Hematologic Malignancy

During the last decades hematologists have excelled at improving and refining the classification, diagnosis, and thus ultimately the therapeutic decision-making process for their patients. This continuous evolution proceeded in parallel to seminal discoveries in basic science such as FISH, PCR and NGS. So far, the current WHO classification serves as reference to diagnostic decision making and is largely based on 5 diagnostic pillars: cytomorphology of peripheral blood and/or bone marrow smears, histology and immunohistochemistry of bone marrow trephine biopsies or lymph nodes, immunophenotyping, chromosome banding analysis supplemented by FISH analysis, molecular genetics including PCR and targeted panel sequencing via NGS. This leads to a swift diagnosis in 90 % of all cases. The leftover 10 % remain a challenge for hematopathologists and clinicians alike and are resolved through interdisciplinary teams in the context of specialized boards. With the advent of high throughput sequencing (mainly WGS and WTS) the possibility of a comprehensive and detailed portrait of the genetic alterations - specifically in challenging cases - has become a realistic alternative to classical methods. In SIRIUS the investigators will prospectively challenge this hypothesis to address the question of how often a better or final diagnosis can be delivered by WGS and/or WTS and if unclear cases can be efficiently resolved.

To the best of our knowledge, BELUGA will be the first prospective trial investigating the usefulness of deep learning-based hematologic diagnostic algorithms. Taking advantage of an unprecedented collection of diagnostic samples consisting of flow cytometry datapoints and digitalized blood-smears, categorization of yet undiagnosed patient samples will prospectively be compared to current state-of-the-art diagnosis at the Munich Leukemia Laboratory (hereafter MLL). In total, a collection of 25,000 digitalized blood smears and 25,000 flow cytometry datapoints will be prospectively used to train an AI-based deep neuronal network for correct categorization. Subsequently, the superiority will be challenged for the primary endpoints: sensitivity and specificity of diagnosis, most probable diagnosis, and time to diagnose. The secondary endpoints will compare the consequences regarding further diagnostic work-up and, thus, clinical decision making between routine diagnosis and AI guided diagnostics. BELUGA will set the stage for the introduction of AI-based hematologic diagnostics in a real-world setting.

The aim of this study is to determine the effectiveness of DCog Short, a self-reporting, iPad-based application tool, in assessing neurotoxicity in participants undergoing CAR-T cell therapy.

This research is being done to investigate the safety and effectiveness of Darzalex Faspro (daratumumab and hyaluronidase-fihj) (a monoclonal antibody that targets plasma cells that make antibodies) and whether it can lower donor specific antibodies (DSA) levels to low enough levels to permit patients to proceed with allogeneic peripheral blood transplant (alloBMT). Those being asked to participate have high DSA levels that puts those being asked to participate at high risk of rejecting the available donor's blood stem cells and making those being asked to participate ineligible to receive a stem cell transplant.

The use of venetoclax-based therapies for pediatric patients with relapsed or refractory malignancies is increasingly common outside of the clinical trial setting. For patients who cannot swallow tablets, it is common to crush the tablets and dissolve them in liquid to create a solution. However, no PK data exists in adults or children using crushed tablets dissolved in liquid in this manner, and as a result, the venetoclax exposure with this solution is unknown. Primary Objectives • To determine the pharmacokinetics of venetoclax when commercially available tablets are crushed and dissolved into a solution Secondary Objectives * To evaluate the safety of crushed venetoclax tablets administered as an oral solution * To determine the pharmacokinetics of venetoclax solution in patients receiving concomitant strong and moderate CYP3A inhibitors * To determine potential pharmacokinetic differences based on route of venetoclax solution administration (ie. PO vs NG tube vs G-tube) * To determine the concentration of venetoclax in cerebral spinal fluid when administered as an oral solution

Prospective, multi-center open label study of HLA-partially to fully matched allogeneic cryopreserved deceased donor bone marrow transplantation and living donor transplantation for patients with hematologic malignancies.

The purpose of this study is to learn more about newer methods of transplanting blood cells donated by a partially matched family member to children with high-risk CD19 positive leukemia ALL. Primary Objective: \- To assess the safety and feasibility of combining CD19-CAR(Mem) T cells after TCRαβ+/CD19 depleted haploidentical donor transplantation for pediatric patients with relapsed/refractory CD19+ B-cell malignancies. Secondary Objectives: * To estimate 1-year post-transplant overall survival, event-free survival, and GVHD-free relapse-free survival (GRFS). * To estimate cumulative incidence of engraftment, acute and chronic GVHD, and immune-related adverse events, including CRS and ICANS.

The safety, tolerability, and antileukemic response of ziftomenib in combination with standard of care treatments for patients with relapsed/refractory acute myeloid leukemia will be examined with the following agents: FLAG-IDA, low-dose cytarabine, and gilteritinib.

