52 Clinical Trials for Various Conditions
The goal of this clinical research study is to learn if intermediate-intensity conditioning therapy followed by a cord blood transplant can help to control high-risk hematological malignancies in patients who need a second allogeneic stem cell transplantation.
Background: People with blood cancers often receive blood or bone marrow transplants. But even with these treatments, the risk of relapse is high. Researchers want to see if giving the transplant recipient an infusion of lymphocytes (a type of white blood cell) from their transplant donor early after the transplant can reduce that risk. Objective: To learn if giving donor lymphocytes early after a transplant will help reduce the risk of relapse for people with certain blood cancers. Eligibility: Adults aged 18-65 with high-risk leukemia, lymphoma, myelodysplastic syndrome, or multiple myeloma that does not respond well to standard treatments and/or has a high risk of relapse. Healthy potential bone marrow and lymphocyte donor relatives aged 12 and older are also needed. Design: Participants will be screened with: Physical exam Blood and urine tests Spinal tap Eye exam Dental exam Heart and lung tests Imaging scans. A radioactive substance may be injected in their arm if a PET scan is needed. Bone marrow aspiration and biopsy Some screening tests will be repeated during the study. Participants will stay at the NIH hospital for about 4 weeks. They will receive a central venous catheter. They will get chemotherapy and other drugs starting 6 days before transplant. Then they will have their transplant. They will receive donor white blood cells 7 days later. They will give blood, bone marrow, urine, and stool samples for research. They must stay near NIH for at least 100 days after transplant. Participants will have periodic follow-up visits for 5 years. Healthy donors will have 2-3 visits. They will give blood, bone marrow, white blood cells, and stool samples for research. Participation will last for 5 years....
This trial is evaluating the safety and tolerability of venetoclax with chemotherapy in pediatric and young adult patients with hematologic malignancies, including myelodysplastic syndrome (MDS), acute myeloid leukemia derived from myelodysplastic syndrome (MDS/AML), and acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL). The names of the study drugs involved in this study are below. Please note this is a list for the study as a whole, participants will receive drugs according to disease cohort. * Venetoclax * Azacitidine * Cytarabine * Methotrexate * Hydrocortisone * Leucovorin * Dexamethasone * Vincristine * Doxorubicin * Dexrazoxane * Calaspargase pegol * Hydrocortisone
This phase Ib trial studies the toxicity and dosing of venetoclax in combination with selinexor, and how well the combination works in treatment of patients with high risk hematologic malignancies such as diffuse large B-cell lymphoma and acute myeloid leukemia that has come back (recurrent) or does not respond to initial treatment (refractory). Venetoclax functions by inhibiting a protein in the body called bcl-2, which is involved in slowing down the normal process by which old cells in the body are cleared (called apoptosis). Selinexor functions by trapping "tumor suppressing proteins" within the cell and causing the cancer cells to die or stop growing. This study examines the effects, if any, of selinexor and venetoclax on high risk hematologic malignancies and on the body, including any side-effects.
This pilot clinical trial aims to assess feasibility and tolerability of using an LINAC based "organ-sparing marrow-targeted irradiation" to condition patients with high-risk hematological malignancies who are otherwise ineligible to undergo myeloablative Total body irradiation (TBI)-based conditioning prior to allogeneic stem cell transplant. The target patient populations are those with ALL, AML, MDS who are either elderly (\>50 years of age) but healthy, or younger patients with worse medical comorbidities (HCT-Specific Comorbidity Index Score (HCT-CI) \> 4). The goal is to have the patients benefit from potentially more efficacious myeloablative radiation based conditioning approach without the side effects associated with TBI.
This phase II trial studies how well total-body irradiation, donor lymphocyte infusion, and cyclophosphamide before donor stem cell transplant works in treating patients with high-risk hematologic malignancies. Giving total-body irradiation, donor lymphocyte infusion, and chemotherapy before a donor stem cell transplant 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 certain 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. Removing the T cells from the donor cells before transplant and giving tacrolimus and mycophenolate mofetil may stop this from happening.
