Blood and Lymph Conditions

All Conditions

Rare Diseases

Lymphohistiocytosis, Hemophagocytic

Histiocytosis

Histiocytosis, Non-Langerhans-Cell

Lymphatic Diseases

Non-Langerhans-Cell Histiocytosis

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Interferons

Interferon-gamma

Patients were administered Emapalumab-Lzsg by intravenous (i.v.) infusion over a period of 1 to 2 hours, at an initial dose of 6 mg/kg and continued at 3 mg/kg, every 3 days for the first 2 weeks (Study Day \[SD\] 15), and then twice-a-week. If the treating physician deemed appropriate, the dose of emapalumab could be increased (up to 10 mg/kg), guided by clinical and laboratory response.

Emapalumab-Lzsg

Radmila Kanceva

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening condition characterized by uncontrolled hyperinflammation which may develop on the background of several clinical conditions (e.g. autoimmune disease, infection, malignancy). Emapalumab (previously referred to as NI-0501) is a monoclonal antibody neutralizing interferon-gamma (IFN-gamma), a key cytokine driving the inflammation and tissue damage seen in HLH. The purpose of this study is to assess the efficacy, safety and pharmacokinetics of emapalumab in adult patients with secondary HLH.

Study NI-0501-10 is an open-label, single arm, multicenter, Phase 2/3 interventional study.

The study enrolls adult patients with hemophagocytic lymphohistiocytosis (HLH), specifically newly diagnosed patients with malignancy-associated HLH (M-HLH), and newly diagnosed or previously treated patients with non-malignancy-associated HLH.

A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Emapalumab in Adult Patients With HLH

A Phase 2/3, Open-label, Single Arm, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Emapalumab in Adult Patients With Hemophagocytic Lymphohistiocytosis

Achievement of either a Complete or Partial Response

Complete Response is adjudicated if the following are observed:

* No fever = body temperature \<37.5°C
* Normal spleen size
* No cytopenia = Absolute Neutrophil Counts \>=1.0x10\^9/L and platelet count \>=100x10\^9/L \[absence of G-CSF and transfusion support must be documented for at least 4 days to report no cytopenia\]
* No hyperferritinemia = serum level is \<2000 µg/L
* No evidence of coagulopathy, i.e., normal D-Dimer and/or normal (\>150 mg/dL) fibrinogen levels
* No neurological and CSF abnormalities attributed to HLH
* No sustained worsening of sCD25 (as indicated by at least two consecutive measurements that are \>2-fold higher than baseline)

Partial Response is adjudicated if there is an improvement (\>50% change from baseline or normalization) of at least 3 HLH clinical and laboratory criteria (including Central Nervous System abnormalities).

As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.

Levels of interferon-gamma, C-X-C chemokine ligand 9, soluble CD25, interleukin-6.

Light Chain Bioscience - Novimmune SA

Swedish Orphan Biovitrum

The All Treated analysis set included all patients who received at least 1 dose or 1 incomplete dose of emapalumab. Only TEAEs are reported.

Patients were administered emapalumab 6 mg/kg IV infusion for 1 to 2 hours, and continued at 3 mg/kg every 3 days for the first 2 weeks, and then twice-a-week until clinically satisfactory response was achieved.

If the treating physician deemed appropriate, the dose of emapalumab could be increased (up to 10 mg/kg), guided by clinical and laboratory response.

Emapalumab

Age, Continuous

>= 18 and 64 years

>= 65 and 84 years

>= 85 years

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race

Race/Ethnicity, Customized

United States

Region of Enrollment

Weight

Height

The All Treated analysis set included all patients who received at least 1 dose or 1 incomplete dose of emapalumab.

Since the study was prematurely terminated, and considering the low number of patients enrolled, no analysis related to primary and secondary efficacy endpoints and no Pharmacokinetic and Pharmacodynamic summary statistics were performed. Accordingly, no conclusion on the efficacy of emapalumab on this patient population could be withdrawn from the study.