This research study is creating a way to collect and store specimens and information from participants who may be at an increased risk of developing cancer, or has been diagnosed with an early phase of a cancer or a family member who has a family member with a precursor condition for cancer. * The objective of this study is to identify exposures as well as clinical, molecular, and pathological changes that can be used to predict early development of cancer, malignant transformation, and risks of progression to symptomatic cancer that can ultimately be fatal. * The ultimate goal is to identify novel markers of early detection and risk stratification to drive potential therapeutic approaches to intercept progression to cancer.

This is an open-labelled and non-controlled Phase I/II clinical trial, evaluating the safety and the efficacy of Human T Lymphoid Progenitor (HTLP) injection to accelerate immune reconstitution after umbilical cord blood (UCB) transplantation in adult patients with hematologic malignancies. The dose limiting toxicity of HTLP injection will be evaluated using a model-based design.

The study is designed to examine the feasibility and safety of collecting autologous hematopoietic stem cells (HSCs) to be combined with CAR T-cell therapy for patients with relapsed/refractory (r/r) hematological disease. The study will evaluate feasibility of collecting the target dose of HSCs from at least 50% of enrolled patients. The study will assess safety based on incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in the first 60 days post CAR T dosing, and also through the collection of adverse events (AEs) and serious adverse events (SAEs) as well as the durability of response after treatment with HSCs with CAR T. The study follows an open-label, single-center and single non-randomized cohort design. 20 subjects with r/r hematological malignancies will be enrolled and treated to evaluate the feasibility and preliminary safety of collecting autologous HSCs and combining them with CAR T-cell therapy.

The goal of this clinical trial is to learn if using an intervention website (Mosaic) improves selected patient-reported outcomes in adult blood cancer patients undergoing allogeneic or autologous stem cell transplant, compared to using an educational website (control group). Patients will be recruited prior to their scheduled transplant, then randomized to use one of these two study websites throughout the study. They will complete five assessments during the study: one before transplant (baseline) and four after transplant (2, 4, 6, and 8 month follow-ups). The main questions this trial aims to answer are: 1. Compared to patients using the control group website, do patients using the intervention website report greater improvements in general psychological distress, cancer treatment-related distress, physical symptoms, and health-related quality of life? 2. Are these benefits at least partially explained by improvements in perceived preparedness, self-efficacy, and approach coping and/or reductions in avoidant coping and perceived stress? 3. Do some patients benefit more from using the intervention website than others? Specifically, we will examine whether patients' primary language (English/Spanish) and their initial psychological distress are related to the benefit they get from using the intervention website. We will also explore effects of sex, race, ethnicity, and transplant type.

The purpose of this research study is to see if a virtual reality (VR) headset is useful in reducing physical discomfort and anxiety experienced by patients who are scheduled to undergo a bone marrow biopsy (BMB) and/or bone marrow aspiration (BMA).

People with hematologic cancer often have sleep disturbance and symptoms of fatigue, stress, and pain. This study is being done to test a mindfulness intervention for sleep disturbance and symptom management in patients with hematologic cancer during and after inpatient treatment (Nite2Day+). Participants will complete a baseline survey online, using a mobile application, or paper/pencil. Once the baseline survey is complete, participants will be randomized (like a flip of a coin) to receive Nite2Day+ or Standard Care. Nite2Day+ will include activities during and after inpatient treatment. During inpatient treatment, participants will use a mobile app to access: 1) mindfulness meditations, 2) brief sleep education videos, and 3) brief videos teaching strategies to improve sleep quality in the hospital. After inpatient treatment, participants will complete 6, videoconference sessions (45-60 minutes) with a trained therapist to learn mindfulness and behavioral coping strategies to self-manage nighttime sleep disturbance and daytime symptoms of fatigue, stress, and pain. Three follow-up surveys will occur at hospital discharge, and approximately 8, and 12 weeks after hospital discharge. Participants randomized to Nite2Day+ will be given the option to complete an exit interview to provide feedback on the Nite2Day+ program. Participants randomized to Standard Care will only complete the four surveys. All participants will continue to receive their usual medical care. The total study duration is about 16 weeks.

The goal of this study is to evaluate the effectiveness and usability of a newly developed oral anticancer agent adherence program implemented across 6 cancer clinics (two academic, two urban, and two rural). The study will include 160 adult participants with either solid tumors or hematologic malignancies who have been taking oral anticancer agents for at least six months. This study will have two groups of participants, a pre- and post-implementation group. In the pre-implementation of the program group, investigators will administer a survey to the 80 participants and gather information about their medication prior to their enrollment of the program. Similarly, 80 participants who have been enrolled into this program for at least 6 months will serve as the post-implementation group. These patients will be administered the same survey. The results from both groups will be analyzed to see how effective the medication adherence program is.

