL likely related to low cGVHD-rate. In addition the conduct of such trial at a time when the diffusion of the strategy in this population is just starting is really crucial before widespread uncontrolled dissemination. The investigators propose to address this question by prospectively comparing these 2 strategies in elderly patients without MRD, in terms of efficacy, safety and including the prospective evaluation study of quality-of-life (QOL). They will conduct a national, multicenter, open-label, comparative, randomized phase III trial in patients with hematological malignancies justifying an allo-HSCT from an alternative donor when a MRD has not been identified. When MRD search is recognized to be a failure, patients will be included in the clinical trial after informed consent and randomized in the two strategies based on donor search: * Reference group: Unrelated Donor group * Investigational group: Haplo Donor Group Investigators will use a composite end-point embracing the three main causes of failure: death, relapse and severe cGVHD (as a surrogate endpoint for QOL). We will analyze the HSCT usual objectives as GHVD, NRM, relapse and survival. A specific study of patients' health related quality of life will also be conducted using the FACT-BMT questionnaire. In addition, the success of the two strategies in term of transplant completion (donor determination, transplant realization and time to do so) will be compared.

Donor Lymphocyte Infusion After Allogeneic Hematopoietic Cell Transplantation for High-Risk Hematologic Malignancies

Background: People with blood cancers often receive blood or bone marrow transplants. But even with these treatments, the risk of relapse is high. Researchers want to see if giving the transplant recipient an infusion of lymphocytes (a type of white blood cell) from their transplant donor early after the transplant can reduce that risk. Objective: To learn if giving donor lymphocytes early after a transplant will help reduce the risk of relapse for people with certain blood cancers. Eligibility: Adults aged 18-65 with high-risk leukemia, lymphoma, myelodysplastic syndrome, or multiple myeloma that does not respond well to standard treatments and/or has a high risk of relapse. Healthy potential bone marrow and lymphocyte donor relatives aged 12 and older are also needed. Design: Participants will be screened with: Physical exam Blood and urine tests Spinal tap Eye exam Dental exam Heart and lung tests Imaging scans. A radioactive substance may be injected in their arm if a PET scan is needed. Bone marrow aspiration and biopsy Some screening tests will be repeated during the study. Participants will stay at the NIH hospital for about 4 weeks. They will receive a central venous catheter. They will get chemotherapy and other drugs starting 6 days before transplant. Then they will have their transplant. They will receive donor white blood cells 7 days later. They will give blood, bone marrow, urine, and stool samples for research. They must stay near NIH for at least 100 days after transplant. Participants will have periodic follow-up visits for 5 years. Healthy donors will have 2-3 visits. They will give blood, bone marrow, white blood cells, and stool samples for research. Participation will last for 5 years....

Phase I/II Study to Reduce Post-transplantation Cyclophosphamide Dosing for Older or Unfit Patients Undergoing Bone Marrow Transplantation for Hematologic Malignancies

Background: Certain blood cancers can be treated with blood or bone marrow transplants. Sometimes the donor cells attack the recipient's body, called graft-versus-host disease (GVHD). The chemotherapy drug cyclophosphamide helps reduce the risk and severity of GVHD. Researchers want to learn if using a lower dose of cyclophosphamide may reduce the drug's side effects while maintaining its effectiveness. Such an approach is being used in an ongoing clinical study at the NIH with promising results, but this approach has not been tested for transplants using lower doses of chemotherapy/radiation prior to the transplant. Objective: To learn if using a lower dose of cyclophosphamide will help people have a successful transplant and have fewer problems and side effects. Eligibility: Adults ages 18-85 who have a blood cancer that did not respond well to standard treatments or is at high risk for relapse without transplant, and their donors. Design: Participants may be screened with the following: Medical history Physical exam Blood and urine tests Heart and lung tests Body imaging scans (they may get a contrast agent) Spinal tap Bone marrow biopsy Participants will be hospitalized for 4-6 weeks. They will have a central venous catheter placed in a chest or neck vein. It will be used to give medicines, transfusions, and the donor cells, and to take blood. In the week before transplant, they will get 2 chemotherapy drugs and radiation. After the transplant, they will get the study drug for 2 days. They will take other drugs for up to 2 months. Participants must stay near NIH for 3 months after discharge for weekly study visits. Then they will have visits every 3-12 months until 5 years after transplant. Participants and donors will give blood, bone marrow, saliva, cheek swab, urine, and stool samples for research.

