Sprycel

Background: Acute lymphoblastic leukemia (ALL) is a type of blood cancer. Chimeric antigen receptor (CAR) therapy involves taking immune cells (T cells) from a person and modifying them to better target cancer cells. CAR T-cell therapy that targets a marker called CD19 has been show to can cure ALL in many children and adults. But in about 50% of patients, the ALL comes back within a year. Researchers want to find out if a second treatment with CAR T-cell therapy that targets a different marker, CD22, can keep the cancer away longer. Objective: To see if CD22 CAR T-cell therapy can keep ALL away longer. Eligibility: People aged 3 to 65 years who have no signs of cancer after CD19 CAR T-cell treatment for ALL. Design: Participants will be screened. They will have imaging scans and tests of their heart function. A sample of tissue (biopsy) will be collected from their bone marrow. They will have a fluid sample collected from the area around their spinal cord. Participants will undergo collection of their white blood cells (T cells) during a procedure called leukapheresis. 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 cells will be altered in a lab to create CD22 CAR T-cell therapy. Participants will take drugs over 4 consecutive days to prepare their body for the CAR T-cell therapy; then they will receive their modified T cells through a tube inserted into a vein. Some people may need to stay in the hospital during treatment. Participants will have follow-up visits for 2 years.

The primary objective of this proposal is to conduct the first-in-human randomized clinical trial evaluating prophylactic DLI-X (pro-DLI-X) for relapse prevention following matched sibling donor (MSD) or haploidentical (haplo) hematopoietic cell transplantation (HCT) in patients with hematologic malignancies. Additionally, the study aims to assess the safety and efficacy of therapeutic DLI-X (t-DLI-X) compared to t-DLI alone in patients with minimal residual disease (MRD+) or overt relapse post-alloHCT. For patients with CD19-positive lymphoid malignancies, the study will incorporate blinatumomab, while those with myeloid or CD19-negative lymphoid malignancies will receive t-DLI-X or t-DLI alone. We hypothesize that both pro-DLI-X and t-DLI-X, with or without blinatumomab, will demonstrate safety and superior efficacy by enhancing graft-versus-leukemia (GvL) effects mediated by natural killer (NK) cells, γδ T cells, and CD8+ T cells, while maintaining manageable and treatment-responsive graft-versus-host disease (GvHD).

This is a 28-week, single-arm, open-label phase II clinical trial evaluating the combination of Tirzepatide and remote, supervised, tailored resistance exercise training to achieve weight loss in adult survivors of childhood acute lymphoblastic leukemia (ALL) living with obesity or overweight with comorbidity. Primary Objective(s): • To evaluate the effectiveness for weight loss of the combined intervention using once weekly Tirzepatide plus remote, supervised, tailored resistance exercise (three sessions per week) in adult survivors of childhood ALL with obesity or overweight (BMI ≥27 kg/m2) with ≥1 weight-related comorbidity (hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease). The effectiveness will be estimated as the proportion of evaluable participants who achieve at least 5% weight loss from baseline to week 28. The study will target a proportion of participants achieving 5% weight loss of 70% and consider fewer than 40% achieving 5% weight loss as unacceptable. Secondary Objective(s): * Estimate the proportion of participants who adhere to the 28-week combined intervention. Adherence to Tirzepatide will be defined as receiving at least 70% of prescribed doses. Adherence to resistance exercise will be defined as attending at least 50% of prescribed exercise sessions. Adherence to the combined intervention will be considered if participants complete the study and meet both the Tirzepatide and exercise adherence endpoint. The adherence to each component of the intervention will also be reported. * Estimate the average percentage weight loss from week 0 to 28 for participants completing the combined 28-week intervention. The study will target a mean weight reduction of 10% and consider \<5% unacceptable.

