Clinical Research Directory

Comparison of Two Etoposide Initiation Strategies for Severe Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is an immune-mediated disorder characterized by hyperactivation of the immune system, leading to a cytokine storm responsible for organ failures. Consequently, patients with HLH often require intensive care management, where their short-term prognosis is compromised (1-month mortality: 30 to 40%). Therapeutic management is urgent and consists in treating associated pathologies and employing immunomodulatory therapy. Currently, there are no clear and consistent recommendations for guiding immunomodulatory treatment in HLH due to the lack of high-level evidence studies. Experts recommend corticosteroid therapy for mild forms, whereas etoposide is proposed for severe cases, especially those with organ failures. However, in clinical practice, its use in patients with multi-organ failure is not systematic due to concerns about potential severe side effects and uncertainty regarding the contribution of severe sepsis to the clinical and biological presentation. Consequently, initiation of etoposide is sometimes delayed. Our hypothesis is that early treatment of severe HLH associated with organ failure using etoposide could reduce organ failures associated with this syndrome. Therefore, we aim to compare two strategies for initiating etoposide in severe HLH in intensive care: an early strategy where etoposide is prescribed at the onset of HLH-related organ failure, and a delayed strategy where etoposide is prescribed only if there is unfavorable progression (or lack of improvement) after treating associated pathologies, associated with corticosteroid therapy.

Immune Disorder HSCT Protocol

This study hypothesizes that a reduced intensity immunosuppressive preparative regimen will establish engraftment of donor hematopoietic cells with acceptable early and delayed toxicity in patients with immune function disorders. A regimen that maximizes host immune suppression is expected to reduce graft rejection and optimize donor cell engraftment.

Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies

This is a standard of care treatment guideline for allogeneic hematopoetic stem cell transplant (HSCT) in patients with primary immune deficiencies.

Use Of A Response-Adapted Ruxolitinib-Containing Regimen For The Treatment Of Hemophagocytic Lymphohistiocytosis

This study is a multi-site Phase Ib/II, 2-arm non-randomized clinical trial to determine the efficacy and tolerability of a response-adapted regimen combining ruxolitinib, dexamethasone, and etoposide as Frontline therapy for patients with newly diagnosed hemophagocytic lymphohistiocytosis (HLH) or as Salvage therapy for patients with relapsed/refractory HLH. Primary Objective * To determine the efficacy and tolerability of a response-adapted ruxolitinib-containing regimen for patients with newly diagnosed HLH. Secondary Objectives * To describe the efficacy and tolerability of a response-adapted ruxolitinib-containing regimen for patients with relapsed/refractory HLH. * To describe the overall response and outcome for patients with newly diagnosed or relapsed/refractory HLH who are treated with this response-adapted ruxolitinib-containing regimen. Exploratory Objectives * To estimate the pharmacokinetic (PK) parameters of ruxolitinib, assess covariates of ruxolitinib pharmacokinetics, and test whether the drug's effectiveness is correlated with systemic drug exposure. * To query specific immunologic biomarkers and determine whether the levels of these biomarkers correlate with disease response and outcome.

Zanubrutinib Combined With Rituximab in the Treatment of Secondary HLH in B-cell Lymphoma

For patients who met the inclusion criteria, treatment regimens were administered: Rituximab 375 mg/m², intravenously, once weekly for 4 weeks. Zanubrutinib 160 mg, orally, twice daily for 4 weeks. Combined drugs: prednisone 100 mg/m²/d, orally, d1-5; Ruxolitinib 15mg bid orally; With/without emapalumab as appropriate.

Administration of Donor T Cells With the Caspase-9 Suicide Gene

Patients will be receiving a stem cell transplant as treatment for their disease. As part of the stem cell transplant, patients will be given very strong doses of chemotherapy, which will kill all their existing stem cells. A close relative of the patient will be identified, whose stem cells are not a perfect match for the patient's, but can be used. This type of transplant is called "allogeneic", meaning that the cells are from a donor. With this type of donor who is not a perfect match, there is typically an increased risk of developing GvHD, and a longer delay in the recovery of the immune system. GvHD is a serious and sometimes fatal side-effect of stem cell transplant. GvHD occurs when the new donor cells (graft) recognize that the body tissues of the patient (host) are different from those of the donor. In this study, investigators are trying to see whether they can make special T cells in the laboratory that can be given to the patient to help their immune system recover faster. As a safety measure, we want to "program" the T cells so that if, after they have been given to the patient, they start to cause GvHD, we can destroy them ("suicide gene"). Investigators will obtain T cells from a donor, culture them in the laboratory, and then introduce the "suicide gene" which makes the cells sensitive to a specific drug called AP1903. If the specially modified T cells begin to cause GvHD, the investigators can kill the cells by administering AP1903 to the patient. We have had encouraging results in a previous study regarding the effective elimination of T cells causing GvHD, while sparing a sufficient number of T cells to fight infection and potentially cancer. More specifically, T cells made to carry a gene called iCasp9 can be killed when they encounter the drug AP1903. To get the iCasp9 gene into T cells, we insert it using a virus called a retrovirus that has been made for this study. The AP1903 that will be used to "activate" the iCasp9 is an experimental drug that has been tested in a study in normal donors with no bad side-effects. We hope we can use this drug to kill the T cells. The major purpose of this study is to find a safe and effective dose of "iCasp9" T cells that can be given to patients who receive an allogeneic stem cell transplant. Another important purpose of this study is to find out whether these special T cells can help the patient's immune system recover faster after the transplant than they would have otherwise.

Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

CoRDS, or the Coordination of Rare Diseases at Sanford, is based at Sanford Research in Sioux Falls, South Dakota. It provides researchers with a centralized, international patient registry for all rare diseases. This program allows patients and researchers to connect as easily as possible to help advance treatments and cures for rare diseases. The CoRDS team works with patient advocacy groups, individuals and researchers to help in the advancement of research in over 7,000 rare diseases. The registry is free for patients to enroll and researchers to access. Visit sanfordresearch.org/CoRDS to enroll.

Segmental Resection Combined With DEP Regimen for EBV-HLH Patients With Intestinal Involvement

EBV-HLH is a rare disease with high mortality, especially for those with intestinal involvement. In order to reduce disease burden and improve survival of these patients, we conduct a prospective observational study to explore the efficacy and safety of segmental resection combined with the DEP regimen.

L-DEP Regimen Combined With PD-1 Antibody as Induction Therapy for Epstein-Barr Virus-positive LA-HLH

The efficacy and safety of L-DEP (PEG-aspargase, liposomal doxorubicin, etoposide, and methylprednisolone) regimen combined with PD-1 Antibody an induction therapy for Epstein-Barr virus (EBV)-positive lymphoma-associated hemophagocytic lymphohistiocytosis.

L-DEP/DEP Regimen and PD-1 Antibody as a Treatment for Relapse/Refractory EBV-HLH

This study aimed to investigate the efficacy and safety of L-DEP (L-Asparaginasum, liposomal doxorubicin, etoposide and methylprednisolone) together with PD-1 antibody as an treatment for relapse/refractory EBV associated hemophagocytic lymphohistiocytosis.