A Study of PRT543 in Participants With Advanced Solid Tumors and Hematologic Malignancies
Relapsed/Refractory Advanced Solid TumorsRelapsed/Refractory Diffuse Large B-cell Lymphoma6 moreThis is a Phase 1 cohort, dose-escalation, dose-expansion study of PRT543 in patients with advanced cancers who have exhausted available treatment options. The purpose of this study is to define a safe dose and schedule to be used in subsequent development of PRT543.
Compassionate Use Study of Tenalisib (RP6530)
Hematological MalignanciesTenalisib has been evaluated as an investigational new drug in number of early clinical studies in patients with relapsed/refractory hematological malignancies and demonstrated acceptable safety and promising efficacy in these patients. Since these advanced relapsed/refractory patients have limited therapeutic options, it is reasonable to continue Tenalisib in responding patients post completion of their participation in previous clinical studies.
PROACTIVE: Preventing Acute/Chronic GVHD With TocIlizumab Combined With GVHD Prophylaxis Post allogEneic...
Hematologic MalignancyThis is a phase II open-label trial designed to evaluate the efficacy of tocilizumab in improving GVHD-free/relapse-free survival (GRFS) after allogeneic hematopoietic cell transplantation (alloHCT) for hematologic malignancy.
PDR001 Plus LAG525 for Patients With Advanced Solid and Hematologic Malignancies
Small Cell Lung CancerGastric Adenocarcinoma6 moreThe purpose of this signal seeking study is to determine whether treatment with PDR001 and LAG525 demonstrates sufficient efficacy in advanced malignancies to warrant further study.
Phase I Trial of BAY1251152 for Advanced Blood Cancers
Hematologic NeoplasmsThe purpose of this study is to identify the most appropriate dose that can be safely administered and that can have an effect on blood cancer cells. Once that safe dose is identified, additional patients will be asked to join the study to further evaluate the safety and effectiveness of the study drug. The study will also investigate the pharmacokinetics (study of what the body does to the drug), as well as pharmacodynamics (study of what the drug does to the body), which may provide information about the effects of BAY 1251152. The study will also measure some biological markers (markers of biological activity in your body) that can be used to predict the response and safety of the proposed treatment.
MiHA-loaded PD-L-silenced DC Vaccination After Allogeneic SCT
Hematological MalignanciesAllogeneic stem cell transplantation (allo-SCT) is a potent treatment, and sometimes the only curative treatment for aggressive hematological malignancies. The therapeutic efficacy is attributed to the graft-versus-tumor (GVT) response, during which donor-derived CD8+ T cells become activated by recipient minor histocompatibility antigens (MiHA) presented on dendritic cells (DC). Consequently, these alloreactive donor T cells clonally expand, acquire effector functions and kill MiHA-positive malignant cells. However, in a substantial number of patients persistence and recurrence of malignant disease is observed, indicating that insufficient GVT immunity is induced. This is reflected by our observation that not all patients develop a productive CD8+ T cell response towards MiHA mismatched between the recipient and donor. We found that the PD-1/PD-L1 co-inhibitory pathway is involved in dampening MiHA-specific CD8+ T cell expansion and function post-transplantation. Therefore, a promising strategy to induce or boost GVT immune responses is pre-emptive or therapeutic vaccination with ex vivo-generated donor DCs loaded with MiHA that are exclusively expressed by recipient hematopoietic cells and their malignant counterparts. In contrast to pre-emptive donor lymphocyte infusion (DLI) with polyclonal donor T cells, this MiHA-DC vaccination approach has less risk of inducing graft-versus-host disease (GVHD) and the potency to induce more efficient GVT-associated T cell immunity. In addition, the potency of this DC vaccine will be further enhanced by interference with the PD-1/PD-L1 co-inhibitory pathway, using siRNA mediated PD-L1/PD-L2 silencing.
Evaluation of Fostamatinib in Patients With cGVHD After Allogeneic Stem Cell Transplant
Hematological MalignanciesThe purpose of this study is to evaluate whether fostamatinib, a drug that blocks activated B cells will be effective in preventing and treating chronic graft vs host disease (cGVHD) after allogeneic stem cell transplant. Activated B cells may play a role in development of cGVHD. Inhibiting the B cell activation using fostamatinib after allogeneic stem cell transplant may prevent the development of cGVHD.
Stem Cell Transplantation From HLA Partially-Matched Related Donors for Patients With Hematologic...
Acute Lymphoblastic LeukemiaAcute Myelogenous Leukemia4 moreThis clinical pilot trial is intended to evaluate the feasibility, efficacy and safety of hematopoietic stem cell transplantation (HSCT) from Human Leukocyte Antigen (HLA)-mismatched related donors for children and young adults with hematologic malignancies who lack a suitably matched related or unrelated donor. The methodology will be one that has been successfully utilized in adult patients at Thomas Jefferson University.
Myeloablative Haploidentical BMT With Post-transplant Cyclophosphamide for Pediatric Patients With...
Myeloablative ConditioningHLA-mismatched Bone Marrow Transplantation3 moreThis is a multi-institutional phase II haploidentical T cell replete bone marrow transplant (BMT) study in children with high-risk leukemia. The myeloablative conditioning regimen prescribed will be Total body irradiation (TBI)-based for lymphoid leukemia and busulfan-based for myeloid leukemia. Our goal is to establish an easily exportable, inexpensive platform for haplotransplantation that has a safety profile equivalent to matched related and unrelated BMTs. The primary objective will be to estimate the incidence of 6-month non-relapse mortality (NRM), hypothesizing that NRM is < 18%.
Haploidentical Donor Hematopoietic Progenitor Cell and NK Cell Transplantation for Hematologic Malignancy...
LeukemiaLymphomaIn this study, participants with high-risk hematologic malignancies undergoing hematopoietic cell transplantation (HCT), who do not have a suitable human leukocyte antigen (HLA) matched related/sibling donor (MSD) or matched unrelated donor (MUD) identified, will receive a haploidentical donor HCT with additional natural killer (NK) cells. The investigators anticipate enrollment of 75 donors and 75 recipients. PRIMARY OBJECTIVE: To estimate the rate of successful engraftment at day +42 post-transplant in patients who receive haploidentical donor stem cell plus NK cell transplantation with TLI based conditioning regimen for high risk hematologic malignancy. SECONDARY OBJECTIVES: Estimate the incidence of malignant relapse, event-free survival, and overall survival at one-year post-transplantation. Estimate incidence and severity of acute and chronic (GVHD). Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.