Infections

All Conditions

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Immune System Diseases

Rare Diseases

Leukemia

Communicable Diseases

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Mycoses

Invasive Fungal Infections

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

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Lymphatic Diseases

Immunoproliferative Disorders

Bacterial Infections

Bacterial Infections and Mycoses

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

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Anti-Infective Agents

All Drugs and Chemicals

Amphotericin B

Liposomal amphotericin B

Amebicides

Antiprotozoal Agents

Antiparasitic Agents

Anti-Bacterial Agents

Clotrimazole

Miconazole

Antifungal Agents

Liposomal amphotericin B 5 mg/kg twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy

Placebo to match liposomal amphotericin B twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy

Ambisome 5 mg/kg twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week during induction chemotherapy

Placebo to match liposomal amphotericin B administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy

Placebo

Mike Hawkins, MD

The study aims to investigate whether prophylaxis with liposomal amphotericin B (AmBisome®) can reduce the incidence of invasive fungal infections (IFIs) in patients with Acute Lymphoblastic Leukemia (ALL) who are undergoing their first remission induction.

Prevention of Invasive Fungal Infections (IFIs) in Subjects Receiving Chemotherapy for Acute Lymphoblastic Leukemia

A Phase 3, Double-Blind, Multicenter, Randomized, Placebo-Controlled Study to Assess the Efficacy, Safety and Tolerability of Prophylactic Liposomal Amphotericin B (AmBisome®) for the Prevention of Invasive Fungal Infections (IFIs) in Subjects Receiving Remission-Induction Chemotherapy for Acute Lymphoblastic Leukemia (ALL)

Diagnoses of proven or probable invasive fungal infections (IFI) were assessed according to European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria by the independent data review board (IDRB) who were blinded to treatment assignment.

The duration of remission-induction chemotherapy was defined as the period from the initiation of remission-induction chemotherapy administration to the start of consolidation or salvage therapy.

Time to diagnosis of proven or probable IFIs is presented as the median (Q1,Q3) days to diagnosis of those participants who experienced a proven or probable IFI. Median was not reached if \< 50% of participants had an event; Q1 was not reached if \< 25% of participants had an event; Q3 was not reached if \< 75% of participants had an event.

This endpoint was to evaluate the potential impact of IFI prevention on the efficacy of remission-induction chemotherapy for ALL.

Gilead Sciences

Safety Analysis Set; participants who were randomized and received at least 1 dose of study drug.

The duration of remission-induction chemotherapy was defined as the period from the initiation of remission-induction chemotherapy administration to the start of consolidation or salvage therapy.

Liposomal Amphotericin B

Total

Age, Continuous

≤ 25 years

> 25 to ≤ 60 years

> 60 years

Age, Customized

Sex: Female, Male

Asian

Black

White

Not Permitted

Other

Race/Ethnicity, Customized

Germany

Italy

France

Belgium

Spain

Greece

Portugal

Turkey

Austria

Israel

Switzerland

Brazil

Argentina

Region of Enrollment

Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug.

Clinical Trial Disclosures

A two-group Cochran-Mantel-Haenszel (CMH) test with a 0.05 two-sided significance level and 2:1 allocation of 354 randomized subjects (236 AmBisome, 118 placebo) would have 81% power to detect a relative reduction of 75% if the rate of IFI is 10% in the placebo group (based on unpublished data from the German Multicenter Acute Lymphoblastic Leukemia Working Group (GMALL) and consistent with the published rate of 16.4% in patients with hematological malignancies undergoing remission induction).

Intent-to-Treat (ITT) Analysis Set: participants in the safety analysis set who had no major violations of entrance criteria.

Percentage of Participants With Proven or Probable IFIs During Remission-induction Chemotherapy for Acute Lymphoblastic Leukemia (ALL)

Percentage of Participants With Pulmonary Infiltrates According to the Central Image Reader

Percentage of Participants Diagnosed With Proven or Probable IFIs According to the EORTC/MSG Criteria, as Assessed by the Investigator

Time to Diagnosis of Proven or Probable IFIs According to the EORTC/MSG Criteria, as Assessed by the IDRB.

Percentage of Participants Requiring Antifungal Treatment During Remission-Induction Chemotherapy

Percentage of Participants Who Died Due to Fungal Infection; Causality as Assessed by the IDRB.

Percentage of Participants Who Died Due to Fungal Infection; Causality as Assessed by the Investigator.