Phase I Trial Integrating HLA-Haploidentical Anti-CD19 CAR-T Cells With Post-Transplantation Cyclophosphamide-Based HLA-Haploidentical Hematopoietic Cell Transplantation

Background: High-risk blood cancers (leukemias and lymphomas) often come back after treatment, and many cannot be cured with chemotherapy alone. These cancers may be treated and potentially cured in 2 ways: (1) Bone marrow transplant (allogeneic hematopoietic cell transplantation, or alloHCT) gives immune and blood stem cells from a donor. These new cells can attack the cancer and also grow into healthy blood. (2) Chimeric antigen receptor (CAR) T-cell therapy takes immune cells and changes them in a lab to better recognize and target certain cancers. But these 2 treatments are not usually given at the same time. Objective: To test alloHCT and CAR-T cell therapy, used together, in people with high-risk blood cancers. Eligibility: People aged 18 to 75 years with an aggressive blood cancer that has a protein on the surface called CD19. A healthy related donor aged 12 years or older is also needed; this donor may be a parent or child or may be some siblings or even extended family members, but has to be half-matched at something called the HLA (human leukocyte antigen). Design: Participants will be screened. They will have imaging scans, blood tests, and tests of their heart and lung function. They will have eye and dental exams. They may have fluid drawn from around their spinal cord (spinal tap) and tissue taken from inside a bone (bone marrow biopsy). Healthy donors will provide bone marrow, immune cells, and about 9 tablespoons of blood for both the recipient s treatment and for research. They will also provide stool, saliva, and oral swabs just for research. Recipient participants will stay in the hospital for 4 to 6 weeks. They will be given drugs over 6 days to prepare for the cell therapies. Both the donor bone marrow cells and CAR-T-cells will be given through a tube inserted into a vein. They will receive drugs to reduce complications after the treatments. Participants will remain within a 1-hour drive of the hospital for 2 to 3 months after they leave the hospital. They will have frequent visits during that time. They will continue to have periodic follow-up visits for 5 years. ...

Animal-Assisted Intervention for Children With Cancer and Their Siblings

This study examined an animal-assisted program for children with hematologic or oncologic disease and their siblings. The program included ten weekly sessions involving dogs and donkeys. Children allocated to the program were compared with children on a waiting list. Assessments were conducted before the program, approximately 15 days after the last session, and approximately two months after the last session. The study assessed children's reported life events, emotional indicators in human figure drawings, family relationships, and parents' coping styles. Waiting-list participants were offered the program after their own final follow-up assessment. This study is being registered retrospectively, after study completion and analysis.

Effects of Synbiotic Supplementation on Gastrointestinal Symptoms, Appetite, and Nutritional Recovery in Patients After Autologous Bone Marrow Transplant

Patients undergoing autologous bone marrow transplantation (ABMT) receive high-dose chemotherapy and routine prophylactic antibiotics, which often disrupt the gut microbiome (dysbiosis). This imbalance can lead to debilitating gastrointestinal complications, loss of appetite, decreased dietary intake, and malnutrition, impairing recovery. The purpose of this randomized controlled trial is to evaluate whether daily supplementation with a tri-component synbiotic (combining multispecies probiotics, xylo-oligosaccharide prebiotics, and a tributyrin postbiotic) can improve gastrointestinal symptoms, appetite, and nutritional status in adult hematological cancer patients following autologous bone marrow transplantation. Participants will be randomly assigned (1:1 ratio) to either: 1. Control Group: Receiving standard post-transplant nutritional care based on clinical guidelines. 2. Intervention Group: Receiving the same standard nutritional care plus a daily oral synbiotic capsule for 3 months. Participants will be followed during the 3-month intervention period and for an additional 1-month post-intervention follow-up phase to assess the sustainability of benefits. The study will evaluate digestive symptoms, self-reported appetite, dietary intake, body weight, inflammatory markers (fecal calprotectin), and protein status (serum albumin), while closely monitoring participant safety.

Phase II Study of ZIO-101 in Advanced Blood and Bone Marrow Cancers

The study of safety of a new organic arsenic compound in the treatment of hematological malignancies.

