Clinical Research Directory

Ruxolitinib With Tacrolimus and Methotrexate for the Prevention of Graft Versus Host Disease in Pediatric and Young Adult Patients Undergoing Allogeneic Hematopoietic Cell Transplant for Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

This phase II trial tests how well ruxolitinib with tacrolimus and methotrexate work to prevent the development of graft versus host disease in pediatric and young adult patients undergoing allogeneic hematopoietic cell transplant for acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome. Ruxolitinib is a type of medication called a kinase inhibitor. It works by blocking the signals of cells that cause inflammation and cell proliferation, which may help prevent graft versus host disease (GVHD). Tacrolimus is a drug used to help reduce the risk of rejection by the body of organ and bone marrow transplants by suppressing the immune system. Methotrexate stops cells from making DNA, may kill cancer cells, and also suppress the immune system, which may reduce the risk of GVHD. Giving ruxolitinib with tacrolimus and methotrexate may prevent GVHD in pediatric and young adults undergoing allogeneic hematopoietic cell transplants.

Intrathecal Chemoprophylaxis to Prevent Neurotoxicity Associated With Blinatumomab Therapy for Acute Lymphoblastic Leukemia

Changing the schedule of intrathecal chemotherapy to be given before and during blinatumomab will maintain the anti-leukemic effects of this drug while at the same time adding the benefit of limiting the neurotoxicity associated with cytokine release.

Adding Itacitinib to Cyclophosphamide and Tacrolimus for the Prevention of Graft Versus Host Disease in Patients Undergoing Hematopoietic Stem Cell Transplants

This clinical trial evaluates the safety and effectiveness of adding itacitinib to cyclophosphamide and tacrolimus for the prevention of graft versus host disease (GVHD) in patients undergoing hematopoietic stem cell transplant. Itacitinib is an enzyme inhibitor that may regulate the development, proliferation, and activation of immune cells important for GVHD development. Cyclophosphamide and tacrolimus are immunosuppressive agents that may prevent GVHD in patients who receive stem cell transplants. Giving itacitinib in addition to cyclophosphamide and tacrolimus may be more effective at preventing GVHD in patients receiving hematopoietic stem cell transplants.

Phase I Study of FXS0683 in the Treatment of Blood Tumors

This is a first-in-human, multicenter, open-label, single-arm Phase I study of FXS0683 in participants with relapsed or refractory hematologic malignancies to evaluate safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity, and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D).

A Multicenter Study to Evaluate Next-Generation Sequencing (NGS) Testing and Monitoring of B-Cell Recovery to Guide Management Following Chimeric Antigen Receptor T-cell (CART) Induced Remission in Children and Young Adults With B Lineage Acute Lymph...

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.

Anti-CRLF2-R/TSLPR Chimeric Antigen Receptor T Cells (TSLPR-CART) in Participants With Recurrent or Refractory CRLF2-R/TSLPR-Overexpressing B-Cell Acute Lymphoblastic Leukemia (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.

Leukapheresis for CAR or Adoptive Cell Therapy Manufacturing

Background: Leukapheresis is a procedure to separate and collect white blood cells. It is the first step in a treatment called CAR (chimeric antigen receptor) T-cell therapy. CAR-T therapy may be offered to people when their cancer comes back. The collected T-cells are used to make a special version of T-cells called CARs. Researchers want to collect these cells from people who may become eligible for a CAR T-cell study in the future. Objective: To identify people who have a high likelihood to benefit from CAR T-cell therapy early in their disease course and collect and store a T-cell product. Eligibility: People ages 3-65 with a form of leukemia or lymphoma that has not been cured by standard therapy Design: Participants will be screened with medical history, physical exam, and blood and urine tests. Review of existing MRI, x-ray, pathology specimens/reports or CT images may be done. On this study, participants will have leukapheresis. A needle will be placed into the arm. Blood will be collected and go through a machine. White blood cells will be taken out by the machine. The plasma and red cells will be returned to the participant through a second needle in the other arm. The procedure will take 4-6 hours. Some participants may have a central line (catheter) inserted which is needed to do the leukapheresis procedure, instead of the needles in the arms-especially if they are smaller. For a central line placement, a long thin tube is inserted through a small incision into the main blood vessel leading into the heart that would allow access to the blood to do the leukapheresis procedure. Participants cells will be processed and frozen for future use in a CAR T-cell therapy study. ...