Open label, dose finding trial to assess the efficacy of Treg/Tcon addback to partially matched related donor stem cells. The maximum tolerated dose will be established using 3 subjects per dose level, with an expansion cohort at the maximum tolerated dose.
This phase II trial studies reduced-intensity conditioning before donor stem cell transplant in treating patients with high-risk hematologic malignancies. Giving low-doses of chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop 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). Giving an infusion of the donor's T cells (donor lymphocyte infusion) before the transplant may help increase this effect.
This study will determine the safety and applicability of experimental forms of umbilical cord blood (UCB) transplantation for patients with high risk hematologic malignancies who might benefit from a hematopoietic stem cell transplant (HSCT) but who do not have a standard donor option (no available HLA-matched related donor (MRD), HLA-matched unrelated donor (MUD)), or single UCB unit with adequate cell number and HLA-match).
The purpose of this research study is to examine the survival of patients undergoing partially matched hematopoietic stem cell transplant (HSCT) on a new type of treatment approach, which has been developed specifically for patients who have evidence of their disease at the time of transplant. In this research study, a way of strengthening the response of the donor cells against the disease has been developed. Patients will undergo one additional day between the two steps of the transplant which may allow their donor's cells to fight the disease more effectively.
This phase I clinical trial is studying the side effects and the best dose of lenalidomide after donor bone marrow transplant in treating patients with high-risk hematologic cancer. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing.
RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop 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). PURPOSE: This phase I trial is studying the safety of donor umbilical cord blood transplant after fludarabine phosphate, cyclophosphamide, and total-body irradiation in treating patients with high-risk hematologic cancer (now closed). The Phase II part of this trial is studying whether priming one of two UCB units with C3a facilitates engraftment of the treated unit.
RATIONALE: Giving low doses of chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop 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). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving a monoclonal antibody, such as alemtuzumab, before transplant and tacrolimus and methotrexate after transplant may stop this from happening. PURPOSE: This phase II trial is studying the side effects of donor stem cell transplant and to see how well it works in treating patients with high-risk hematologic cancer.
RATIONALE: A donor peripheral stem cell transplant helps stop the growth of cancer 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. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them. Giving an infusion of donor T cells may helps stop the patient's immune system from rejecting the donor's stem cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of donor T cells in treating patients with high-risk hematologic cancer who are undergoing donor peripheral blood stem cell transplant. Note: Only Phase I portion of study was performed. Due to slow accrual, study was closed before Phase II portion of study.
Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner. Another option is haploidentical transplant using a partially matched family member donor. Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including GVHD and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the body tissues of the patient (the host) are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for significant infection. For these reasons, a primary focus for researchers is to engineer the graft to provide a T cell dose that will reduce the risk for GVHD, yet provide a sufficient number of cells to facilitate immune reconstitution and graft integrity. Building on prior institutional trials, this study will provide patients with a haploidentical (HAPLO) graft engineered to specific T cell target values using the CliniMACS system. A reduced intensity, preparative regimen will be used in an effort to reduce regimen-related toxicity and mortality. The primary aim of the study is to help improve overall survival with haploidentical stem cell transplant in this high risk patient population by 1) limiting the complication of graft versus host disease (GVHD), 2) enhancing post-transplant immune reconstitution, and 3) reducing non-relapse mortality.
The purpose of the study is to conduct a phase I study of adoptive immunotherapy with autologous, ex-vivo expanded cytokine-induced killer (CIK) cells to reduce the relapse rate in autologous stem cell transplant patients with high-risk hematologic malignancies.
The purpose of this study is to determine the efficacy and safety of transplanting StemEx® in patients with certain hematological malignancies. For these patients, it is suggested that StemEx® can improve upon the outcome of transplanting a single, unmanipulated cord blood unit by significantly increasing the number of stem/progenitor cells available to the patient.
