Clinical Research Directory

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....

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.

Personalized NK Cell Therapy in CBT

This phase II clinical trial studies how well personalized natural killer (NK) cell therapy works after chemotherapy and umbilical cord blood transplant in treating patients with myelodysplastic syndrome, leukemia, lymphoma or multiple myeloma. This clinical trial will test cord blood (CB) selection for human leukocyte antigen (HLA)-C1/x recipients based on HLA-killer-cell immunoglobulin-like receptor (KIR) typing, and adoptive therapy with CB-derived NK cells for HLA-C2/C2 patients. Natural killer cells may kill tumor cells that remain in the body after chemotherapy treatment and lessen the risk of graft versus host disease after cord blood transplant.

huCART19-IL18-CD428z Cells for the Treatment of Patients With HIV With CD19+ Cancers

This research study is being conducted to evaluate an experimental drug called huCART19-IL18-CD428z cells in patients living with HIV who have been diagnosed with Non-Hodgkin Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), Acute Lymphoblastic Leukemia (ALL), and Richter's Transformation (RT).

Expanded Access Study for the Treatment of Patients With Commercially Out-of-Specification Brexucabtagene Autoleucel

The goal of this study is to provide access to brexucabtagene autoleucel for patients diagnosed with a disease approved for treatment with brexucabtagene autoleucel, that is otherwise out of specification for commercial release.

225Ac-DOTA-Anti-CD38 Daratumumab Monoclonal Antibody With Fludarabine, Melphalan and Total Marrow and Lymphoid Irradiation as Conditioning Treatment for Donor Stem Cell Transplant in Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia and Myelodysplastic Syndrome

This phase I trial tests the safety, side effects, best dose, and effectiveness of 225Ac-DOTA-Anti-CD38 daratumumab monoclonal antibody in combination with fludarabine, melphalan and total marrow and lymphoid irradiation (TMLI) as conditioning treatment for donor stem cell transplant in patients with high-risk acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and myelodysplastic syndrome (MDS). Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Radioimmunotherapy is treatment with a radioactive substance that is linked to a monoclonal antibody, such as daratumumab, that will find and attach to cancer cells. Radiation given off by the radioisotope my help kill the cancer cells. Chemotherapy drugs, such as fludarabine and melphalan, 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. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. TMLI is a targeted form of body radiation that targets marrow, lymph node chains, and the spleen. It is designed to reduce radiation-associated side effects and maximize therapy effect. Actinium Ac 225-DOTA-daratumumab combined with fludarabine, melphalan and TMLI may be safe, tolerable, and/or effective as conditioning treatment for donor stem cell transplant in patients with high-risk AML, ALL, and MDS.

A Clinical Study of MK-1045 (CN201) in People With Precursor B-cell Acute Lymphoblastic Leukemia (MK-1045-002)

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.

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.

High-Intensity Parent Intervention Program in Improving Learning and School Functioning in Latino Children With Acute Leukemia or Lymphoblastic Lymphoma

This randomized clinical trial studies how well a high-intensity intervention parenting program works in improving learning and school functioning in Latino children with acute leukemia or lymphoblastic lymphoma. A high-intensity intervention program may help doctors to see whether training parents or caregivers in specific parenting skills and "pro-learning" behaviors will result in better learning and school outcomes for Latino children with acute leukemia or lymphoblastic lymphoma. It is not yet known if a high-intensity intervention program is more beneficial than a standard of care lower intensity parenting intervention.

SPARK-ALL: Calaspargase Pegol in Adults With ALL

The purpose of this phase 2/3 study is to confirm the recommended doses and to evaluate the safety and pharmacodynamics of Calaspargase pegol for the treatment of adult patients with Philadelphia-negative Acute Lymphoblastic Leukemia.

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).

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.

Alpha/Beta CD19+ Depleted Haploidentical Transplantation + Zometa for Pediatric Hematologic Malignancies and Solid Tumors

This phase I trial studies the safety of transplantation with a haploidentical donor peripheral blood stem cell graft depleted of TCRαβ+ cells and CD19+ cells in conjunction with the immunomodulating drug, Zoledronate, given in the post-transplant period to treat pediatric patients with relapsed or refractory hematologic malignancies or high risk solid tumors.

