Dasatinib

The purpose of this study is to find out whether the combination of mezigdomide and revumenib is a safe treatment for people with relapsed or refractory KMT2A-r, NUP98-r, and NPM1-m acute leukemias.

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.

To find out if giving blinatumomab as injections under the skin can help to control MRD and keep the disease from coming back in participants with B-cell ALL.

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 pilot study aims to gather preliminary evidence on how different hemoglobin levels impact blood biomarkers related to bleeding. The feasibility of conducting a future larger clinical trial will also be assessed. Red blood cell transfusions are part of the standard of care for patients with leukemia. This study evaluates two transfusion strategies: one that maintains hemoglobin levels above the standard-of-care threshold, reflecting current routine practice; and another that maintains hemoglobin levels above 110 g/L, which is closer to the normal hemoglobin range. The normal hemoglobin range is 120-160 g/L for females and 140-180 g/L for males. Raising hemoglobin levels closer to normal values may reduce bleeding risk.

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.