This study will determine the safety and effectiveness of an experimental vaccine in controlling the abnormal growth of cells in patients with myelodysplastic syndrome (MDS, also known as myelodysplasia), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML). It will test whether the vaccine can increase the number of immune cells responding to the cancer and thereby slow progression of the illness, improve blood counts, reduce the need for transfusions of blood and platelets, or even achieve a disease remission. The vaccine contains part of a protein that is produced in large amounts by cells of patients with these cancers and an added substance called Montanide that helps the immune system respond to the vaccine. Sargramostim, another substances that boosts the immune response, is also given. Patients 18 to 85 years of age with MDS, AML, ALL or CML may be eligible for this study. Candidates are screened with a medical history, physical examination, blood tests, chest x-ray and bone marrow biopsy. Women of childbearing age also have a pregnancy test. Participants undergo the following: * Chemotherapy entering the study. * Leukapheresis to collect large amounts of white blood cells for infusion before vaccine administration. * Participants may need placement of a central line (plastic tube, or catheter) in the upper part of the chest to be used for giving chemotherapy, blood or platelet transfusions, antibiotics and white blood cells, and for collecting blood samples. * Weekly vaccine injections for nine weeks, given in the upper arm, upper leg or abdomen. * Sargramostim injections following each vaccination. * Standard of care treatment for MDS, AML, ALL or CML, which may include blood or platelet transfusions, growth factors, and drugs to control underlying disease and potential side effects of the vaccine. * Weekly safety monitoring, including vital signs check, brief health assessment, blood tests and observation after the vaccination, on the day of each vaccination. * Follow-up evaluations with blood tests and chest x-ray 3 weeks after the last vaccine dose and with blood tests and bone marrow biopsy 7 weeks after the last vaccine dose.
This phase II trial studies how well giving fludarabine phosphate, cyclophosphamide, tacrolimus, mycophenolate mofetil and total-body irradiation together with a donor bone marrow transplant works in treating patients with high-risk hematologic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate and cyclophosphamide, and total-body irradiation before a donor bone marrow transplant helps stop the growth of cancer cells by stopping them from dividing or killing them. Giving cyclophosphamide after transplant may also stop the patient's immune system from rejecting the donor's bone marrow stem cells. The donated stem cells may replace the patient's immune system cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil after the transplant may stop this from happening
RATIONALE: Umbilical cord blood transplantation may allow doctors to give higher doses of chemotherapy or radiation therapy and kill more cancer cells. PURPOSE: This phase II trial is studying allogeneic umbilical cord blood transplantation to see how well it works when given with chemotherapy or radiation therapy in treating patients with high-risk hematologic cancer.
This is a multi-center Phase I/II clinical trial of GTB-3550 (CD16/IL-15/CD33) tri-specific killer cell engager (TriKE®) for the treatment of CD33-expressing high risk myelodysplastic syndromes, refractory/relapsed acute myeloid leukemia or advanced systemic mastocytosis. The hypothesis is that GTB-3550 TriKE® will induce natural killer cell function by targeting malignant cells as well as CD33+ myeloid derived suppressor cells (MDSC) which contribute to tumor induced immunosuppression. Because CD16 is the most potent activating receptor on natural killer (NK) cells, this single agent may induce a targeted anti-CD33+ tumor response.
This is study is for patients that have been diagnosed with high-risk hematological malignancies. The main purpose of this study is to confirm previously published results of stem cell transplantation with reduced intensity pre-transplant conditioning. Patients will be assigned to 1 of 3 regimens depending on the patient's diagnosis. Participants will be followed by the transplant team for the remainder of the patient's life. Patient's will visit MUSC daily, then visits will be reduced to frequent visits for up to 6 months. After 6 months, the visits will be reduced more depending on the patient's condition.
