Cyclophosphamide Treatment Options

Phase 1 open-label study to evaluate the safety of intravenously administered, lentivirally transduced T cells expressing anti-CD123 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains in pediatric subjects with relapsed/refractory Acute Myeloid Leukemia (AML). Read Less

Background: - Some sickle cell disease or beta-thalassemia can be cured with transplant. Researchers want to test a variation of transplant that uses low dose radiation and a combination of immunosuppressive drugs. They want to know if it helps a body to better accept donor stem cells. Objectives: - To see if low dose radiation (300 rads), oral cyclophosphamide, pentostatin, and sirolimus help a body to better accept donor stem cells. Eligibility: - People 4 and older with beta-thalassemia or sickle cell disease that can be cured with transplant, and their donors. Design: * Participants and donors will be screened with medical history, physical exam, blood test, tissue and blood typing, and bone marrow sampling. They will visit a social worker. * Donors: * may receive an intravenous (IV) tube in their groin vein. * will receive a drug injection daily for 5 or 6 days to move the blood stem cells from the bone marrow into general blood circulation. * will undergo apheresis: an IV is put into a vein in each arm. Blood is taken from one arm, a machine removes the white blood cells that contain blood stem cells, and the rest is returned through the other arm. * Participants: * may undergo red cell exchange procedure. * will remain in the hospital for about 30 days. * will receive a large IV line that can stay in their body from transplant through recovery. * will receive a dose of radiation, and transplant related drugs by mouth or IV. * will receive blood stem cells over 8 hours by IV. * will take neuropsychological tests and may complete questionnaires throughout the transplant process. * must stay near NIH for 4 months. They will visit the outpatient clinic weekly. Read Less

This phase II trial studies how well administering ruxolitinib before, during, and after allogeneic hematopoietic stem cell transplantation works in preventing graft versus host disease and improving transplant outcomes in patients with primary and secondary myelofibrosis. Donor hematopoietic stem cell transplantation (HSCT) is currently the only treatment with proven curative potential for myelofibrosis, however, myelofibrosis patients have a high risk for developing graft versus host disease post-transplant. Graft versus host disease is a condition where the transplanted cells from a donor can attack the body's normal cells. Ruxolitinib, a janus-associated kinase (JAK) inhibitor, is known to decrease inflammatory signals, which may reduce spleen size and decrease symptoms such as night sweats and weight loss. Administering ruxolitinib before, during, and after transplant may decrease the incidence and severity of graft versus host disease, increase survival, and improve quality of life in patients with primary and secondary myelofibrosis. Read Less

This phase I/Ib trial studies the side effects and best dose of parsaclisib with or without polatuzumab-vedotin (Pola) plus the standard drug therapy (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone \[PaR-CHOP\]) and to see how well they work compared with R-CHOP alone in treating patients with newly diagnosed, high risk diffuse large B-cell lymphoma. Parsaclisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Polatuzumab-vedotin is a monoclonal antibody, called polatuzumab, linked to a chemotherapy drug, called vedotin. Polatuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as anti-CD79b receptors, and delivers vedotin to kill them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, and vincristine sulfate, 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. Anti-inflammatory drugs, such as prednisone, lower the body's immune response and are used with other drugs in the treatment of some types of cancer. It is not yet known if giving parsaclisib and R-CHOP together works better than R-CHOP alone in treating patients with high risk diffuse large B-cell lymphoma. Read Less

Cord blood (CB) transplants are an option for patients lacking an HLA identical donor but are hampered by low cell dose, prolonged aplasia and high transplant related mortality. UM171, a novel and potent agonist of hematopoietic stem cell self renewal could solve this major limitation, allowing for CB's important qualities as lower risk of chronic GVHD and relapse to prevail. In previous trials (NCT02668315, NCT03913026, NCT04103879, and NCT03441958), the CB expansion protocol using the ECT-001-CB technology (UM171 molecule) has proven to be technically feasible and safe in adults. UM171 expanded CB was associated with a prompt (D+17), robust (98%) and durable neutrophil recovery. Amongst patients who received a single UM171 CB transplant with a median follow-up of 18 months, risk of TRM (10%), grade 3-4 acute GVHD (13%) and moderate-severe chronic GVHD (2%) was low at 1 year post-transplant. Incidence of severe viral and bacterial infections was reduced and immunosuppression could be discontinued in 77% of patients at 1 year. Thus, PFS and GRFS were very promising, 72% and 59% at 12 months, 69% and 53% at 24 months, respectively, in particular accounting for a large proportion of very high-risk patients. By a 10-fold increase of CB accessibility, ECT-001-CB allowed access to smaller, better HLA matched CBs. This new study seeks to test a similar strategy in a group of pediatric and young adult patients with high risk myeloid malignancies. 12 patients will be enrolled in the first stage of this 2-stage design protocol. If intervention is considered promising (\<= 3 relapses in the first 12 patients), this study will open multicenter and be extended to a second stage (16 additional patients for a total accrual 28). Read Less