Influenza Vaccination Strategy for Patients With Hematologic Malignancy

This randomized controlled trial evaluates and compares the immunogenicity of three different influenza vaccine formulations: high-dose trivalent (HD-IIV3), MF59-adjuvanted quadrivalent (aIIV4), and standard-dose trivalent (SD-IIV3) vaccines. The study population consists of patients with hematologic malignancies, including those undergoing autologous stem cell transplantation or CAR-T cell therapy. The primary goal is to identify which vaccine strategy elicits the most robust antibody and T cell-mediated immune responses in this severely immunocompromised population

Musculoskeletal Ultrasound in Patients With Hematologic Malignancies

This study evaluates the role and diagnostic value of musculoskeletal ultrasonography (MSUS) in adult patients with hematologic malignancies who present with musculoskeletal symptoms. Hematologic malignancies (such as leukemia, lymphoma, and multiple myeloma) frequently involve the musculoskeletal system through bone marrow infiltration, bone destruction, or soft-tissue lesions. Musculoskeletal ultrasound is a non-invasive, radiation-free, and high-resolution imaging technique that allows real-time evaluation of joints, muscles, tendons, bursae, and superficial bone changes. In this study, adult participants with confirmed blood cancers presenting with symptoms such as localized bone pain, joint swelling, muscle pain, or soft-tissue swelling will undergo a dedicated ultrasound examination of symptomatic areas. The study aims to characterize the patterns of musculoskeletal involvement (including cortical breaks, periosteal changes, soft-tissue masses, synovitis, and vascularity on Doppler imaging) and determine how these findings correlate with disease type, clinical presentation, and laboratory parameters.

Comparison of Hemanext ONE® System and Conventional Red Blood Cell Transfusion

The overall objective of this study is to collect preliminary effectiveness and safety data on the transfusion of hypoxic RBCs, manufactured with the Hemanext ONE device, in patients with hematological malignancies. The Hemanext ONE device received CE mark in April 2021 and marketing authorization through the FDA De Novo process in September 2023.

A Phase 1/2 Study of KK2430 in Participants With Hematologic Neoplasms

KK2430 ("Study Drug") as a potential treatment for people with Hematologic Neoplasms. KK2430 is an experimental drug; it has not been approved for the treatment of any disease by health authorities such as United States Food and Drug Administration (FDA), and this is the first time it will be given to people. The purpose of this Study is to find out more information about KK2430, whether it is safe in humans, how the body processes it, and if it works for treating your condition.

Fludarabine and Total Body Irradiation 800 Centigray (cGy) or 1125 cGy For Allogeneic Stem Cell Transplant Using Graft Versus Host Disease Prophylaxis With Post-Transplant Cyclophosphamide and Tacrolimus, Without Mycophenolate Mofetil

This is a pilot study to evaluate the feasibility, safety and potential benefits of removing one immune suppressive drug called mycophenolate mofetil (MMF) from the standard allogenic stem cell transplant treatment protocol. MMF will be omitted from the transplant regimen in 60 eligible patients with hematologic malignancies. Participants will be followed for up to 2 years post standard of care transplant at Cedars-Sinai.

Ceftazidime-Avibactam PK/PD and Resistance in Hematology Patients

This is a prospective, single-arm, observational, exploratory clinical study to evaluate whether the standard fixed dose of ceftazidime-avibactam (CAZ-AVI) achieves sufficient drug exposure (pharmacokinetic/pharmacodynamic, or PK/PD targets) in patients with blood cancers (or those undergoing stem cell transplantation). Patients with hematological malignancies are at high risk for severe, drug-resistant Gram-negative bacterial infections due to weakened immune systems. CAZ-AVI is a critical antibiotic used to treat these infections. However, there is limited evidence on whether the standard recommended dose achieves adequate drug concentrations for both ceftazidime and avibactam simultaneously in this specific patient group, and whether low drug exposure drives the development of antibiotic resistance during treatment. This study will enroll 60 participants who are already prescribed CAZ-AVI by their treating physicians based on routine clinical needs. The study will not change or interfere with any clinical treatment decisions. To measure drug levels, 5 small blood samples (about 2-3 mL each) will be collected within one dosing interval after the drug reaches a steady level in the body (typically 48 to 72 hours after starting treatment). Microbiological samples (such as blood cultures or swabs) will also be collected at multiple time points to monitor bacterial clearance and detect any newly developed resistance. Participants will be followed up for clinical outcomes and survival status up to 30 days after the completion of treatment. The primary goal of this study is to determine the percentage of patients who achieve the target drug exposure for both ceftazidime and avibactam simultaneously. The secondary goals are to observe clinical cure rates, bacterial clearance rates, 30-day survival, and the rate of newly induced antibiotic resistance during therapy.