Time From Beginning of Remission-induction Chemotherapy Until the Beginning of Consolidation Therapy

Participants were not stratified for leukemia risk.

Percentage of Participants With Complete Remission at the End of Remission Induction

Liposomal amphotericin B (AmBisome®) 5 mg/kg twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy

Overall Study

Hematologic Neoplasms

Isavuconazole

Patients will receive an intravenous (IV) loading regimen of isavuconazonium sulfate, which consists of a dose every 8 hours (+/- 2 hours) on days 1 and 2, followed by once daily IV maintenance dosing for up to 26 additional days (for a maximum of 28 days of dosing).

Patients will receive an IV loading regimen of isavuconazonium sulfate, which consists of a dose every 8 hours (+/- 2 hours) on days 1 and 2, followed by once daily IV maintenance dosing for up to 26 additional days (for a maximum of 28 days of dosing).

Patients will receive a loading regimen of isavuconazonium sulfate by oral administration, comprising one dose every 8 hours (+/- 2 hours) on days 1 and 2 (a total of six doses), followed by once daily oral maintenance dosing for up to 26 additional days (for a maximum of 28 days of dosing).

isavuconazonium sulfate - intravenous

isavuconazonium sulfate - oral

Senior Medical Director

The purpose of the study is to evaluate the pharmacokinetics (PK), safety and tolerability of multiple doses of intravenous (IV) and oral isavuconazonium sulfate administered daily in pediatric patients. The PK data will be utilized to establish a pediatric population PK model of isavuconazole, the active moiety of isavuconazonium sulfate.

A Study of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients

A Phase 1, Open-label, Multicenter, Non-comparative Pharmacokinetics and Safety Study of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients

Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."

Maximum concentration at steady state (Cmax) will be derived from the PK plasma samples collected.

Area under the concentration time curve from the time of dosing to the start of next dosing interval at multiple dose conditions (AUCtau) will be derived from the PK plasma samples collected.

Time of maximum concentration (tmax) will be derived from the PK plasma samples collected.

Concentration - trough level (Ctrough) will be derived from the PK plasma samples collected.

Volume of distribution at steady state (Vss) will be model-derived.

Area under the concentration-time curve at steady state (AUCss) will be model-derived.

A TEAE is defined as an Adverse Event (AE) observed after starting administration of the study drug through follow-up. AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). Number of patients with TEAE's will be summarized.

An abnormality identified during a medical test (e.g. vital signs) should be defined as an AE only if the abnormality meets 1 of the following criteria: induces clinical signs or symptoms; requires active intervention; requires interruption or discontinuation of study drug; or the abnormality or test value is clinically significant.

An abnormality identified during a medical test (e.g. laboratory parameter) should be defined as an AE only if the abnormality meets 1 of the following criteria: induces clinical signs or symptoms; requires active intervention; requires interruption or discontinuation of study drug; or the abnormality or test value is clinically significant.

Standard 12-lead ECG recordings will be used for the purposes of safety assessment. A 12-lead, resting ECG is to be recorded. Patients should remain supine for at least 5 minutes prior to all ECGs being performed. The results (normal, abnormal not clinically significant, abnormal clinically significant) are to be recorded.

Basilea Pharmaceutica International Ltd

Astellas Pharma Global Development, Inc.

Candidiasis

Candidiasis, Invasive

Systemic Candidiasis

Anidulafungin

standard dose: 200mg/d on day 1, followed by 100mg/d from day 2 as maintenance dose.

Prophylaxis will be given until the recovery from neutropenia (ANC \> 1,0 G/L without myelosupportive medications) and in cases of active fungal infection until best response, in case of fungemia for at least 2 weeks after the first negative culture.

Michael Girschikofsky, MD

Study objectives To evaluate the safety of the echinocandin anidulafungin for prophylaxis or treatment of invasive fungal infections (IFI) in hematologic patients.

Study design, Study conduct period Prospective, open label, phase II, one arm, single centre study October 2009 - September 2010

Study population Twenty adult patients (≥ 18 years) with a hematologic disorder and an indication for antifungal prophylaxis or therapy, but a relative contraindication for azoles or polyenes due to hepatic and renal dysfunction respectively

Methods and Main Out-come Variables Main Outcome Parameter Safety: Adverse events and changes of important laboratory parameters with clinical impact will be reported.

Secondary Outcome Parameter Efficacy: In therapeutically use the outcome will be categorized into success or failure. For patients receiving anidulafungin as prophylaxis the number and rate of breakthrough infections will be documented.