Radmila Kanceva, MD

Since the study was prematurely terminated, no data was collected for the primary efficacy endpoint.

Overall Response

Since the study was prematurely terminated, no data was collected for the secondary efficacy endpoints.

Best Response on Treatment

Overall Survival

Time to Complete Response or Partial Response

Duration of Response

Hemophagocytic Lymphohistiocytosis Relapse

Since the study was prematurely terminated, no data was collected for the secondary safety endpoints.

Incidence, Severity, Causality and Outcomes of Serious Adverse Events and Non-serious Adverse Events

Since the study was prematurely terminated, no data was collected for the secondary Pharmacokinetic endpoints.

Serum Concentrations of Emapalumab

Since the study was prematurely terminated, no data was collected for the secondary Pharmacodynamic endpoints.

Serum Biomarker Levels

Incidence of Anti-Drug Antibodies Against Emapalumab

Patients were administered emapalumab 6 milligram per kilogram (mg/kg) intravenous (IV) infusion for 1 to 2 hours, and continued at 3 mg/kg every 3 days for the first 2 weeks, and then twice-a-week until clinically satisfactory response was achieved.

If the treating physician deemed appropriate, the dose of emapalumab could be increased (up to 10 mg/kg), guided by clinical and laboratory response.

Overall Study

Infections

Neoplasms

Immune System Diseases

Symptoms and General Pathology

Lymphoma

Communicable Diseases

Epstein-Barr Virus Infections

Lymphoproliferative Disorders

Hodgkin Disease

Virus Diseases

Viremia

Infectious Mononucleosis

Neoplasms by Histologic Type

Immunoproliferative Disorders

Herpesviridae Infections

DNA Virus Infections

Tumor Virus Infections

Sepsis

Toxemia

Syndrome

Systemic Inflammatory Response Syndrome

Inflammation

Lymphosarcoma

Hodgkin Lymphoma

Post-transplant Lymphoproliferative Disease

Primarily transplant recipients undergoing monitoring for EBV and patients suspected for having PTLD.

Patients diagnosed with PTLD and other kinds of lymphoma. Patients undergoing hematopoietic stem cell transplantation and patients with hemophagocytosis.

Children undergoing transplantation. Children diagnosed with hemophagocytic lymphohistiocytosis.

Lene Ugilt, MD

Epstein-Barr virus (EBV) is one of several herpesviruses that cause disease in humans. EBV virus has an oncogenic potential, and it has been associated with the development of a wide range of cancers. Previous studies have shown a close association between EBV and Post-Transplant Lymphoproliferative disorder (PTLD) in transplant recipients. As part of a preventive approach against PTLD, several transplantation units now monitor the occurrence of EBV-DNAemia after transplantation. However, there is little evidence to guide this strategy; nor is there consensus concerning either the best specimen to use for EBV analysis (whole blood or plasma).

In this study investigators aim to optimise and validate a polymerase chain reaction (PCR)-test for EBV-DNA on, respectively, whole blood, plasma and a combination of plasma and lymphocytes.

The investigators wish to determine which of the three tests best predicts current and future risk of development of EBV-related diseases such as mononucleosis and PTLD.

EBV is one of several herpesviruses that cause disease in humans. Primary EBV infection usually occurs in early childhood and is generally asymptomatic, while later infection may cause mononucleosis. As with other herpesviruses, primary infection is followed by persistent (lifelong) infection. EBV virus has an oncogenic potential, and it has been associated with the development of a wide range of cancers. Previous studies have shown a close association between EBV and PTLD in transplant recipients. As part of a preventive approach against PTLD, several transplantation units now monitor the occurrence of EBV-DNAemia after transplantation. However, there is little evidence to guide this strategy; nor is there consensus concerning either the best specimen to use for EBV analysis (whole blood or plasma) or the appropriate clinical action to take if EBV-DNAemia is detected.