Phase I/II Study of the Combination of Blinatumomab and Asciminib in Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

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

A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation

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.

Whole Genome Sequencing (ChromoSeq®) for Acute Lymphoblastic Leukemia (ALL) Patients

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.

Safety and Efficacy of Ponatinib for Treatment of Pediatric Recurrent or Refractory Leukemias, Lymphomas or Solid Tumors

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.

Phase 2 Study to Assess the Safety and Efficacy of Subcutaneous Blinatumomab in Patients With Measurable Residual Disease Positive B-cell Acute Lymphoblastic Leukemia

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.

Digital Patient-Reported Assessment in Older Adults With Acute Leukemia

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.

Effects of Core Stabilization Exercises in Children With Acute Lymphoblastic Leukemia

The goal of this clinical trial is to investigate the effects of core stabilization exercises applied in addition to the conventional exercise program on physical function, functional muscle strength, functional exercise capacity, postural control and fatigue in children with acute lymphoblastic leukemia receiving maintenance treatment. Participants will be divided into two groups; the first group will be given a conventional exercise program, while the second group will be given core stabilization exercises in addition to the conventional exercise program.

Combination Chemotherapy and Ponatinib Hydrochloride in Treating Patients With Acute Lymphoblastic Leukemia

This phase II trial studies the side effects and how well combination chemotherapy and ponatinib hydrochloride work in treating patients with acute lymphoblastic leukemia. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ponatinib hydrochloride may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy and ponatinib hydrochloride may be an effective treatment for acute lymphoblastic leukemia.

A Study of Different Programs to Help ALL Patients With Taking Maintenance Medicine at Home

This clinical trial tests different programs to help patients with acute lymphoblastic leukemia (ALL) remember to take their medications during maintenance therapy at home. One problem with ALL maintenance treatment is remembering to take medicines at home like patients are supposed to. In maintenance, a medicine called 6-mercaptopurine or "6MP" is taken by mouth every day at home. In this study, 6MP prescriptions are filled into a special medication bottle called MEMS® which is fitted with a special cap called TrackCap™ that electronically records when the medication bottle is opened. Researchers are trying a new program to help patients be better at taking their 6MP like they're supposed to. This new program may help patients to remember to take their 6MP medication.

2 Gy Total Body Irradiation As Part Of Conditioning Treatment For Patients With Acute Lymphoblastic Leukemia Undergoing CAR T Cell Therapy

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

Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

This randomized phase III trial studies how well imatinib mesylate works in combination with two different chemotherapy regimens in treating patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (ALL). Imatinib mesylate has been shown to improve outcomes in children and adolescents with Philadelphia chromosome positive (Ph+) ALL when given with strong chemotherapy, but the combination has many side effects. This trial is testing whether a different chemotherapy regimen may work as well as the stronger one but have fewer side effects when given with imatinib. The trial is also testing how well the combination of chemotherapy and imatinib works in another group of patients with a type of ALL that is similar to Ph+ ALL. This type of ALL is called "ABL-class fusion positive ALL", and because it is similar to Ph+ ALL, is thought it will respond well to the combination of agents used to treat Ph+ ALL.