Anti-CD25 Monoclonal Antibody for Prevention of Acute GVHD After Haploidentical HSCT

Acute graft-versus-host disease remains a major complication after haploidentical hematopoietic stem cell transplantation. Methotrexate is commonly used as part of graft-versus-host disease prophylaxis, but it may be associated with delayed hematopoietic recovery and transplant-related toxicities, including oral mucositis. This is a prospective, multicenter, randomized, open-label, parallel-controlled Phase III clinical trial designed to evaluate an anti-CD25 monoclonal antibody regimen compared with methotrexate for the prevention of acute graft-versus-host disease after haploidentical hematopoietic stem cell transplantation. Eligible patients with hematologic malignancies scheduled to undergo haploidentical allogeneic hematopoietic stem cell transplantation will be randomly assigned in a 1:1 ratio to receive either methotrexate-based prophylaxis or anti-CD25 monoclonal antibody-based prophylaxis, in combination with standard graft-versus-host disease prophylaxis including anti-thymocyte globulin, calcineurin inhibitor, and mycophenolate mofetil. The primary objective is to compare 12-month graft-versus-host disease-free, relapse-free survival between the two groups. Secondary objectives include comparison of acute graft-versus-host disease, chronic graft-versus-host disease, oral mucositis, hematopoietic recovery, cytomegalovirus and Epstein-Barr virus reactivation, infection, relapse, non-relapse mortality, overall survival, and leukemia-free survival.

Take5Care+: A Self-management Educational Intervention

Patients who are diagnosed with haematological malignancies may feel that they have little or no control over their health which can be distressing. However, a diagnosis can also be the opportunity for a "teachable moment" during which patients are more likely to open to behaviour change, which can positively impact on their health and wellbeing. Take Five to Age Well (Take Five) was designed to empower people to achieve effective, long-term self-management of health by introducing healthy habits in 30 days. In collaboration with Northampton General Hospital (NGH) the current study will recruit newly diagnosed haematology patients who are either being actively monitored or only on non-intensive treatment to take part in a self-managed behaviour change intervention. This is primarily a feasibility study to inform main trials in the future. The main aim of the research is: 1. To assess the feasibility of using Take5Care+ with patients newly diagnosed with indolent or chronic haematological malignancies, recruited via hospital departments There are also secondary aims, including: 2. To assess the impact of participating in Take5Care+ on patients' self-reported health and well-being, healthy behaviours and sense of control, knowledge and management of health 3. To explore the perceptions of patients and clinicians about their participation in the Take5Care+ Patients who wish to take part will be asked to fill out a survey at baseline, complete a "challenge" where they commit to a healthy action for 30 days, fill out a second survey immediately after and a third survey three months later. Patients may also consent to participating in an interview post-challenge. Giving consent and completing the baseline survey will take place in NGH but the challenge is self-managed at home and remotely supported. Survey 2, Survey 3 and the optional interviews are also carried out online or over the phone.

Cognitive Training Intervention and Attitudes Towards Genetics

A pilot study to evaluate feasibility of enrollment of patients in an intervention to improve neurocognitive function in hematopoietic cell transplantation (HCT) survivors using the cognitive training Lumosity program. In addition, patients' interest in receiving information regarding genetic risk of cognitive impairment post-HCT will be measured.

LLM-Generated Plain-Language Patient Synopses to Improve Comprehension in Hematology and Oncology (oncOPAL)

This study tests whether patients with blood cancer or other cancers better understand their medical information when it is rewritten in plain language by an artificial intelligence (AI) system. When patients are discharged from the hospital, they receive a medical letter summarizing their diagnosis, treatment, and next steps. These letters are often written in technical language that is difficult for patients to understand. In this study, an AI language model running on the hospital's own secure servers rewrites parts of this letter into simpler language. A physician checks the simplified version before the patient receives it. Patients are randomly assigned to one of two groups. One group receives both the standard medical letter and the AI-simplified version. The other group receives the standard letter only. A separate group of patients who do not speak German well will receive a simplified and translated version. After reading their letter, all participants fill out a short questionnaire about how well they understood the information. The study takes place at TUM University Hospital (Klinikum rechts der Isar) in Munich, Germany.

Mind-body Medicine for Patients With Malignant Hematological Diseases

This randomized controlled trial aims to investigate the effectiveness of a mind-body group program as a supprtivemanagement strategy for fatigue in patients with malignant hematological diseases.

UWCCC Molecular Tumor Board Registry

This study seeks to evaluate the clinical utility of the Precision Medicine Molecular Tumor Board, and to track patient outcomes.

Pre-myeloid Cancer and Bone Marrow Failure Clinic Study

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.

Platelet Transfusions in Hematopoietic Stem Cell Transplantation (The PATH III Trial)

It is hypothesized that a strategy using prophylactic oral and intravenous Tranexamic Acid (TXA) with therapeutic platelet transfusions (if required) is safe and more effective than prophylactic platelet transfusions in patients undergoing an autologous hematopoietic stem cell transplantation (ASCT).