View clinical trials related to Leukemia, Myeloid.
Filter by:This study will take place in parts: - Dose Escalation (Part 1): Participants receive milademetan alone with different dose schedules - Dose Escalation (Part 1A): Participants receive milademetan in combination with 5-azacytidine (AZA), with different dose schedules The recommended dose for Part 2 will be selected. - Dose Expansion (Part 2): After Part 1A, participants will receive the recommended Part 2 dose schedule. There will be three groups - those with: 1. refractory or relapsed acute myelogenous leukemia (AML) 2. newly diagnosed AML unfit for intensive chemotherapy 3. high-risk myelodysplastic syndrome (MDS) - End-of-Study Follow-Up: Safety information will be collected until 30 days after the last treatment. This is the end of the study. The recommended dose for the next study will be selected.
The goal of this clinical research study is to learn if ixazomib can prevent AML or MDS from coming back in patients who are in remission. The safety of this drug will also be studied.
The main trial is a double-blinded, placebo-controlled, randomized, phase III, multi-center trial in adult patients with relapsed or refractory AML harboring an activating FLT3 mutation as defined in the inclusion /exclusion criteria. An initial open label dose-finding run-in phase I of the study will be performed administering the study drug crenolanib with salvage chemotherapy consisting of mitoxantrone and cytarabine (MC) in 18 patients according to the experimental arm of the study. After completion of this dose-finding run-in phase I, toxicity and response data will be provided to the external Data and Safety Monitoring Board (DSMB) and the Trial Committee by the Coordinating Investigator. The Trial Committee will decide on the basis of these data and the recommendation of the DSMB on dose modification and the further conduct of the study with regard to the double-blinded, placebo-controlled, randomized phase of the study. The double-blinded, placebo-controlled randomized portion will start after the completion of the dose-finding run-in phase I and positive opinion of the Trial Committee. Crenolanib starts on day 7 of MC and is given continuously until 48 hours prior to the next chemotherapy; if receiving allogeneic HCT, crenolanib is held 48 hours prior to conditioning and restarts no sooner than 30 days and not later than day 100 after transplant. Sample size randomized phase: 276 patients Primary objective: To evaluate the impact of crenolanib given in combination with salvage chemotherapy and consolidation including allogeneic hematopoietic cell transplantation and ongoing single agent maintenance therapy with crenolanib on event-free (EFS) and overall survival (OS) in adult patients with relapsed or refractory AML harboring FLT3 activating mutations.
Application of a therapeutic platelet transfusion Regimen in patients with acute myeloid leukemia in complete Remission (consolidation therapy)
This is a non-randomized open label multi-center study. Patients who are in their first complete remission (CR) following induction therapy will be treated with SL-401, which will be administered as a brief intravenous infusion for 5 consecutive days every 28 days for 6 or more cycles. Stage 1 will consist of a period in which approximately 6-9 patients will be treated with SL-401 at 3 dose levels. During Stage 2, up to approximately 20 patients with minimal residual disease (MRD) in their bone marrow will be treated at a maximum tolerated dose or maximum tested dose in which multiple dose-limiting toxicities are not observed (identified in Stage 1).
This study is being done to evaluate the safety and effectiveness of APTO-253 for the treatment of patients with the condition of acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) for which either the standard treatment has failed, is no longer effective, or can no longer be administered safely or poses a risk for your general well being.
This pilot phase II trial studies how well a new reduced intensity conditioning regimen that includes haploidentical donor NK cells followed by the infusion of selectively T-cell depleted progenitor cell grafts work in treating younger patients with hematologic malignancies that have returned after or did not respond to treatment with a prior transplant. Giving chemotherapy and natural killer cells before a donor progenitor cell transplant may help stop the growth of cells in the bone marrow, including normal blood-forming cells (progenitor cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's cells. When the healthy progenitor cells from a related donor are infused into the patient they make 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 (called graft-versus-host disease). Removing specific T cells from the donor cells before the transplant may prevent this.