Risk assessment Treatment related adverse effects as reported in the approved physician prescribing information (usually mild and with an incidence of \< 5%). Treatment failure due to resistant pathogens.

Expected benefit from this study IFI is a major cause of death among hematological patients, especially those undergoing high dose chemotherapy. It is conceivable that anidulafungin is a new treatment option for patients in whom azoles or polyenes are relatively contraindicated.

Treatment of patients with hematologic disorders is frequently complicated by invasive fungal infections (IFI). The current spectrum of pathogens in this patient population is characterised by an increasing rate of aspergillosis, atypical moulds and yeasts, which might be explained by an extended application of myelosuppressive chemotherapy and prophylactic use of antibiotic therapy, but also more sensitive diagnostic tools. Although several new antifungal drugs have been approved recently for the treatment of invasive fungal infections, the mortality rates remain unacceptably high. In patients with suspected IFI invasive diagnostic procedures can often not be performed due to thrombocytopenia and blood testing of fungal antigens with ELISA or PCR-methods are at most additive tools at this time. Thus, antifungal drugs are frequently applied empirically when neutropenic fever persists despite of antibiotic therapy or preemptive in case of radiological or laboratory suspicion of IFI. The antifungal armamentarium consists mainly of azoles, polyenes, and echinocandins. Therapy with azoles is frequently complicated by hepatological side effects and drug interactions, whereas the application of polyenes is often associated with a worsening of the renal function, severe hypopotassemia and shivering. Because of their favourable efficacy and outstanding safety profile, nowadays echinocandins are increasingly used in hematologic wards, especially in patients with renal or liver comorbidity. Anidulafungin is a novel echinocandin with potent invitro fungicidal activity against several pathogen yeasts and moulds like Candida- or Aspergillus spp. It has recently been approved by the EMEA for treatment of invasive candidiasis in non-neutropenic patients. A low cytochrome P450 interaction profile has been reported and dose adaption in case of hepatical or renal impairment is not recommended. In the pivotal clinical trial anidulafungin achieved a superior response rate for treatment of invasive candida infection in comparison with fluconazole. In this trial, only a quarter of patients had cancer and only 3% had neutrophil counts below 500/cm3 blood at randomisation. Although the clinical experience of the efficacy and tolerability of anidulafungin in adult hematologic patients is limited, the Infectious Diseases Society of America recently recommended anidulafungin for use in neutropenic patients with candidiasis.

Primary endpoint:

Safety: For all patients who will receive anidulafungin without regard to indication the incidence of (serious) adverse events and changes of important laboratory parameters (in particular liver and renal function parameters) with clinical impact will be reported.

Secondary endpoints:

Pharmacokinetics Efficacy

For patients receiving anidulafungin as prophylaxis the number and rate of breakthrough infections will be reported. If breakthrough infection occurs the type of salvage therapy and the outcome will also be documented. For patients receiving anidulafungin as treatment of a current episode of a fungal infection the primary efficacy outcome is defined as the proportion of patients alive at week six after inclusion in the study or at the time that a patient is censored. A second evaluation of survival will be done at week 12. Reason of death will be analyzed according to toxicity of study drug and progression of IFI, respectively.

The efficacy outcome will be categorized into the following:

Success:

Complete response: Survival within the prespecified period of observation, resolution of all attributable symptoms and signs of disease and radiological abnormalities, and mycological evidence of eradication of disease.

Partial response: Survival within the prespecified period of observation, improvement in attributable symptoms and signs of disease and radiological abnormalities, and evidence of clearance of cultures or reduction of fungal burden, as assessed by a quantitative and validated laboratory marker.

Failure: Stable response: Survival within the prespecified period of observation and minor or no improvement in fungal disease, but no evidence of progression, as determined on the basis of a composite of clinical, radiological, and mycological criteria.

Progression: Evidence of progressive fungal disease based on a composite of clinical, radiological, and mycological criteria.

Death: Death during the prespecified period of evaluation, regardless of attribution.

Survival data (overall mortality and attributable mortality, if applicable) for all patients and the time-to-negativity of a blood culture will be reported in this study.