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 a previous trial (NCT02668315), the CB expansion protocol using the ECT-001-CB technology (UM171 molecule) has proven to be technically feasible and safe. UM171 expanded CB was associated with a median neutrophil recovery at day (D)+18 post transplant. Amongst 22 patients who received a single UM171 CB transplant with a median follow-up of 18 months, risk of TRM (5%) and grade 3-4 acute GVHD (10%) were low. There was no moderate-severe chronic GVHD. Thus, overall and progression free survival at 12 months were impressive at 90% and 74%, respectively. The UM171 expansion protocol allowed access to smaller, better HLA matched CBs as \>80% of patients received a 6-7/8 HLA matched CB. Interestingly there were patients with high-risk hematologic malignancies and multiple comorbidities (5 patients who had already failed an allogeneic transplant and 5 patients with refractory/relapsed acute leukemia/aggressive lymphoma). Despite this high risk population, progression was 20% at 12 months. This new study seeks to test a similar strategy in a group of patients with high risk acute leukemia/myelodysplasia.
The purpose of this study is to investigate whether the combination of cyclophosphamide and abatacept versus the treatment used in standard of care will reduce the incidence of moderate and severe chronic graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation. GVHD occurs when the cells from your donor (the graft) see your body's cells (the host) as different and attack them.
Childhood leukemias which cannot be cured by chemotherapy alone may be effectively treated by allogeneic bone marrow transplantation. Moreover, for patients with chronic myelogenous leukemia (CML), allogeneic hematopoietic stem cell transplantation (HSCT) is the only proven curative modality of treatment. Patients who have received hematopoietic stem cells from an HLA matched sibling donor have proven to be less at risk for disease relapse and regimen related toxicity. However, about 70% of patients in need of HSCT do not have an HLA matched sibling donor. This necessitates the search for alternative donors, which may increase the risk of a poor outcome. The nature of the hematopoietic stem cell graft has been implicated as a primary factor determining these outcomes. The standard stem cell graft has been unmanipulated bone marrow, but recently several advantages of T-lymphocyte depleted bone marrow and mobilized peripheral blood progenitor cells (PBPC) have been demonstrated. However, T-cell depletion may increase the risk of infectious complications and leukemic recurrence while an unmanipulated stem cell graft may increase the risk of graft vs. host disease (GVHD). A key element in long range strategies in improving outcomes for patients undergoing matched unrelated donor (MUD) HSCT is to provide the optimal graft. The primary objective of this clinical trial is to estimate the incidence of acute GVHD in pediatric patients with hematologic malignancies who receive HSCT with an unmanipulated marrow graft. The results of this study can be used as the foundation for future trials related to engineering unrelated donor graft.
Relapsed disease is the most common cause of death in children with hematological malignancies. Patients who fail high-intensity conventional chemotherapeutic regimens or relapse after stem cell transplantation have a poor prognosis. Toxicity from multiple therapies and elevated leukemic/tumor burden usually make these patients ineligible for the aggressive chemotherapy regimens required for conventional stem cell transplantation. Alternative options are needed. One type of treatment being explored is called haploidentical transplant. Conventional blood or bone marrow stem cell transplant involves destroying the patient's diseased marrow with radiation or chemotherapy. Healthy marrow from a donor is then infused into the patient where it migrates to the bone marrow space to begin generating new blood cells. The best type of donor is a sibling or unrelated donor with an identical immune system (HLA "match"). However, most patients do not have a matched sibling available and/or are unable to identify an acceptable unrelated donor through the registries in a timely manner. In addition, the aggressive treatment required to prepare the body for these types of transplants can be too toxic for these highly pretreated patients. Therefore doctors are investigating haploidentical transplant using stem cells from HLA partially matched family member donors. Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including graft versus host disease (GVHD), and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the patient's (the host) body tissues are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for infection. However, the presence of T cells in the graft may offer a positive effect called graft versus malignancy or GVM. With GVM, the donor T cells recognize the patient's malignant cells as diseased and, in turn, attack these diseased cells. For these reasons, a primary focus for researchers is to engineer the graft to provide a T cell depleted product to reduce the risk of GVHD, yet provide a sufficient number of cells to facilitate immune reconstitution, graft integrity and GVM. In this study, patients were given a haploidentical graft engineered to with specific T cell parameter values using the CliniMACS system. A reduced intensity, preparative regimen was used to reduce regimen-related toxicity and mortality. The primary goal of this study is to evaluate overall survival in those who receive this study treatment.
Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner. Another option is haploidentical transplant using a partially matched family member donor. Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including GVHD and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the body tissues of the patient (the host) are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for significant infection. For these reasons, a primary focus for researchers is to engineer the graft to provide a T cell dose that will reduce the risk for GVHD, yet provide a sufficient number of cells to facilitate immune reconstitution and graft integrity. Building on prior institutional trials, this study will provide patients with a haploidentical graft engineered to specific T cell target values using the CliniMACS system. A reduced intensity, preparative regimen will be used in an effort to reduce regimen-related toxicity and mortality. Two groups of patients were enrolled on this study. One group included those with high-risk hematologic malignancies and the second group included participants with refractory hematologic malignancies or undergoing a second transplant. The primary aim of the study was to estimate the relapse rate in the one group of research participants with refractory hematologic malignancies or those undergoing second allogeneic transplant. Both groups will be followed and analyzed separately in regards to the secondary objectives. This study was closed to accrual on April 2006 as it met the specific safety stopping rules regarding occurrence of severe graft vs. host disease. Although this study is no longer open to accrual, the treated participants continue to be followed as directed by the protocol.
Although a majority of children with leukemia and most hematological malignancies (Hodgkin's and Non-Hodgkin's lymphomas) can be cured with conventional chemotherapy, a subset of patients with resistant/recurrent high-risk disease are not cured with conventional treatment regimens. Investigators hypothesize that HSCT from a partially matched donor can be safe and effective for patients with very high risk hematologic malignancies when combined with post-transplant cyclophosphamide for prevention of graft-vs-host disease (GVHD).
Background: * Individuals may be prone to develop blood or lymph node cancers (leukemia or lymphoma) for a variety of reasons, including genetic predisposition to these cancers, environmental exposures or other medical conditions. * Studies of people and families at high risk of cancer often lead to clues about their cause that may also be important regarding the sporadic occurrence of these cancers in the general population. * Identifying genetic or environmental factors that play a role in the development of these diseases may be important in developing prevention trials, screening programs and treatments. Objectives: * Describe the cancers and other conditions in families with blood or lymph node cancer. * Find and describe genes that may cause blood and lymph node cancer, and understand how they work in families. * Use laboratory methods to try to determine if it is possible to identify who is at highest risk of blood or lymph node cancer. * Test how genes act with other factors to alter the risk of disease, its severity or its manifestations in families. Eligibility: * Individuals of any age with a personal or family history of a blood or lymph node cancer. * Individuals with a personal or family history of medical conditions or environmental exposures that may predispose to blood or lymph node cancer. Design: * Participants complete questionnaires about their personal and family medical history and provide consent for researchers to review their medical records and pathology materials related to their care and those of deceased relatives with blood or lymph node cancer, tumors, or other related illnesses for whom they are the legally authorized representative. * Participants donate a sample of blood or cheek cells, or a lock of hair for genetic studies. * Patients may also be evaluated at the NIH Clinical Center by one or more of the following specialists: cancer doctor or blood specialist, medical geneticist, research nurses or clinical social worker. They may have blood and urine tests and a cheek swab or mouth wash to collect cheek cells. Some patients may also be asked to have x-rays and routine imaging, such as CT scans or ultrasound tests, cell surface markers, skin biopsy, and, with special consents, bone marrow biopsy, MRI or PET scans, apheresis or fluorescein angiography and photography.
This is a phase I, open-label, dose-escalation study to determine the MTD of selumetinib when combined with the standard dose of azacitidine. Treatment will begin within 28 days of screening procedures. Treatment will continue indefinitely, provided that the patient continues to derive benefit. A patient will be taken off study for reasons described in detail in section 3.12 including disease progression, unacceptable toxicity, inter-current illness, withdrawal of consent, or at the discretion of the investigator. Patients will be followed for 12 weeks after the last dose of study drug, until any study treatment related toxicities have stabilized, or until death. The total duration of the study is expected to be approximately 24 months.