Acute Lymphoblastic Leukemia

Background: B-cell acute lymphoblastic leukemia (B-ALL) is a type of blood cancer. Some people with B-ALL have a gene mutation that makes the disease hard to treat. The mutation causes cancer cells to make too much of a protein called thymic stromal lymphopoietin receptor (TSLPR). Chimeric antigen receptor (CAR) T cell therapy is a treatment that takes immune cells (T cells) from a person s body and modifies them to attack specific proteins. Researchers want to test whether TSLPR-CART cells can be given safely to adults with forms of B-cell leukemia, and to learn whether the treatment may help fight these cancers. Objective: To test TSLPR-CART in people with B-ALL. Eligibility: People aged 18 years and older with B-ALL that did not respond or returned after treatment. They must have TSLPR on their B-ALL. Design: Participants will be screened. They will have imaging scans and tests of their heart function. Samples will be taken from their bone marrow. They will have a lumbar puncture: A needle will be inserted into their back to collect a sample of the fluid around the spinal cord. Participants will undergo leukapheresis: Blood will be taken from their body through a tube. 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 tube. The T cells will be used to create TSLPR-CART. Participants will take chemotherapy over 5 days to prepare their body for the therapy; then they will receive the modified cells through a tube inserted into a vein. Staying in the hospital during part of the treatment is expected and participants will be monitored locally to evaluate for side effects. Approximately 1 month after receiving TSLPR-CART, participants will undergo evaluations to see how the TSLPR-CART impacted their leukemia. Participants will have follow-up visits for 2 years after TSLPR-CART either at NIH or at home....

Background: Chimeric antigen receptor T-cell (CART) therapy is a form of immunotherapy which can be used to treat people with relapsed B-ALL. For those who achieve remission after CART alone, it may cure up to 50% of people who receive this therapy. However, for people who relapse after CART, it can be hard to achieve remission again. In patients where CART fails, stem cell transplant (HCT) can be used to prevent relapse and achieve cure. But HCT can cause serious side effects. Better testing is needed to distinguish people who can be cured with CART alone from people who may also need to have HCT. Objective: To see if the use of a series of blood and bone marrow tests at regular intervals can help monitor for B-ALL relapse after CART therapy. Eligibility: People aged 1 to 25 years with B-ALL who have had CART therapy within the past 42 days. They must never have had a blood stem cell transplant; they must also have no measurable blood cancer cells. Design: Participants will visit the clinic every 2 weeks starting 42 days after they receive CART therapy. Each visit will be about the same amount of time as a regular clinic visit. about 8 hours. Participants will have blood drawn for testing on each visit. Bone marrow biopsy/aspirate will be done during 4 of the visits at routine timepoints after CART. A needle will be inserted to draw a sample of tissue from inside the bone in the hip. A small amount of blood and tissue will be tested with ClonoSEQ and to evaluate for normal B-cells side by side with the standard tests. The combined testing may help determine whether participants are eligible for HCT and/or at risk of relapse after CART. Participants will be in the study for 2 years.

Phase 1 dose escalation will determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of revumenib in participants with acute leukemia. In Phase 2, participants will be enrolled in 4 indication-specific expansion cohorts to determine the efficacy, short- and long-term safety, and tolerability of revumenib.

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and efficacy of ponatinib in children aged 1 to \< 18 years with advanced leukemias, lymphomas, and solid tumors.

This is a prospective data collection study evaluating the feasibility of using the ChromoSeq® assay for upfront classification in a real-time clinical setting of pediatric and young patients suspected of having ALL. Sixty patients will undergo collections of bone marrow and/or peripheral blood for the ChromoSeq® assay at time of initial workup as part of standard of care, and the patients will then be followed for clinical outcomes for up to 65 months.