This phase II trial investigates two strategies and how well they work for the reduction of graft versus host disease in patients with acute leukemia or MDS in remission. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also 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. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells. Read Less

Subjects that have relapsed or refractory neuroblastoma are invited to take part in this gene transfer research study. We have found from previous research that we can put a new gene called a chimeric antigen receptor (CAR) into T cells that will make them recognize neuroblastoma cells and kill them. In a previous clinical trial, we used a CAR that recognizes GD2, a protein found on almost all neuroblastoma cells (GD2-CAR). We put this gene into T cells and gave them back to patients that had neuroblastoma. The infusions were safe and in patients with disease at the time of their infusion, the time to progression was longer if we could find GD2 T cells in their blood for more than 6 weeks. Because of this, we think that if T cells are able to last longer, they may have a better chance of killing neuroblastoma tumor cells. Therefore, in this study we will add new genes to the GD2 T cells that can cause the cells to live longer. These new genes are called CD28 and OX40. The purpose of this study will be to determine the highest dose of iC9-GD2-CD28-OX40 (iC9-GD2) T cells that can safely be given to patients with relapsed/refractory neuroblastoma. In other clinical studies using T cells, some investigators found that giving chemotherapy before the T cell infusion can improve the amount of time the T cells stay in the body and therefore the effect the T cells can have. This is called lymphodepletion and we think that it will allow the T cells we infuse to expand and stay longer in the body, and potentially kill cancer cells more effectively. The chemotherapy we will use for lymphodepletion is a combination of cyclophosphamide and fludarabine. Additionally, to effectively kill the tumor cells, it is important that the T cells are able to survive and expand in the tumor. Recent studies have shown that solid tumors release a substance (PD1) that can inhibit T cells after they arrive into the tumor tissue. In an attempt to overcome the effect of PD1 in neuroblastoma we will also give a medication called pembrolizumab. Read Less

To learn if the study drug golidocitinib given alone or in combination with the standard drug combination therapy called CHOP can help to control PTCL. Read Less

Patients less than or equal to 21 years old with high-risk hematologic malignancies who would likely benefit from allogeneic hematopoietic cell transplantation (HCT). Patients with a suitable HLA matched sibling or unrelated donor identified will be eligible for participation ONLY if the donor is not available in the necessary time. The purpose of the study is to learn more about the effects (good and bad) of transplanting blood cells donated by a family member, and that have been modified in a laboratory to remove the type of T cells known to cause graft-vs.-host disease, to children and young adults with a high risk cancer that is in remission but is at high risk of relapse. This study will give donor cells that have been TCRαβ-depleted. The TCR (T-cell receptor) is a molecule that is found only on T cells. These T-cell receptors are made up of two proteins that are linked together. About 95% of all T-cells have a TCR that is composed of an alpha protein linked to a beta protein, and these will be removed. This leaves only the T cells that have a TCR made up of a gamma protein linked to a delta protein. This donor cell infusion will be followed by an additional infusion of donor memory cells (CD45RA-depleted) after donor cell engraftment. This study will be testing the safety and effects of the chemotherapy and the donor blood cell infusions on the transplant recipient's disease and overall survival. Read Less

This study enrolls patients who have a type of cancer that arises from the liver called hepatocellular carcinoma. The cancer has come back, has not gone away after standard treatment, has spread outside of the liver or the patient cannot receive standard treatment. This research study uses special immune system cells called GLYCAR T cells, a new experimental treatment. The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: antibodies and T cells. Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. They have shown promise, but have not been strong enough to cure most patients. Investigators have found from previous research that they can put a new gene into T cells that will make them recognize cancer cells and kill them. In preclinical studies, the investigators made several genes called a chimeric antigen receptor (CAR), from an antibody called GC33 that recognizes glypican-3, a protein found on almost all hepatocellular carcinoma cells (GPC3-CAR). This study will test T cells genetically engineered with a GPC3-CAR (GLYCAR T cells) in patients with hepatocellular carcinoma. The GLYCAR T cells are an investigational product not approved by the Food and Drug Administration. The purpose of this study is to find the biggest dose of GLYCAR T cells that is safe, to see how long they last in the body, to learn what the side effects are and to see if the GLYCAR T cells will help people with GPC3-positive hepatocellular carcinoma. Read Less

QUILT 3.091 Chordoma Vaccine: Phase 1B/2 NANT Chordoma Vaccine vs Radiation in Subjects with Unresectable Chordoma. Read Less

Unfortunately, some patients with Crohn's disease (CD) fail to respond to the best clinical treatments and some only experience temporary benefit. For severe Crohn's disease, there is an experimental treatment called "high dose immunoablation" followed by autologous hematopoietic stem cell transplantation (HSCT). This study removes over active lymphocytes (immunoablation) and replaces them using blood stem cells that have been taken from the patient's own body. The aim of the study is to reset or reprogram the patient's immune system to its state prior to diagnosis. Read Less