This research study is evaluating the safety and tolerability of the drug lenalidomide in combination with and following mismatched related donor microtransplantation in high risk AML patients in first remission. This study also aims to define the maximum tolerated dose (MTD) of lenalidomide given in this setting. Microtransplantation seeks to give the participant donor cells in hopes that those cells can attack the underlying cancer. However, since the donor cells do not replace all of the host cells, it can hopefully avoid many of the serious risks involved with standard transplant, including graft-vs.-host disease (GVHD) - a complication where the donor cells attack the participant's normal body. Recent studies have suggested that lenalidomide can help aid donor cells to attack cancer when given after a stem cell transplant. This trial is trying to see if lenalidomide can help encourage the attack of leukemia cells by donor cells given as part of microtransplantation. The FDA (the U.S. Food and Drug Administration) has approved lenalidomide but it has been approved for other uses such as in the treatment of other cancers including multiple myeloma and non-Hodgkin lymphoma. Although lenalidomide has been studied in patients with AML, it has not been approved by the FDA for standard use in AML. Lenalidomide is a compound made by the Celgene Corporation. It has properties which could demonstrate antitumor effects. The exact antitumor mechanism of action of lenalidomide is unknown.
Allogeneic hematopoetic stem cell transplantation (SCT) is frequently complicated by life threatening viral reactivation. Conventional antiviral therapy is suboptimal for cytomegalovirus (CMV), adenovirus (AdV) and Epstein-Barr virus (EBV) and nonexistent for BK virus (BKV). An alternative approach to prevent viral reactivation is to infuse virus-specific cytotoxic T cells (CTL) prepared from the donor early after SCT. Such multivirus-specific CTL cells (MVST) have been successfully used in a number of centers to prevent or treat CMV, Ad and EBV. Activity of BKV-reactive cells has not been studied. Multi virus-specific T cells (MVST) are donor lymphocytes that are highly enriched for viral antigens and expanded in vitro before infusion into the transplant recipient. Viral reactivation is a particular problem inT cell depleted SCT. Median time to CMV reactivation is estimated as 28 days post T-depleted transplant, but infusion of MVST within the immediate post-SCT period has not been previously studied. This protocol will be the first of a planned series of cellular therapies to be layered on our existing T lymphocyte depleted transplant platform protocol 13-H-0144. The aim of this study is to determine the safety and efficacy of very early infusion of MVST directed against the four most common viruses causing complications after T-depleted SCT. GMP-grade allogeneic MVST from the stem cell donor will be generated using monocyte-derived donor dendritic cells (DCs) pulsed with overlapping peptide libraries of immunodominant antigens from CMV, EBV, Ad, and BKV and expanded in IL-7 and IL-15 followed by IL-2 for 10-14 days. A fraction of the routine donor leukapheresis for lymphocytes obtained prior to stem cell mobilization will be used to generate the MVST cells. MVST passing release criteria will be cryopreserved ready for infusion post SCT. Eligible subjects on NHLBI protocol 13-H-0144 will receive a single early infusion of MVST within 30 days (target day +14, range 0-30 days) post SCT. Phase I safety monitoring will continue for 6 weeks. Viral reactivation (CMV, EBV, Ad, BK) will be monitored by PCR by serial blood sampling. The only antiviral prophylaxis given will be acyclovir to prevent herpes simplex and varicella zoster reactivation. Subjects with rising PCR exceeding threshold for treatment, or those with clinically overt viral disease will receive conventional antiviral treatment. Patients developing acute GVHD will receive standard treatment with systemic steroids. These patients are eligible for reinfusion of MVST when steroids are tapered. The clinical trial is designed as a single institution, open label, non-randomized Phase I/II trial of MVST in transplant recipients, designed as 3-cohort dose escalation Phase I followed by a 20 subject extension Phase II at the maximum tolerated dose of cells. Safety will be monitored continuously for a period of 6 weeks post T cell transfer. The primary safety endpoint will be the occurrence of dose limiting toxicity, defined as the occurrence of Grade IV GVHD or any other SAE that is deemed to be at least probably or definitely related to the investigational product. The primary efficacy endpoint for the phase II will be the proportion of CMV reactivation requiring treatment at day 100 post transplant. Secondary endpoints are technical feasibility of MSVT manufacture, patterns of virus reactivation by PCR, and clinical disease from EBV, Ad, BK, day 100 non-relapse mortality.
The trial investigates the efficacy of adoptive immunotherapy with haploidentical natural killer cells compared to standard chemotherapy (after first complete remission) in patients with a high-risk acute myeloid leukemia being older than 65 years of age and not eligible for allogeneic transplantation