This pilot study will evaluate the feasibility of implementing a structured digital patient-reported assessment pathway in adults aged 65 years or older with acute leukemia at Hospital Universitario Central de Asturias, Oviedo, Spain. Participants will complete the EORTC QLQ-C30 and FACT-Leu remotely after the baseline visit and repeat the digital assessment 8-12 weeks after individual activation of the MiAsturSalud/SESPA digital pathway. The primary outcome will be the proportion of participants answering at least 80% of the items in the baseline digital questionnaire battery within 7 days after the baseline visit. Secondary outcomes will be caregiver assistance requirement, non-completion of the planned digital follow-up assessment, and elapsed baseline questionnaire completion time. During this feasibility study, participants will not concurrently receive the broader project's home-monitoring and clinical-alert intervention. The questionnaire pathway will not generate automated clinical alerts. Usual clinical care will continue. The study is not designed to establish clinical efficacy.

This study collects blood and tissue samples from patients with cancer and without cancer to evaluate tests for early cancer detection. Collecting and storing samples of blood and tissue from patients with and without cancer to study in the laboratory may help researchers develop tests for the early detection of cancers.

The proposed research will compare the effects of TBI prior to CAR T cell infusion to the current standard of care using lymphodepletion.

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.

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. About 90% of children and young adults who are treated for ALL can now be cured. But if the disease comes back, the survival rate drops to less than 50%. Better treatments are needed for ALL relapses. Objective: To test chimeric antigen receptor (CAR) therapy. CARs are genetically modified cells created from each patient s own blood cells. his trial will use a new type of CAR T-cell that is targeting both CD19 and CD22 at the same time. CD19 and CD22 are proteins found on the surface of most types of ALL. Eligibility: People aged 3 to 39 with ALL or related B-cell lymphoma that has not been cured by standard therapy. Design: Participants will be screened. This will include: Physical exam Blood and urine tests Tests of their lung and heart function Imaging scans Bone marrow biopsy. A large needle will be inserted into the body to draw some tissues from the interior of a bone. Lumbar puncture. A needle will be inserted into the lower back to draw fluid from the area around the spinal cord. Participants will undergo apheresis. Their blood will circulate through a machine that separates blood into different parts. The portion containing T cells will be collected; the remaining cells and fluids will be returned to the body. The T cells will be changed in a laboratory to make them better at fighting cancer cells. Participants will receive chemotherapy starting 4 or 5 days before the CAR treatment. Participants will be admitted to the hospital. Their own modified T cells will be returned to their body. Participants will visit the clinic 2 times a week for 28 days after treatment. Follow-up will continue for 15 years....

This study will evaluate the safety, tolerability, and efficacy of engineered donor grafts ("OrcaGraft"/"Orca-Q") in participants undergoing allogeneic hematopoietic cell transplant (alloHCT) transplantation for hematologic malignancies.

Despite advances in cancer treatment, significant disparities in outcomes persist between high-income countries (HICs) and low-and middle-income countries (LMICs). Around 80% of children with cancer live in LMICs, where they face challenges such as delayed diagnosis, misdiagnosis, comorbidities, distance to treatment, financial barriers, and limited access to risk-adapted therapies. Acute lymphoblastic leukemia(ALL)/lymphoblastic lymphoma(LBL), for example, is one of the greatest success stories in pediatric oncology, however, such improvements are not evenly distributed worldwide, and the outcomes for leukemia patients are poorer in LMICs compared to HICs, primarily due to reduced access to quality healthcare. This study aims to assess cancer treatment outcomes in LMICs, focusing on acute lymphoblastic leukemia/lymphoblastic lymphoma. The findings will inform future studies to implement evidence-based interventions that improve care quality and reduce treatment failures through targeted strategies.

This is a Phase 2 Study is to determine the efficacy and safety rate of B-Cell Acute Lymphoblastic Leukemia (B-ALL) participants in remission with minimal residual disease (MRD) after KTE-X19 CAR T-cell therapy

This prospective, randomized, multicenter, open-label Phase 2 study is designed to evaluate the superiority of InO monotherapy vs ALLR3 after 1 cycle of induction treatment in paediatric participants (between 1 and \<18 years) with High Risk (HR) or very high risk (VHR) first bone marrow relapse CD22-positive BCP ALL, and to evaluate the safety and tolerability, PK and long-term efficacy. Treatment with study intervention will end after induction therapy; follow-up will continue for up to 5 years from randomization.