Administration of Donor T Cells With the Caspase-9 Suicide Gene

Patients will be receiving a stem cell transplant as treatment for their disease. As part of the stem cell transplant, patients will be given very strong doses of chemotherapy, which will kill all their existing stem cells. A close relative of the patient will be identified, whose stem cells are not a perfect match for the patient's, but can be used. This type of transplant is called "allogeneic", meaning that the cells are from a donor. With this type of donor who is not a perfect match, there is typically an increased risk of developing GvHD, and a longer delay in the recovery of the immune system. GvHD is a serious and sometimes fatal side-effect of stem cell transplant. GvHD occurs when the new donor cells (graft) recognize that the body tissues of the patient (host) are different from those of the donor. In this study, investigators are trying to see whether they can make special T cells in the laboratory that can be given to the patient to help their immune system recover faster. As a safety measure, we want to "program" the T cells so that if, after they have been given to the patient, they start to cause GvHD, we can destroy them ("suicide gene"). Investigators will obtain T cells from a donor, culture them in the laboratory, and then introduce the "suicide gene" which makes the cells sensitive to a specific drug called AP1903. If the specially modified T cells begin to cause GvHD, the investigators can kill the cells by administering AP1903 to the patient. We have had encouraging results in a previous study regarding the effective elimination of T cells causing GvHD, while sparing a sufficient number of T cells to fight infection and potentially cancer. More specifically, T cells made to carry a gene called iCasp9 can be killed when they encounter the drug AP1903. To get the iCasp9 gene into T cells, we insert it using a virus called a retrovirus that has been made for this study. The AP1903 that will be used to "activate" the iCasp9 is an experimental drug that has been tested in a study in normal donors with no bad side-effects. We hope we can use this drug to kill the T cells. The major purpose of this study is to find a safe and effective dose of "iCasp9" T cells that can be given to patients who receive an allogeneic stem cell transplant. Another important purpose of this study is to find out whether these special T cells can help the patient's immune system recover faster after the transplant than they would have otherwise.

Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection

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.

Levofloxacin Prophylaxis to Prevent First Febrile Neutropenia in Pediatric ALL During Induction Phase

The goal of this clinical trial is To evaluate the benefit of levofloxacin prophylaxis in prolonging the median time to first febrile neutropenia in pediatric ALL patients during induction phase. It will also learn about the safety of levofloxacin during induction treatment. The main questions it aims to answer are: * Does levofloxacin prophylaxis increase the median time to the first febrile neutropenia episode compared to placebo? * What are the rates of fever, severe infection, organ-related bacterial infection, and mortality in children receiving levofloxacin compared to placebo? Researchers will compare oral levofloxacin to a placebo (a look-alike substance with no active drug) to see if levofloxacin is effective in preventing infection during induction chemotherapy. Participants will: * Be children aged 1 to 18 years with ALL undergoing induction chemotherapy. * Be randomly assigned to receive either levofloxacin prophylaxis or placebo during the induction phase. * Have regular checkups, physical exams, and laboratory tests during induction. * Be monitored for fever, febrile neutropenia, severe infections, bacterial infections, and mortality. * Stop prophylaxis once the first febrile neutropenia occurs or induction therapy is completed.

CD22 CAR T-cells to Extend Remission Following Commercial CD19 CAR T-cells in Children, Adolescents, and Adults With Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia

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.

CD19/CD22 Bicistronic Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory B Cell Malignancies

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....

Pilot Prospective Study for PET-CT Imaging in Participants With Relapsed/Refractory Acute Leukemias

Background Acute lymphoblastic leukemia (ALL) accounts for about 25 percent of childhood cancers and for about 20 percent of adult leukemias. The disease can be treated with CAR T-cell infusion but non-central nervous system (CNS) extramedullary disease (EMD) is associated with lower rates of complete remission. 18-fludeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) has been shown to be effective for detection of non-CNS EMD in ALL. Pre and post CAR T-cell infusion may help to predict outcomes and risk of early progression. Objectives To describe the number of adults with relapsed/refractory B-cell ALL who proceed to CAR T-cell therapy. Eligibility Participants \>=18 years with relapsed/refractory B-cell ALL who are being screened for CAR T-cell clinical trial enrollment, and Participants \<18 with relapsed/refractory B cell ALL who are being screened for CAR T-cell clinical trial enrollment and have a clinical indication for FDG PET-CT prior to CAR infusion. Design Pilot study to add screening FDG PET-CT as part of the pre-CAR T-cell baseline evaluation with additional imaging at day 28 and future timepoints pending evidence of non-CNS EMD on initial scan.