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.

Researchers are looking for new ways to treat people with a type of blood cancer called precursor B-cell Acute Lymphoblastic Leukemia (B-ALL) that is relapsed- the cancer has come back after treatment, or refractory - the current treatment has stopped working to slow or stop cancer growth. This study will have two parts. In the first part (dose escalation phase) the goal is to learn about the safety of a study treatment, MK-1045, and to find the best dose level of MK-1045 that is tolerated and may work to treat B-ALL. In the second part (Phase II) researchers want to learn how well MK-1045 works to treat B-ALL.

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....

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.

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.

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.

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.

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.

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 is a small-scale micro-randomized clinical trial of a new mobile just-in-time adaptive intervention (JITAI) designed to promote oral chemotherapy adherence in adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL). The goals of this study are to determine intervention feasibility and acceptability.

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.

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).

This phase II trial studies how well vedolizumab plus post-transplant cyclophosphamide (PTCy) and short course tacrolimus work for the prevention of graft versus host disease (GVHD) in patients undergoing allogeneic hematopoietic cell transplantation (HCT) after reduced intensity conditioning. Allogeneic HCT is a procedure in which a person receives blood-forming stem cells (cells from which all blood cells develop) from a donor. Giving reduced conditioning chemotherapy before an allogeneic HCT helps kill cancer cells in the body and helps make room in the patient's bone marrow for new stem cells to grow using less than standard doses of chemotherapy. Sometimes, the transplanted cells from a donor can attack the body's normal cells (called graft-versus-host disease). Vedolizumab is a monoclonal antibody, which is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). It may reduce inflammation. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid and may kill cancer cells. It may also lower the body's immune response. Tacrolimus suppresses the immune system by preventing the activation of certain types of immune cells. Giving vedolizumab plus PTCy and short course tacrolimus may be effective at preventing GVHD after allogeneic HCT.

This study will test if adding ruxolitinib to standard multi-drug chemotherapy regimen will be safe and tolerated in adolescents and young adults with newly diagnosed Ph-like acute lymphoblastic leukemia (ALL).

Background: Chronic lymphocytic leukemia (CLL),small lymphocytic lymphoma (SLL) and B-cell acute lymphoblastic leukemia or lymphoma (ALL) are blood cancers that affect certain white blood cells. Advanced forms of these diseases are difficult to treat. CD19 is a protein often found on the surfaces of these cancer cells. Researchers can modify a person's own immune cells (T cells) to target CD19. When these modified T cells are returned to the body-a treatment called anti-CD19 chimeric antigen receptor (CAR) T cell therapy-they may help kill cancer cells. Objective: To test anti-CD19 CAR T cell therapy in people with CLL or SLL and ALL. Eligibility: People aged 18 years and older with CLL or SLL and ALL that has not been controlled with standard drugs. Design: Participants will be screened. They will have imaging scans and tests of their heart function. If a sample of tissue from their tumor is not available, a new one may be taken; the sample will be tested for CD19. Participants will receive a drug to reduce the leukemia cells in their blood. Then they will undergo apheresis: Blood will be taken from the body through a needle. 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 needle. The collected T cells will be gene edited to make them attack cells with CD19. Participants will take drugs to prepare them for treatment for 3 days. These drugs will start 5 days before the treatment. Then their own modified CAR T cells will be returned to their bloodstream. Participants will stay in the hospital for at least 9 days after the treatment. Follow-up visits will continue for 5 years.

This is a Phase II study of allogeneic hematopoietic stem cell transplant (HCT) using a myeloablative preparative regimen (of either total body irradiation (TBI); or, fludarabine/busulfan for patients unable to receive further radiation). followed by a post-transplant graft-versus-host disease (GVHD) prophylaxis regimen of post-transplant cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF).

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.

This phase I/II trial studies the side effects and best dose of 211\^astatine(At)-BC8-B10 before donor stem cell transplant in treating patients with high-risk acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or mixed-phenotype acute leukemia. Radioactive substances, such as astatine-211, linked to monoclonal antibodies, such as BC8, can bind to cancer cells and give off radiation which may help kill cancer cells and have less of an effect on healthy cells before donor stem cell transplant.

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 purpose of this section is to learn how text message reminders might help with regularly taking chemotherapy medications for Adolescents and Adults with Acute Lymphoblastic leukemia (ALL).

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.

This study was designed as a prospective, multicenter, open-label, randomized controlled trial. Eligible participants were patients aged 15-65 years with high risk or relapsed/refractory acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic neoplasms (MDS), diagnosed based on bone marrow morphology, immunophenotyping, genetic testing, and treatment response assessment. The experimental group received SHR2554 combined with azacitidine as an overlapped sequential combination with the mBuCy conditioning regimen, whereas the control group received the mBuCy conditioning regimen, both followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). The primary endpoint is 1-year event-free survival (EFS). Secondary endpoints include 2-year overall survival, 2-year cumulative incidence of relapse, transplant-related mortality, incidence of acute/chronic GVHD, and safety profiles.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children and, along with lymphoblastic lymphoma, represents the most common group of childhood lymphoid malignancies. Survival rates have improved over the years, but many children still experience long-term side effects from treatment. These can include tiredness, weak muscles, pain, nerve problems, difficulty moving, and other physical challenges. Many children with ALL are also overweight at diagnosis, and weight gain often continues during treatment. As a result, about half of childhood leukemia survivors have a BMI at or above the 85th percentile. Treatment decisions are usually based on a child's symptoms and genetic risk factors. However, some risk factors such as physical activity can be modified. Exercise during treatment may help children feel better and may even improve survival. However, research on early symptom tracking and structured exercise during the first phase of chemotherapy is limited, uses different methods, and often does not include reliable patient-reported symptoms. Effective exercise programs for children with ALL and lymphoblastic lymphoma need to consider the child's age, treatment side effects, motivation, family support, and ways to encourage long-term behavior change. Because children spend little time in the hospital during the induction phase, a mix of in-person and virtual sessions supported by real-time Zoom instruction can make it possible to offer safe and supervised exercise at home. This study will use a guided exercise plan that includes tools to track sets, repetitions, intensity, warm-up time, and perceived exertion. These tools help with consistent monitoring and support both patients and caregivers throughout the program. Twenty children newly diagnosed with ALL or lymphoblastic lymphoma who receive standard 3-4 drug induction chemotherapy will be invited to participate. Our goal is to determine whether a 9-week hybrid exercise program, combined with weekly symptom check-ins, is practical and achievable in both hospital and home settings.