In this study investigators aim to optimise and validate a polymerase chain reaction (PCR)-test for EBV-DNA on, respectively, whole blood and a combination of plasma and lymphocytes.

Results obtained with the two new methods will be compared with those from the already established World Health Organization (WHO) standardised EBV-PCR test on ethylenediaminetetraacetic acid (EDTA)-plasma. The result of all three tests will be evaluated relative to EBV-related symptoms and other diseases.

The investigators wish to determine which of the three tests best predicts current and future risk of development of EBV-related diseases such as mononucleosis and PTLD.

Early Detection of Epstein-Barr Virus Related Disease.

Early Detection of Epstein-Barr Virus Related Disease. Improving Quantification of EBV in Blood Samples Using Polymerase Chain Reaction.

Symptoms compatible with EBV disease combined with a tissue biopsy positive for EBV

Symptoms compatible with EBV disease combined with a positive EBV-PCR

Aarhus University Hospital

University of Aarhus

Hematologic Neoplasms

Hematologic Diseases

Adult patients with hematologic malignancies that have sCD25\>3,900 U/mL and ferritin \>1,000 ng/mL

Adult patients with hematologic malignancies, with sCD25\>3,900 U/mL and/or ferritin \< 1,000 ng/mL

Adi Zoref Lorenz, MD

Uri Abadi, MD

Ronit Gurion, MD

Adi Zoref-Lorenz

Hemophagocytic lymphohistiocytosis (HLH) associated with hematologic malignancies (HM-HLH) is a syndrome with an abysmal prognosis (10-30% 5 years overall survival). We have recently established an improved diagnostic and prognostic index for HM-HLH, termed the Optimized HLH Inflammatory (OHI) index. The OHI index is comprised of the combined elevation of soluble CD25 (sCD25) \> 3,900 U/mL and ferritin \>1,000 ng/mL . However, the true incidence and outcomes of HLH/OHI+ in an unselected cohort are unknown and so is the mechanism of HM-HLH.

The investigators will enroll patients with new/transformed hematologic malignancies. We will follow the patients until the end of the study, report their survival at one year and examine their prognosis.

Serum samples and peripheral blood mononuclear cells

Prospective Validation of the OHI Index

A Prospective Study to Validate the Prognostic Power of the Optimized HLH Inflammatory (OHI) Index

We will use Kaplan-Meier curves to compare survival between OHI+ and OHI- patients

We will assess the incidence of OHI+ within our cohort (OHI+/total patients enrolled)

Children's Hospital Medical Center, Cincinnati

Rabin Medical Center

Sheba Medical Center

Schneider Children's Medical Center, Israel

Meir Medical Center

Gaurav Goyal, MD

The purpose of the study is to describe Hemophagocytic lymphohistiocytosis (HLH) in patients with lymphoma to identify possible therapeutic strategies to improve overall survival of the patients with lymphoma associated hemophagocytic lymphohistiocytosis.

Retrospective, multi-institutional study focused on describing the clinical features, laboratory parameters, treatments, and outcomes among individuals presenting with HLH in the setting of a lymphoma

Describing Treatment Outcomes and Responses in Lymphoma-associated Hemophagocytic Lymphohistiocytosis

The investigators will gather data on different treatments received, time to treatment, and other factors and determine which is associated with survival.

University of Alabama at Birmingham

Principal Investigator

Hypersensitivity

Patients with histopathologically confirmed lymphoma who did not receive systemic chemotherapy before enrollment.

Patients with histopathologically confirmed lymphoma who meet HLH-04 diagnostic criteria, and did not receive systemic chemotherapy before enrollment.

Peripheral blood samples were collected at diagnosis, 2 weeks after the first cycle of chemotherapy and 2 weeks after the second cycle of chemotherapy to monitor cytokine level changes.

cytokine

Zhao Wang

Zhao Wang, MD

Lymphoma-associated hemophagocytic lympohistiocytosis is a refractory immune disorder with high mortality. Early identification and diagnosis of lymphoma-associated HLH has become the key to improve the prognosis of lymphoma-associated HLH. Therefore, we conduct a multicenter, prospective, observational clinical study to explore the sensitivity and specificity of cytokines for the early diagnosis of lymphoma-associated HLH.