Anidulafungin in Patients With Hematologic Malignancies

Anidulafungin in Patients With Hematologic Malignancies - An Open-label, Prospective Study to Evaluate the Safety Profile at Prophylactic and Therapeutic Dosages

Pfizer

Elisabethinen Hospital

OA Dr. Michael Girschikofsky

Syndrome

Neutropenia

Genetic Predisposition to Disease

Disease Susceptibility

Immune Reconstitution Inflammatory Syndrome

Agranulocytosis

Leukopenia

Cytopenia

Leukocyte Disorders

Chronic Graft Versus Host Disease

Granulocytopenia

Fluorodeoxyglucose F18

Radiopharmaceuticals

to determine whether F18 fluorodeoxyglucose (18F-FDG) positron-emission tomography scan (PET scan) is useful for the therapy strategy of hepatosplenic candidiasis.

18F-FDG PET Scan

The purpose of this study is to determine whether F18 fluorodeoxyglucose (18F-FDG) positron-emission tomography scan (PET scan) is useful for the therapy strategy of hepatosplenic candidiasis.

Chronic disseminated candidiasis, often referred to as hepatosplenic candidiasis (HSC), is an infection due to Candida spp. that mainly involves the liver and spleen. HSC occurs mostly in patients with profound and prolonged neutropenia, which is more often seen in patients with hematologic malignancies. Despite an appropriate antifungal prophylaxis, the incidence of HSC in France might be closed to 5% in patients suffering from acute leukemia. Early and adequate diagnosis and treatment of HSC are crucial, as treatment delays can negatively affect the prognosis of the underlying condition. Current guidelines recommend a 6-month duration treatment. Prolonged treatments up to 6 months are frequent, leading to antifungal toxicity and cost increase. Preliminary study by our team has already assessed F18 fluorodeoxyglucose (18F-FDG) positron-emission tomography scan (PET scan) as a diagnostic tool for HSC. 18F-FDG PET scan could be helpful in the diagnosis, follow-up and therapy strategy of HSC, helping to stop antifungal treatment. Other molecular, immunological and serological tools have to be developed in order to avoid hepatic biopsies. Actually, mycological evidence of infection is found in only 20% of the cases. The pathogenesis of HSC is also not well understood, but it is believed that it may be due to an unbalanced adaptive immune response that leads to an exacerbated inflammatory reaction, resulting in an Immune Reconstitution Inflammatory Syndrome (IRIS). In that context, a better understanding of the disease pathophysiology and of the potential genetic susceptibility could have an impact on therapy strategy. For example, new approaches such as the use of adjuvant high-dose corticosteroids have been shown beneficial. This study is the first step to improve HSC diagnosis and therapy strategy.

Hepatosplenic CANdidiasis : PETscan and Immune Response Analysis

Multicenter Prospective Pilot Study Investigating Pathophysiology, Diagnostic and Therapeutic Strategies of Hepatosplenic Candidiasis

Clinical assessment (no fever) and PET scan assessment (intensity of liver and/or spleen lesions)

Comparison between Day 0 and Month 3 exams

Measurement of beta-1,3-D-glucans, mannan/anti-mannan, anti-Saccharomyces cerevisiae antibodies in comparison with controls.

Assessment of a new real-time PCR on serum and hepatic tissue

Measurement of cytokines and lymphocytes populations on serum and hepatic tissue in comparison with controls

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prevention of Invasive Fungal Infections (IFIs) in Subjects Receiving Chemotherapy for Acute Lymphoblastic Leukemia	NCT01259713	Invasive Fungal...	Liposomal ampho... Placebo	18 Years -	Gilead Sciences
A Study of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients	NCT03241550	Hematological M...	isavuconazonium... isavuconazonium...	1 Year - 17 Years	Astellas Pharma Inc
Prevention of Invasive Fungal Infections (IFIs) in Subjects Receiving Chemotherapy for Acute Lymphoblastic Leukemia	NCT01259713	Invasive Fungal...	Liposomal ampho... Placebo	18 Years -	Gilead Sciences
A Study of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients	NCT03241550	Hematological M...	isavuconazonium... isavuconazonium...	1 Year - 17 Years	Astellas Pharma Inc
A Study of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients	NCT03241550	Hematological M...	isavuconazonium... isavuconazonium...	1 Year - 17 Years	Astellas Pharma Inc
Anidulafungin in Patients With Hematologic Malignancies	NCT01053884	Hematologic Mal...	Anidulafungin	18 Years -	Elisabethinen Hospital
Hepatosplenic CANdidiasis : PETscan and Immune Response Analysis	NCT01916057	Invasive Fungal... Chronic Dissemi... Hematological M... Hematopoietic S... Neutropenia	18F-FDG PET Sca...	18 Years -	Assistance Publique - Hôpitaux de Paris

Spots Global Cancer Trial Database for invasive fungal disease