The goal of this study is to determine whether a mobile application that combines real-time sensor data and patient-reported symptoms to trigger care-team contact recommendations is feasible and beneficial for patients receiving chemotherapy. The main questions it aims to answer are: * Is the mobile application feasible and acceptable to patients? * Do the alerts and guidance improve symptom management, quality of life, and engagement with the care team during treatment? Participants will: * Complete a demographic questionnaire at the beginning of the study and quality-of-life and health questionnaires at the beginning, midpoint, and end of study. * Complete daily symptom ratings via study application. * Wear a Fitbit activity tracker for 90 days. * At the end of the study, complete a semi-structured interview to provide feedback on the study. * Optional: At the beginning and end of the study, complete an in-person physical function assessment measuring balance (Short Physical Performance Battery).

The study purpose is to gain a better understanding of the needs of adults aged 65 and older while they are receiving chemotherapy by measuring their resilience and tailor care plans based on their individual needs.

The purpose of this study is to understand the safety, tolerability, efficacy, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary efficacy of orally administered AZD3632 in participants with advanced haematologic malignancies with KMT2Ar, NPM1m, or other genotypes associated with homeobox (HOX) overexpression.

The goal of this clinical research study is to learn if obecabtagene autoleucel (obe-cel) can help to control newly diagnosed, high-risk B-cell ALL when given as consolidation therapy. Consolidation therapy is given after the first phase of treatment.

This phase Ib trial tests the safety, side effects, and how well cytomegalovirus (CMV)-modified vaccinia Ankara (MVA) Triplex vaccine works in enhancing CMV-specific immunity and preventing CMV viremia in patients undergoing haploidentical hematopoietic stem cell transplant. Haploidentical stem cell transplantation (haploHCT) has advanced to become the predominant procedure for patients lacking a matched donor. Compared to matched related donor transplants, the rate of significant CMV infection is higher in patients undergoing a haploHCT. Significant CMV infection is associated with an increased risk of complications and death. Vaccination is the main preventative approach to limit complications and death in immunocompromised patients at high risk of post-stem cell transplant infections. CMV-MVA Triplex vaccine, is a CMV vaccine based on the attenuated poxvirus, modified vaccinia Ankara (MVA), developed to enhance CMV-specific immunity in both healthy stem cell transplant donors and stem cell transplant patients to prevent significant CMV infection post-stem cell transplant. Giving CMV-MVA triplex vaccine may be safe, tolerable and/or effective in enhancing cytomegalovirus (CMV)-specific immunity and preventing CMV viremia in patients undergoing a haploHCT.

The purpose of this study is to see if see if adding the specific combination of donors can result in acceptable levels of survival without evidence of disease.

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.

The purpose of this clinical trial is to compare drug combinations to learn which drugs work best to prevent graft-versus-host-disease (GVHD) in people who have received a stem cell transplant. The source of stem cells is from someone who is not related and has a different blood cell type than the study participant. The researchers will compare the new drug combination to a standard drug combination. They will also learn about the safety of each drug combination. Participants will: * Receive the standard or new drug combination after transplant * Visit the doctor's office for check-ups and tests after transplant that are routine for most transplant patients * Take surveys about physical and emotional well-being * Give blood and stool samples.

CAR19PK is a research study evaluating the use of lymphodepleting chemotherapy and chimeric antigen receptor (CAR) T cell therapy, a type of cellular therapy, for the treatment of refractory and/or relapsed leukemia. For this type of therapy, peripheral (circulating) immune cells are collected and then modified so that they can recognize an antigen, which is a particle present on the surface of a cancer cell. The CD19-CAR T cell product will be manufactured at the St. Jude Children's Research Hospital's Good Manufacturing Practice (GMP) facility. The main purpose of this study is to determine: * Evaluate different doses of fludarabine prior CAR T cell infusion * How your body processes fludarabine and cyclophosphamide, * How long the CAR T cells last in the body, * Whether or not treatment with this therapy is effective in treating people with refractory or relapsed leukemia, and * The side effects of this therapy.