Clinical Research Directory

Blinatumomab and Combination Chemotherapy or Dasatinib, Prednisone, and Blinatumomab in Treating Older Patients With Acute Lymphoblastic Leukemia

This phase II trial studies the side effects and how well blinatumomab and combination chemotherapy or dasatinib, prednisone, and blinatumomab work in treating older patients with acute lymphoblastic leukemia. Immunotherapy with monoclonal antibodies, such as blinatumomab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as prednisone, vincristine sulfate, methotrexate, and mercaptopurine, 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. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving blinatumomab with combination chemotherapy or dasatinib and prednisone may kill more cancer cells.

A 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 Lymphoblastic Leu...

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.

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.

Combination Chemotherapy With or Without Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia

This phase II trial is studying the side effects of giving combination chemotherapy together with or without donor stem cell transplant and to see how well it works in treating patients with acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Giving chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect).

The Pediatric Acute Leukemia (PedAL) Screening Trial - A Study to Test Bone Marrow and Blood in Children With Leukemia That Has Come Back After Treatment or Is Difficult to Treat - A Leukemia & Lymphoma Society and Children's Oncology Group Study

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.

Backtracking Leukemia-Typical Somatic Mutations in Cord Blood

A comprehensive mechanistic and epidemiological study to obtain banked cord blood samples from consecutive childhood leukemia patients enrolled in the COG Project:EveryChild (APEC14B1) study. Will attempt to backtrack the initiating genomic alteration identified in the matched diagnostic leukemia sample and molecularly characterize pre-leukemic cells. The ultimate goal of this research is to pinpoint the cell of origin of leukemogenic alterations formed in utero, elucidating the etiology of these initiating mutations (as opposed to frank leukemia), and devising a test for circulating pre-leukemia that can be applied on a population-wide basis.

The Association Between Gut Microbiome Composition Signature and Cancer-related Symptoms in Children With Acute Lymphoblastic Leukemia

This study is a prospective longitudinal investigation. Data on disease-related information, gut microbiota composition, cancer-related symptoms, dietary intake, and levels of pro-inflammatory cytokines, LPS were collected repeatedly at the following time points: before chemotherapy initiation, at the end of induction chemotherapy or Re-induction I, at 8 weeks after induction or re-induction therapy, at three months after induction or re-induction therapy, as well as weekly between chemotherapy initiation and the end of induction chemotherapy or Re-induction I. The aim is to explore the relationship between gut microbiota composition and cancer-related symptoms.

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.

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.

Blinatumomab and Tyrosine Kinase Inhibitor Therapy in People With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

The purpose of this study is to test whether blinatumomab in combination with TKI therapy (such as dasatinib) is an effective treatment for people with Ph+ ALL. Researchers want to improve the response to standard-of-care treatment of corticosteroids + TKI therapy by adding the study drug, blinatumomab.

Childhood Cancer Survivors' Affective Response to Exercise

The primary objective of this study is to assess the feasibility of administering the Personalized Single-Category Implicit Association Test (PSC-IAT) to young adult survivors of childhood cancer. Participants will perform a total of three trials of a cognitive task before and after their scheduled SJLIFE cardiovascular stress testing. Participants will then be asked to participate in a qualitative interview about the cognitive task tool and body sensations and emotions experienced during exercise.

MT2021-08T Cell Receptor Alpha/Beta Depletion PBSC Transplantation for Heme Malignancies

This is a phase II, open-label, prospective study of T cell receptor alpha/beta depletion (TCR α/β TCD) peripheral blood stem cell (PBSC) transplantation for children and adults with hematological malignancies. This is a safety/feasibility study of the investigational procedure/product.

Phase I/II Study of Rapcabtagene Autoleucel in CLL, 3L+ DLBCL, r/r ALL and 1L HR LBCL

This is a phase I/II study to evaluate the feasibility, safety and preliminary antitumor efficacy of rapcabtagene autoleucel (also known as YTB323). Rapcabtagene autoleucel will be investigated in combination with ibrutinib in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and as single agent in diffuse large B-cell lymphoma (3L+ DLBCL), adult acute lymphoblastic leukemia (ALL) and 1st Line High Risk Large B-Cell Lymphoma (1L HR LBCL).

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.

Study of KTE-X19 in Minimal Residual Disease (MRD) Positive B-Cell Acute Lymphoblastic Leukemia (B-ALL)

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

Risk-Adapted Chemotherapy in Treating Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia or Localized B-Lineage Lymphoblastic Lymphoma

This partially randomized phase III trial studies the side effects of different combinations of risk-adapted chemotherapy regimens and how well they work in treating younger patients with newly diagnosed standard-risk acute lymphoblastic leukemia or B-lineage lymphoblastic lymphoma that is found only in the tissue or organ where it began (localized). Drugs used in chemotherapy 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. Giving more than one drug (combination chemotherapy), giving the drugs in different doses, and giving the drugs in different combinations may kill more cancer cells.