A Study of Sonrotoclax (BGB-11417) in Children With Relapsed or Refractory Acute Myeloid Leukemia and B-cell Acute Lymphoblastic Leukemia

The goal of this clinical trial is to learn if sonrotoclax (BGB-11417) is safe and may help treat children and adolescents with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) that has come back after treatment or has not responded to treatment. The study will also learn how the body processes sonrotoclax when it is given with other medicines. The main questions it aims to answer are: * Is sonrotoclax safe and well tolerated when given with other anti-cancer medicines? * How does the body absorb, process, and remove sonrotoclax? * Does treatment with sonrotoclax, in combination with other medicines, help reduce or eliminate leukemia? Researchers will give sonrotoclax together with other anti-cancer medicines to participants with relapsed or refractory AML or ALL. Participants will: * Take sonrotoclax in combination with other anti-cancer medicines * Have regular clinic visits for physical exams, blood tests, heart monitoring, and other safety assessments. * Provide blood samples to measure how the body processes sonrotoclax. * Have tests to evaluate how their leukemia responds to treatment. * Continue treatment as long as it is helping and side effects remain manageable, according to the study plan.

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....

Pharmacokinetics of Dexamethasone in Childhood ALL and Reduction in Bone Mineral Density

The goal of this observational study is to learn about systemic and central nervous system (CNS) exposure to dexamethasone in childhood acute lymphoblastic leukaemia (ALL). The main questions it aims to answer are: * How does the intake of dexamethasone correlate with systemic exposure to dexamethasone in blood? * How does systemic exposure to dexamethasone correlate with dexamethasone concentrations in cerebrospinal fluid (CSF)? * Is dexamethasone exposure in blood and CSF associated with clearance of leukemic CNS infiltration? * Does systemic and/or CNS exposure to dexamethasone correlate with neurotoxicity as assessed by questionnaires? * Does systemic exposure to dexamethasone correlate with a reduction in bone mineral density? Participants will: * Continue to receive the best available therapy for ALL in Western Europe. * Have blood samples taken from their central line to measure dexamethasone levels. * When standard lumbar punctures are performed as part of treatment, an additional sample of cerebrospinal fluid will be collected to analyse dexamethasone concentrations and assess leukemic CNS involvement when applicable. * Visit the clinic four times for DXA scans to measure bone density and perform vertebral fracture assessment: within three weeks of starting treatment, six months after starting treatment, one month after finishing treatment, and one year after finishing treatment. Biomarkers related to bone health will also be collected on these days. * Complete validated questionnaires to monitor neurotoxicity and to track daily physical activity levels during treatment.

Cord Blood Transplant, Cyclophosphamide, Fludarabine, and Total-Body Irradiation in Treating Patients With High-Risk Hematologic Diseases

This phase II trial studies how well giving an umbilical cord blood transplant together with cyclophosphamide, fludarabine, and total-body irradiation (TBI) works in treating patients with hematologic diseases. Giving chemotherapy, such as cyclophosphamide, fludarabine and thiotepa, and TBI before a donor cord blood transplant (CBT) helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after transplant may stop this from happening in patients with high-risk hematologic diseases.

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.

CMV-MVA Triplex Vaccination in HLA-Matched Related Stem Cell Donors for the Prevention of CMV Infection in Patients Undergoing Hematopoietic Stem Cell Transplant

This phase II clinical trial tests how well the cytomegalovirus-modified vaccinica Ankara (CMV-MVA) Triplex vaccine given to human leukocyte antigens (HLA) matched related stem cell donors works to prevent cytomegalovirus (CMV) infection in patients undergoing hematopoietic stem cell transplant. The CMV-MVA Triplex vaccine works by causing an immune response in the donors body to the CMV virus, creating immunity to it. The donor then passes that immunity on to the patient upon receiving the stem cell transplant. Giving the CMV-MVA triplex vaccine to donors may help prevent CMV infection of patients undergoing stem cell transplantation.

Prevention of Oral Mucositis in Adults in With Hematologic Malignancy

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.

A Study of Blinatumomab in Patients With Pre B-cell ALL and B-cell NHL as Post-allo-HSCT Remission Maintenance

The investigators primary objective is to determine the safety and toxicity of incorporating blinatumomab into the post-allogeneic hematopoietic stem cell transplant (HSCT) maintenance setting for patients with CD19+-B-cell malignancies (Acute Lymphoblastic Leukemia \[ALL\], Non-Hodgkin's Lymphoma \[NHL\]).

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).