Lymphoma-associated hemophagocytic lympohistiocytosis is a refractory immune disorder with high mortality. Without early intervention, the median survival time is less than 2 months. Early identification and diagnosis of lymphoma-associated HLH has become the key to improve the prognosis of lymphoma-associated HLH. Therefore, it is urgent to find a method for the early diagnosis of lymphoma-associated HLH. We conduct a multicenter, prospective, observational clinical study to explore the sensitivity and specificity of cytokines for the early diagnosis of lymphoma-associated HLH, and its correlation with disease severity, treatment response, and prognosis.

Sensitivity and Specificity of Cytokines in the Diagnosis of Lymphoma-associated HLH

The Role of Cytokines in Early Diagnosis, Assessment of Response and Prognosis of Patients With Lymphoma-associated Hemophagocytic Lymphohistiocytosis

The sensitivity and specificity of cytokines as a means of early diagnosis of lymphoma-associated hemophagocytic lymphohistiocytosis

To monitor the correlation between cytokine levels and disease severity, treatment response and prognosis of lymphoma-associated hemophagocytic lymphohistiocytosis

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Emapalumab in Adult Patients With HLH	NCT03985423	Hemophagocytic ...	Emapalumab-Lzsg	18 Years -	Swedish Orphan Biovitrum
Early Detection of Epstein-Barr Virus Related Disease.	NCT03546101	Post-transplant... Mononucleosis Epstein-Barr Vi... Epstein-Barr Vi... Epstein-Barr Vi... Epstein-Barr Vi... Epstein-Barr Vi... Hemophagocytic ... Hemophagocytosi...		-	University of Aarhus
Prospective Validation of the OHI Index	NCT05882175	HLH Hemophagocytic ... Hemophagocytic ... Hematologic Mal... Hematologic Neo...		18 Years -	Meir Medical Center
Early Detection of Epstein-Barr Virus Related Disease.	NCT03546101	Post-transplant... Mononucleosis Epstein-Barr Vi... Epstein-Barr Vi... Epstein-Barr Vi... Epstein-Barr Vi... Epstein-Barr Vi... Hemophagocytic ... Hemophagocytosi...		-	University of Aarhus
Describing Treatment Outcomes and Responses in Lymphoma-associated Hemophagocytic Lymphohistiocytosis	NCT05898477	Lymphoma Hemophagocytic ...		-	University of Alabama at Birmingham
Sensitivity and Specificity of Cytokines in the Diagnosis of Lymphoma-associated HLH	NCT05600959	Hemophagocytic ... Lymphoma	cytokine	18 Years - 65 Years	Beijing Friendship Hospital
Prospective Validation of the OHI Index	NCT05882175	HLH Hemophagocytic ... Hemophagocytic ... Hematologic Mal... Hematologic Neo...		18 Years -	Meir Medical Center
A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Emapalumab in Adult Patients With HLH	NCT03985423	Hemophagocytic ...	Emapalumab-Lzsg	18 Years -	Swedish Orphan Biovitrum
Sensitivity and Specificity of Cytokines in the Diagnosis of Lymphoma-associated HLH	NCT05600959	Hemophagocytic ... Lymphoma	cytokine	18 Years - 65 Years	Beijing Friendship Hospital
Early Detection of Epstein-Barr Virus Related Disease.	NCT03546101	Post-transplant... Mononucleosis Epstein-Barr Vi... Epstein-Barr Vi... Epstein-Barr Vi... Epstein-Barr Vi... Epstein-Barr Vi... Hemophagocytic ... Hemophagocytosi...		-	University of Aarhus

Spots Global Cancer Trial Database for hemophagocytic lymphohistiocytoses