To learn if the combination of blinatumomab and asciminib can help to control Ph+ ALL.

This is a phase II clinical study to evaluate the safety and efficacy of pCAR-19 B cell autologous infusion preparation in the treatment of CD19-positive relapsed/refractory B-cell acute lymphoblastic leukemia.

Multi-center, open-label, single arm study of asciminib in participants aged ≥1 year to ≤30 years old with r/r Ph+ or ABL-class Ph-like ALL. This study will have 2 parts: Part 1 dose escalation and Part 2 dose expansion. Part 1 dose escalation will enroll participants aged ≥1 year to ≤30 years to determine the recommended phase 2 dose (RP2D) of asciminib when administered with low intensity chemotherapy. Part 2 dose expansion will enroll participants aged ≥1 year to ≤30 years to evaluate safety, tolerability, and efficacy of asciminib at the RP2D with the treatment regimen.

This phase II trial tests how well removing CD45RA positive naive T cells works to prevent graft versus host disease in older patients undergoing standard of care allogeneic hematopoietic stem cell transplantation for the treatment of acute leukemia or myelodysplastic syndrome (MDS). Allogeneic hematopoietic stem cell transplantation is when healthy cells are collected from a donor and infused into a patient to help the patient's bone marrow make more healthy cells and platelets and help destroy any remaining cancer cells. Giving chemotherapy and total-body irradiation before a stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. Sometimes the transplanted cells from a donor can attack the body's normal cells (called graft-versus-host disease). Removing the T cells from the donor cells before the transplant may stop this from happening. Giving CD45RA positive naive T cell depleted allogenic hematopoietic stem cell transplant may prevent graft versus host disease while treating acute leukemia or myelodysplastic syndrome in older adults.

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 goal of this quasiexperimental cohort controlled intervention study is to learn if aloe vera mouthwash works better than usual care in the prevention and treatment of oral mucositis. Researchers will compare aloe vera to usual care. Participants in the intervention group will rinse their mouths with aloe vera 4 x/day for 28 days of their treatment. They will also complete questionnaires about oral health and mucositis.

The primary purpose of this study is to determine safety, feasibility, and the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of CD22 Chimeric Antigen Receptor T-Cell Therapy (CART) cells when administered 28 to 42 days after an infusion of a commercial CAR called Tisagenlecleucel, to children and young adults with relapsed or refractory B-cell leukemia.

This study is designed as a prospective, single-arm, exploratory clinical trial based on lishatoclax, enrolling three independent cohorts of patients with Philadelphia chromosome-positive (Ph⁺) ALL, Philadelphia chromosome-negative (Ph-) ALL, and T-cell ALL (T-ALL). By investigating the combination of lishatoclax with established standard chemotherapy, targeted agents (e.g., tyrosine kinase inhibitors, TKIs), or immunotherapies, this study aims to further improve the remission rates across all ALL subtypes, and to develop a more effective and less toxic novel therapeutic strategy for ALL, thereby addressing the unmet clinical needs in current practice.

This is an open label, non-randomized, phase 1 study of anti-CD19 CAR-T cells against relapsed CD19 positive NHL, CLL and ALL based in a lymphodepletion regimen (fludarabine and cyclophosphamide) and using a CellReGen-based process for manufacturing CAR-T cells. This study will utilize a staggered enrollment design with a safety observation period.

This study aims to use clinical and biological characteristics of acute leukemias to screen for patient eligibility for available pediatric leukemia sub-trials. Testing bone marrow and blood from patients with leukemia that has come back after treatment or is difficult to treat may provide information about the patient's leukemia that is important when deciding how to best treat it, and may help doctors find better ways to diagnose and treat leukemia in children, adolescents, and young adults.

The researchers are doing this study to find out whether obecabtagene autoleucel (obe-cel) is an effective treatment for people with B-cell acute lymphoblastic leukemia (ALL) that is in complete remission (CR, meaning all signs of cancer are gone) with no measurable residual disease (MRD-negative, meaning there are no detectable cancer cells). Participants in this study will have received past treatment for their B-cell ALL, and their disease will be in MRD-negative CR for the first time (first MRD-negative CR).