The purpose of this study is to find out whether adding belumosudil to a usual approach for reducing the risk of graft-versus-host disease (GVHD) may be an effective GVHD prevention approach for people with blood cancer who have a stem cell transplant. The investigators will also look at the safety of the study approach.

This is a comparative interventional study to determine the best way to prevent G-CSF induced bone pain in patients with hematological malignancies (blood cancers). G-CSF (Granulocyte Colony-Stimulating Factor) is a drug commonly used in these patients to boost white blood cell production, but it frequently causes severe bone pain. The study is comparing two oral medications for their effectiveness as a preventive treatment: * Diosmin-Hesperidin (a flavonoid supplement). * Loratadine (a common anti-allergy medication). The core question the study is trying to answer is: * Is diosmin-hesperidin effective in preventing G-CSF-induced bone pain compared to loratadine? * Does the combination of diosmin-hesperidin and loratadine offer better pain prevention than either drug alone?

The goal of this clinical trial is to learn whether giving patients a special type of donor immune cells (called CD45RA Depleted DLI) can help prevent viral infections after a stem cell transplant. It will also learn about the safety of this treatment. The main questions it aims to answer are: Does this treatment lower the chance of getting serious viral infections after transplant? What medical problems do patients have when receiving this treatment?

The goal of this clinical trial is to learn whether giving patients special donor immune cells (called "CD45RA Depleted DLI") can help treat viral infections that have not improved with standard antiviral drugs. These infections occur after a stem cell transplant. The study will also look at the safety of this treatment.

Prospective Cohort Study of clinical and laboratory data of patients with hemopathy.

This study is being done to learn more about the short-term and long-term side effects of CAR-T cell therapy. Specifically, researchers want to know how often patients get infections, have delays in recovering blood cell counts and/or have damage to the nervous system.

The overall goal of the RENEW-IN intervention is to assess the impact of a BL allergy delabeling intervention on antibiotic use and clinical outcomes in patients with a hematologic malignancy.

Influenza infection occurring during oncologic treatment or following hematopoietic cell transplantation (HCT) is associated with increased risk of morbidity in the form of lower respiratory tract infection (LRTI) and mortality relative to otherwise healthy patients. The study participants have been diagnosed with a hematological malignancy and are eligible to receive the current seasonal influenza (Flu) vaccine. Primary Objective * To determine the feasibility of opening a longitudinal prospective study of IIV immunogenicity in pediatric leukemia patients. * To describe the immunogenicity, as measured by the development of cell- and/or antibody-mediated influenza specific responses 3 to 5 weeks following vaccination, in a cohort of pediatric leukemia patients. Secondary Objectives * To describe whether an immune response, as measured by development of cell- and/or antibody-mediated influenza specific responses, is detectable 1-2 weeks following vaccination in a cohort of pediatric leukemia patients. * To describe the durability of immunogenicity by measuring cell - and antibody- mediated influenza specific responses at 6 months and 1 year following vaccination in a cohort of pediatric leukemia patients. Exploratory Objectives * To estimate the clinical effectiveness of influenza vaccine in this cohort by monitoring for the development of clinical diagnosis of influenza in the cohort of enrolled pediatric oncology patients. * To correlate results of immune cell frequency in blood, as measured by complete blood count with differential, with development of an immune response to IIV.

The purpose of this study is to evaluate the long-term safety and the clinical benefit of pelabresib in patients with hematological and/or solid tumor indications or advanced malignancies. Additionally, participants previously enrolled in studies with pelabresib who received placebo or participants who discontinued pelabresib (for any other reason than participating in this extension study), may be enrolled in this extension study to evaluate the survival and leukemia-free survival (for patients with hematological malignancies) or only the Survival Follow-up (for all the other patients).

The allogeneic TCR-enhanced Vδ2 T cell product is a novel genetically engineered cellular therapeutic. By engineering a specific BTN protein-binding moiety on its cell surface, this product harnesses the intrinsic tumoricidal potential of endogenous Vδ2 T cells and augments BTN protein recognition capability, thereby significantly boosting tumor cell killing potency. Notably, this engineered cell product exhibits no expression of co-stimulatory signaling domains and CD3ζ domains. This design circumvents T cell exhaustion triggered by overactivation and markedly enhances the in vivo persistence of therapeutic cells. This is an open, prospective, open-label Phase I/II clinical trial designed to assess the safety and therapeutic efficacy of allogeneic TCR-enhanced Vδ2 T cell injection in patients with relapsed or refractory hematologic malignancies and advanced solid tumors.