ESTABLISHMENT OF A PHARMACOKINETIC MODEL FOR ERWINASE PHARMACOKINETICS

The aim of this sub study is to optimize target trough attainment while minimizing high exposures that impose increased risk of side effects such as hyperammonemia. Clinical pharmacology is based on the principle that plasma drug concentrations are linked to therapeutic effects. Therefore, understanding plasma drug concentrations is critical to balancing efficacy and toxicity in oncology treatment (figure 2), as shown with Erwinase where elevated activity increases the risk of hyperammonemia. TDM can guide dose adjustments to reduce PK variability and improve outcomes. However, harnessing all information from TDM data can be challenging due to sparse and uneven sampling, and multiple sources of PK variability. Advanced analytical tools, such as pharmacometrics and population PK modelling, can address these complexities by quantifying exposure variability in patients and linking it to dosage, patient characteristics, and biomarkers. Methods: This is a NOPHO study. Within the NOPHO, Erwinase was administered intramuscularly (IM) at a dose of 20,000 IU/m² on a Mon-Wed-Fri schedule for two weeks. All non-high-risk (non-HR) patients received the same dose. HR-patients received additional Erwinase, with three doses at 2-day intervals in each treatment block. Activity levels are available from \~150 patients; among these, 20 patients received more than six doses (range: 7-42). In the A2G-1, Erwinase was administered intravenously (IV) at 20,000 IU/m², substituting one PEG-asparaginase dose with seven Erwinase doses every other day. The number of doses received varied depending on the timing of hypersensitivity reactions. Activity levels are already available from \>90 patients. Measurement of Erwinase enzyme activity levels is performed at the Asparaginase Lab in Aarhus. All samples have been analysed. The data will undergo further cleaning, validation, followed by integration with patient characteristics in a population PK model. Data Management and Security in Uppsala: All PK data will be pseudo-anonymized before being securely transferred to Uppsala University through the Allvis data portal. Data handling and formatting will be scripted in R to ensure transparency and reproducibility. Modelling will be performed on the UPPMAX computing cluster via the Swedish National Academic Infrastructure for Supercomputing. Workflow, statistics and perspectives: The modelling workflow will be performed as follows: 1. A PK model for Erwinase will be established based on asparaginase enzyme activity TDM data obtained from Nordic/Baltic ALL patients treated under the NOPHO and A2G-1. Drug clearance, volume of distribution, absorption, and bioavailability will be derived to describe the PK of both routes of Erwinase administration (IV vs IM). Nonlinear mixed-effects modelling will be applied to obtain both typical population PK parameters as well as patient variability parameters. Potential changes in parameters within patients over time will also be explored. Model development and evaluation will be conducted using NONMEM17. Model selection will be based on statistical fit and biological plausibility. Goodness of fit plots and visual predictive checks will ensure the PK model adequately describes the observed data. 2. The Erwinase PK model will be applied to explore alternative dosing strategies, as simultaneously achieving aimed target attainment (≥100 IU/L).

A Study to Find the Highest Dose of SNDX-5613 (Revumenib) as a Treatment Option After Hematopoietic Stem Cell Transplant in Children With Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, and Mixed Phenotype Acute Leukemia

This phase I trial tests the safety, best dose, and effectiveness of revumenib given as maintenance therapy after standard hematopoietic stem cell transplant (HSCT) in patients with acute lymphoblastic leukemia, acute myeloid leukemia, or mixed phenotype acute leukemia. Revumenib binds to a protein called menin, which prevents menin from interacting with another protein called MLL. This results in an inhibition of the proliferation of leukemic cells with certain genetic alterations. Revumenib may inhibit the survival, growth, transformation and proliferation of certain kinds of leukemia cells. It is approved for the treatment of patients with certain types of acute leukemia, but it is not approved for maintenance therapy (treatment that aims to prevent cancer from coming back) after HSCT.

A Vaccine (CMV-MVA Triplex Vaccine) for the Enhancement of CMV-Specific Immunity and the Prevention of CMV Viremia in Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplant

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.

Biology Studies of Hematologic Cancers

This study will collect tumor samples from people with cancers of the blood, bone marrow, or lymph glands for laboratory study of the biology of these conditions. Such studies contribute to a better understanding of cancer biology and to the development of new treatments. Planned studies include: * Examination of individual cancer cells and to search for differences compared to other types of cancer and normal cells * Examination of the chromosomes and genes in cancer cells and to search for differences compared to other types of cancer and normal cells * Development of sensitive methods to detect small amounts of cancer that remain after treatment * Search for new cancer proteins that might serve as targets for treatment * Investigation of methods to develop cancer vaccines. Patients from \>= 1 to 75 years of age with acute lymphocytic leukemia, acute myelogenous leukemia, myelodysplastic syndrome, chronic myelogenous leukemia, juvenile myelomonocytic leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, and other hematologic malignancies may be eligible for this study. Blood or bone marrow samples will be collected when sampling is required for the patient's medical care. Cells from some individuals will be grown in test tubes, establishing cell lines or in animals, establishing xenograft models. (A xenograft is transplantation of cells of one species to another species.)

CAR T CELL Therapy for Pediatric, Adolescent and Young Adult Patients With CD19-Positive Leukemia

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.

MB-CART19.1 in Relapsed/Refractory Acute Lymphoblastic Leukemia

Single-arm, prospective, open-label feasibility study evaluating the technical and operational feasibility of manufacturing autologous CD19-directed CAR-T cells (MB-CART19.1) at the point of care for the treatment of relapsed or refractory B-ALL in pediatric and adult patients.

Expanded/Activated Gamma Delta T-cell Infusion Following Hematopoietic Stem Cell Transplantation and Post-transplant Cyclophosphamide

Gamma delta T-cells are part of the innate immune system with the ability to recognize malignant cells and kill them. This study uses gamma delta T-cells to maximize the anti-tumor response and minimize graft versus host disease (GVHD) in leukemic and myelodysplastic patients who have had a partially mismatched bone marrow transplant (haploidentical).

A Study of Obecabtagene Autoleucel in People With B-cell Acute Lymphoblastic Leukemia

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).