Clinical Research Directory

Autologous T Cells Transduced With Retroviral Vectors Expressing TCRs for Participant-specific Neoantigens in Patients With Hematologic Malignancies

Background: Blood cancers (such as leukemias) can be hard to treat, especially if they have mutations in the TP53 or RAS genes. These mutations can cause the cancer cells to create substances called neoepitopes. Researchers want to test a method of treating blood cancers by altering a person s T cells (a type of immune cell) to target neoepitopes. Objective: To test the use of neoepitope-specific T cells in people with blood cancers Eligibility: People aged 18 to 75 years with any of 9 blood cancers. Design: Participants will have a bone marrow biopsy: A sample of soft tissue will be removed from inside a pelvic bone. This is needed to confirm their diagnosis and the TP53 and RAS mutations in their cancer cells. They will also have a skin biopsy to look for these mutations in other tissue. Participants will undergo apheresis: Blood will be taken from their body through a vein. The blood will pass through a machine that separates out the T cells. The remaining blood will be returned to the body through a different vein. The T cells will be grown to become neoepitope-specific T cells. Participants receive drugs for 3 days to prepare their body for the treatment. The modified T cells will be given through a tube inserted into a vein. Participants will need to remain in the clinic at least 7 days after treatment. Participants will have 8 follow-up visits in the first year after treatment. They will have 6 more visits over the next 4 years. Long-term follow-up will go on for 10 more years.

Open-Label, Phase II Trial of Isatuximab for Patients With Refractory Immune Cytopenias After Allogeneic Hematopoietic Cell Transplantation

The purpose of this study is to find out whether isatuximab is an effective treatment for people who developed immune cytopenias/ICs after allogeneic hematopoietic cell transplant/allo-HCT.

A Multi-Site Break Through Cancer Trial: Targeting Measurable Residual Disease in Patients With Acute Myeloid Leukemia: A Phase 1/2 Study of Tagraxofusp, Azacitidine, and Venetoclax

The purpose of this research study is to test the safety and efficacy of a new drug combination with three agents, azacitidine, venetoclax and tagraxofusp. Leftover (residual) leukemia disease that is not visible by eye can be increase the chance of disease recurrence. This research study is to determine if the combination therapy can safely help to control residual Acute Myeloid Leukemia (AML) and to prevent disease recurrence. The names of the study drugs involved in this study are: * Tagraxofusp (a type of CD123-directed cytotoxin) * Azacitidine (a type of standard of care cytidine nucleoside analog) * Venetoclax (a type of standard of care BCL-2 inhibitor)

Development of a Multi-biomarker Panel for Prognostic Stratification and Treatment Response Prediction in Acute Graft Versus Host Disease of the Gut

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a life-saving treatment for many malignant hematologic diseases. Its curative potential is due to both high-dose chemotherapy and the graft-versus-host disease (GvHD) process, in which the donor's T cells recognize the recipient's tissue as foreign. However, GvHD is a potentially fatal complication that significantly affects both survival and quality of life. GvHD can be acute or chronic, and one of the main target organs involved in acute GvHD is the intestine, with a high rate of treatment failure and mortality. We expect to identify a set of biomarkers, both clinical and experimental, that will enable the stratification of patients based on prognosis and response to treatment in intestinal GvHD. The ultimate goal of the study is to integrate clinical, transplant, and biomarker data into a robust predictive algorithm. This tool will enable personalized therapeutic approaches based on early biomarkers, improving prognostic accuracy for patient outcomes and optimizing therapeutic strategies.

Immune Profiling for Cancer Immunotherapy Response

In patients clinically treated with FDA-approved immunotherapy the investigators will assess the predictive value of pre- and on-treatment 1) immune-methylation profiling across cancer types, and 2) immune-methylation profiling and cytokine profiling within cancer types.

Effect of APA on Sleep Quality in Children With Cancer From 5 to 16 Years

Main objective : Evaluate the effect of adapted physical activity on the sleep of children with cancer from 5 to 16 Hypothesis : Practice daily adapted physical activity improve the sleep of the 5 to 16 children with cancer

Pharmacogenomics for Better Treatment of Fungal Infections in Cancer

This project aims to address invasive fungal infections in patients with blood cancer, by precision dosing of voriconazole based on CYP2C19 genotype testing with Bayesian dose-forecasting dosing software to develop patient-centric and maximally effective dosing regimens. This study investigates if voriconazole increases the proportion of patients achieving therapeutic exposure at day 8 of dosing compared with standard care; and will assess factors that influence the implementation of genotype testing and dosing software in the healthcare system, including fidelity, feasibility, acceptability and cost-effectiveness. It will recruit at least 104 kids and adults in a parallel-group randomised clinical trial. A hybrid feasibility sub-study will assess the scalability of genotype-directed dosing to ensure sustainable integration of the interventions into the clinical workflow. A health economic sub-study will evaluate the costs, health outcomes and cost-effectiveness of genotype-directed testing compared to standard care.

