Clinical Research Directory

CD123-Directed T-Cell Therapy for Acute Myelogenous Leukemia (CATCHAML)

The CD123-CAR T-cell therapy is a new treatment that is being investigated for treatment of AML/myelodysplastic syndrome (MDS), T- or B- acute lymphoblastic leukemia (ALL) or blastic plasmacytoid dendritic cell neoplasia (BPDCN). The purpose of this study is to find the maximum (highest) dose of CD123-CAR T cells that is safe to give to these patients. This would include studying the side effects of the chemotherapy, as well as the CD123-CAR T-cell product on the recipient's body, disease and overall survival. Primary Objective: * To determine the safety of one intravenous infusion of escalating doses of autologous, CD123-CAR T cells in patients (≤21 years) with recurrent/refractory CD123+ disease (AML/MDS, B-ALL, T-ALL or BPDCN) after lymphodepleting chemotherapy. * To determine the safety of an intravenous infusion of escalating doses of donor derived, CD123-CAR T cells in patients (≤21 years) with recurrent/refractory CD123+ disease (AML/MDS, B-ALL, T-ALL, BPDCN or MPAL) after lymphodepleting chemotherapy. Secondary Objectives \- To evaluate the antileukemia activity of CD123-CAR T cells. Exploratory Objectives * To assess the immunophenotype, clonal structure and endogenous repertoire of CD123-CAR T cells and unmodified T cells * To characterize the cytokine profile in the peripheral blood and CSF after treatment with CD123-CAR T cells * To characterize tumor cells post CD123-CAR T-cell therapy * To compare in vivo properties of donor-derived versus autologous CD123- CAR T cells

SENTI-202: Off-the-shelf Logic Gated CAR NK Cell Therapy in Adults With CD33 and/or FLT3 Blood Cancers Including AML/MDS

This is an open-label study of the safety, biodynamics, and anti-cancer activity of SENTI-202 (an off-the-shelf logic gated CAR NK cell therapy) in patients with CD33 and/or FLT3 expressing blood cancers, including AML and MDS.

Danvatirsen Monotherapy Followed by Combination With Venetoclax in Relapsed/Refractory MDS & AML

This is a Phase 1 study investigating the safety and efficacy of Danvatirsen as a monotherapy followed by combination with Venetoclax in patients with relapsed/refractory myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). Funding Source: FDA OOPD

Tolerability and Efficacy of Midostaurin to 10-day Decitabine in Unfit Adult AML and High Risk MDS Patients

The aim of this study is to investigate how safe and effective the addition of the new medicine midostaurin to decitabine is for the treatment of unfit acute myeloid leukemia (AML) and high-risk myelodysplasia (MDS) patients. Patients who are ineligible for intensive chemotherapy because of accompanying diseases may opt for gentler treatment. This does not produce a cure but serves to allow the quality of life to be acceptable for as long as possible. Decitabine is an example of a gentler treatment. It is effective against leukemia and has fewer side effects than intensive chemotherapy. Given in courses of 5 successive days, decitabine is registered for the treatment of AML. There is scientific research to suggest that decitabine is more effective and generally well tolerated when given in courses of 10 successive days. Therefore, treatment with 10-day courses of decitabine is the standard treatment in this scientific research. The aim is to investigate whether this standard treatment can be improved by adding a new product, midostaurin. Midostaurin is a medicine that is directed against a specific protein on leukaemia cells (FLT3).

Innate Donor Effector Allogeneic Lymphocyte Infusion After Stem Cell Transplantation: the IDEAL Trial

The curative principle behind allogeneic hematopoietic stem cell transplantation (HSCT) is eradication of the malignant cells of the patient (recipient) by donor graft cells, a process termed graft-versus-leukemia (GVL) effect. GVL is traditionally mediated by donor αβ T cells in an immunological process driven by genetical differences between individuals, i.e. an allogeneic response. For this reason, αβ T cells also cause an unwanted and dangerous complication of HSCT called graft-versus-host disease (GVHD) in which healthy recipient cells are targeted by donor cells with great risk of morbidity and mortality to the patient. In addition to αβ T cells, other cells from the donor stem cell graft, termed innate effector lymphocytes, can contribute to the GVL effect. These are termed natural killer (NK) cells and T-cell receptor (TCR) γδ cells, the latter being a subset of T cells. NK and TCR γδ cells can recognize and eliminate leukemic cells in a direct tumor response independent of conventional allogeneicity. Therefore, opposite αβ T cells, innate effector lymphocytes cells can mediate GVL but are not likely to cause GVHD. The main indications for HSCT in adults are acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Approximately 50% of AML/MDS transplant patients experience significant acute GVHD and 30% experience relapse of the malignant disease. Prospective clinical studies from the research group of the investigators have shown that patients with high doses of innate lymphocytes in stem cell grafts and during early immune reconstitution after HSCT have a reduced risk of both GVHD and relapse. The aim of this clinical trial is therefore to administer innate donor lymphocyte infusion (iDLI) enriched in NK and TCR γδ cells and depleted of αβ T cells in patients early after HSCT. By improving the HSCT procedure with iDLI cell therapy the scope is less GVHD and less relapse of the malignant disease and thereby improved survival and life quality in AML/MDS patients.