A Music Therapy Study for Blood Cancer Survivors With Cognitive Difficulties

Research has shown that music-based activities may help improve brain functions, such as attention, memory, and executive function. Because of this past research, the researchers are doing this study to find out whether telehealth music therapy is a practical treatment for cognitive difficulties in blood cancer survivors. The researchers will also study whether music therapy and music education help improve cognitive function and other common symptoms such as anxiety, depression, and/or tiredness.

Take the Reins: The Effects of Nutrient Timing on Cancer-related Fatigue

Cancer-related fatigue affects at least 30-90% of patients with cancer, depending on the type of cancer and their treatment(s) (e.g., chemotherapy, radiation). It is not relieved by sleep or rest, and it sometimes can persist for years after a person's cancer was treated. The fatigue can be so bad that people cannot return to work, hobbies, family roles, or other daily activities, thereby greatly reducing quality of life. The causes of this fatigue are unknown, and we currently do not have anything that can reliably prevent or cure the fatigue. However, there are recent data suggesting that circadian rhythm, or a person's internal body clock, may be disrupted by the cancer experience and contribute to fatigue. Food intake is an external cue that can entrain circadian rhythm. We recently showed that cancer survivors are willing and able to eat all their food within a 10-hour eating window-a practice called time-restricted eating. Herein, we are testing time-restricted eating against a control group (matched for time-, attention, and expectancy) to see if time-restricted eating can indeed alleviate cancer-related fatigue. All participants will be asked to use the myCircadianClock smartphone app to log their food intake and weekly body weight measurements. The participants assigned to the time-restricted eating group will be asked to eat all their food in a 10-hour window during the day. People can choose their start time based on their schedule and preferences, but we ask that the window is the same for the whole study (e.g., 7am-5pm,9:30am-7:30pm). Black coffee and unsweetened tea are allowed before the eating window, and water and medicines are allowed at all times. The participants in the control group will meet with a nutritionist to discuss the American Cancer Society nutrition guidelines in cancer survivorship; they will not be restricted to when they can eat. Participants in both groups will give us valuable information regarding how diet is related to the experience of fatigue. The purpose of this study is to test the effects of a 12-week TRE intervention vs. an unrestricted eating pattern on fatigue, the sustainability of the program at 24 weeks, and the effects of TRE on circadian rhythm and sugar metabolism.

Driving Inclusivity, Validity, and Equity in Research Through Strategic Engagement (DIVERSE)

The purpose of this research study is to enhance inclusion and diversity in clinical trial enrollment by training participants to perform and provide feedback through a community-based protocol review process, called DIVERSE.

IDP-023 as a Single Agent and in Combination With Antibody Therapies in Patients With Advanced Hematologic Cancers

This is an open label, Phase 1/2, first-in-human, multiple ascending dose, and dose-expansion study of IDP-023 administered as a single agent and in combination with or without interleukin-2 (IL-2), and with or without isatuximab, daratumumab or rituximab to evaluate the safety, tolerability and preliminary antitumor activity in patients with advanced hematologic cancers.

Understanding the Implementation of Cued Exercise Using Wearable Devices and a Custom Smartphone Application Following Bone Marrow Transplant.

The purpose of this study is to pilot test the feasibility of providing patients diagnosed with a hematologic malignancy, undergoing an allogeneic bone marrow transplant, a wearable device and smartphone app (similar to a Fitbit), that would send personalized reminders to move during their post-transplant inpatient hospital stay to promote physical recovery and well-being.

Development of an Intervention Integrating Procedures Combining Hypnosis and Virtual Reality in the Support of Patients with Hematological Cancer

Research into cancer patients has shown that quality of life is significantly altered by the disease and its associated treatments and is also reported to be a predictor of significant emotional distress. Blood cancer patients are among those most affected in terms of quality of life, facing stem cell transplantation after high-dose chemotherapy, a treatment that is recognized as one of the most stressful of cancer therapy, due to the many adverse effects, including pain, and the uncertainty linked to the fear of graft failure. Hypnosis interventions are proving effective in treating common side effects: nausea, pain, fatigue, anxiety, depressive symptoms and improving overall quality of life, and other interventions, based on virtual reality, have shown promising effects on patients' distress and acute pain. The aim of this study is to evaluate the effects of an intervention program combining hypnosis and virtual reality in assisting myeloma and lymphoma patients during stem cell transplantation, with a view to improving their quality of life during this period. The project aims to assess the validity of the intervention, and to evaluate the effects of the intervention on patients' anxiety, pain and fatigue during transplantation. The validity of the intervention will be measured by a questionnaire assessing the relevance and acceptability of the intervention, expected effects, and practical implementation. Socio-demographic and clinical data will be collected from patients, including axiety, pain, fatigue and quality of life, studied at pre (one week after transplantation) and post (one month after transplantation) intervnention, and at follow-up (three month after transplantation).

Better Leukemia Diagnostics Through AI (BELUGA)

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.

Clinical Evaluation of the Scopio Cell Morphology Technology

Digital morphology is currently expanding and developing new applications based on artificial intelligence software. We recently published a study comparing screen validation and microscopic reading of bone marrow aspirates. The aim of the current research will be the comparison between optical microscope reading and automatic pre-classification (AI based)

Early Integration of Palliative and Supportive Care in Cellular Therapy

Research has shown that early palliative care in cancer care is associated with improved symptom management, better prognostic understanding, improved quality of life for patients and family caregivers, and even improved survival. Yet, in spite of the proven benefits of integration of palliative care in oncology, it has been well established that patients with hematologic malignancies and those undergoing cellular therapy (hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor (CAR) T-cell therapy) do not routinely receive palliative care. Most of the published research on the early integration of palliative care in oncology describes studies that have involved patients with solid tumours. To date, only one randomized trial examining the impact of integrated palliative care among patients undergoing HSCT has been published and there have been no studies examining the impact of integrated palliative care for patients undergoing CAR T-cell therapy. The American Society of Clinical Oncology recommends early palliative care for patients with advanced cancers or for those with high symptom burden. Patients with blood cancers experience high symptom burden and in the last 30 days of life, compared to patients with solid tumours, patients with blood cancers are more likely to die in hospital, have more intensive care unit admissions, have prolonged hospitalizations (\>14 days), and pass away in an acute care facility. There is an urgent need to proactively address suffering throughout cellular therapy trajectories, even before treatment starts, so that patients and caregivers are not inevitably waiting for symptoms to arise before they can be addressed and to optimize quality of life for patients undergoing transplant as well as their family caregivers. PALS\_CT will compare early palliative care to standard care for patients and their family caregivers undergoing HSCT or CAR T-cell therapy for blood cancers.

Defining the Role of Palliative carE for Patients With Hematologic Malignancies Undergoing Adoptive CEllular Therapy

The goal of this study is to determine whether a palliative care intervention (PEACE) can improve the quality of life and experiences of participants with Lymphoma, Leukemia, or Multiple Myeloma receiving adoptive cellular therapy (ACT). After completion of an open pilot, participants will be randomly assigned into one of two study intervention groups. The names of the study intervention groups involved in this study are: * Palliative care (PEACE) plus usual oncology care * Usual care (standard oncology care) Participation in this research study is expected to last for up to 2 years. It is expected that about 90 people will take part in this research study.

European Rare Blood Disorders Platform (ENROL)

ENROL, the European Rare Blood Disorders Platform has been conceived in the core of ERN-EuroBloodNet as an umbrella for both new and already existing registries on Rare Hematological Diseases (RHDs). ENROL aims at avoiding fragmentation of data by promoting the standards for patient registries' interoperability released by the EU RD platform. ENROL's principle is to maximize public benefit from data on RHDs opened up through the platform with the only restriction needed to guarantee patient rights and confidentiality, in agreement with EU regulations for cross-border sharing of personal data. Accordingly, ENROL will map the EU-level demographics, survival rates, diagnosis methods, genetic information, main clinical manifestations, and treatments in order to obtain epidemiological figures and identify trial cohorts for basic and clinical research. To this aim, ENROL will connect and facilitate the upgrading of existing RHD registries, while promoting the building of new ones when / where lacking. Target-driven actions will be carried out in collaboration with EURORDIS for educating patients and families about the benefits of enrolment in such registries, including different cultural and linguistic strategies. The standardized collection and monitoring of disease-specific healthcare outcomes through the ENROL user-friendly platform will determine how specialized care is delivered, where are the gaps in diagnosis, care, or treatment and where best to allocate financial, technical, or human resources. Moreover, it will allow for promoting research, especially for those issues that remain unanswered or sub-optimally addressed by the scientific community; furthermore, it will allow promoting clinical trials for new drugs. ENROL will enable the generation of evidence for better healthcare for RHD patients in the EU as the ultimate goal. ENROL officially started on 1st June 2020 with a duration of 36 months. ENROL is co-funded by the Health Programme of the European Union under the call for proposals HP-PJ-2019 on Rare disease registries for the European Reference Networks. GA number 947670

Allogeneic T Cells Expressing T Cell Receptor-KDEL and the Chimeric Antigen Receptor CAT19 for the Treatment of Advanced CD19+ Malignancies

KCAT19 is a single-centre, non-randomised, open-label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in adults (age 16-65 years) with high risk, relapsed/refractory (r/r) B cell malignancies.

The Leukemia and Lymphoma Society (LLS) National Research Registry

The Leukemia and Lymphoma Society (LLS) has built a National Research Registry to evaluate real world experiences and medical outcomes for people with blood cancer, before, during, and after blood cancer treatments.