Infections

All Conditions

Neoplasms

Blood and Lymph Conditions

Symptoms and General Pathology

Musculoskeletal Diseases

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Hematologic Neoplasms

Communicable Diseases

Invasive Fungal Infections

Bone Neoplasms

Bacterial Infections

Bacterial Infections and Mycoses

Anti-Infective Agents

All Drugs and Chemicals

Voriconazole

Clotrimazole

Miconazole

Antifungal Agents

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Hormones

Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

Voriconazole Starting oral dose of 400 mg pills twice a day for first day, followed by 200 mg by mouth twice a day thereafter.

Voriconazole 6 mg/kg by vein (IV) first dose then 200 mg pills two times a day thereafter.

Starting dose of 400 mg by mouth twice a day for first day, followed by 200 mg by mouth twice a day thereafter.

6 mg/kg by vein for first dose, followed by 200 mg by mouth twice a day thereafter.

Jorge Cortes, MD

Objectives:

To investigate the relationship between the administration of intravenous (IV) and oral voriconazole (vori) and the occurrence of false positive (1,3) beta-d- glucan (BG) relative to the standard assessment criteria used to diagnose invasive fungal infection in patients with hematologic malignancies.

Chemotherapy can lower immune system function, which can cause fungal infections to occur more easily. These fungal infections are found by certain blood tests. One of these blood tests looks for a part of the fungal cell floating freely in the human blood.

When certain drugs are given to patients to prevent fungal infections, these blood tests may show that there is an infection when there actually is not one present. Some of these drugs are similar to the study drug voriconazole.

The Study Drug:

Voriconazole is designed to slow the growth of fungal cells, which may cause the fungal cells to die.

Screening Tests:

Signing this consent form does not mean that you will be able to take part in this study. You will have "screening tests" to help the doctor decide if you are eligible to take part in this study. The following tests and procedures will be performed:

* Your medical history will be recorded.
* You will have a complete physical exam.
* Blood (about 1 teaspoon) will be drawn for routine tests.
* If your doctor thinks it is needed, you will have a chest x-ray or computed tomography (CT) scan of the chest to check for pneumonia.

The study doctor will discuss the screening test results with you. If the screening tests show that you are not eligible to take part in the study, you will not be enrolled. Other treatment options will be discussed with you.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to 1 of 2 study groups. Group 1 will consist of the first 10 patients enrolled on the study. Group 2 will consist of the next 10 patients enrolled on the study. If you are in Group 1, you will take only pills of study drug 2 times every day while you are on study. If you are in Group 2, you will receive the study drug through a needle in your vein 1 time when you begin the study and then take pills of study drug 2 times every day for the rest of the time you are on study.

Blood Draws for Fungal Infection Tests:

If you are in Group 1, blood (about 1 teaspoon each time) will be drawn for fungal infection tests at the following times:

* Before the first dose of study drug.
* 1, 2, 4, and 8 hours after the first dose of study drug.
* Before the third dose of study drug.
* 1, 2, 4, and 8 hours after the third dose of study drug.

If you are in Group 2, blood (about 1 teaspoon each time) will be drawn for fungal infection tests at the following times:

* Before the first dose of study drug.
* 1, 2, 4, and 8 hours after the first dose of study drug.
* 1, 2, and 4 hours after the second dose of study drug.

Length of Study:

You may continue taking the study drug for up to 35 days if you are receiving chemotherapy for the first time and up to 42 days if you have had chemotherapy before. Your doctor may decide that you should take the study drug for an even longer period of time or that you need to have another drug to prevent fungal infections. You will be taken off study if intolerable side effects occur or if you get a fungal infection.

Additional Information:

There are several drugs that should not be taken in combination with voriconazole. You should talk to the study doctor about any drugs you may be taking and about any drugs you may plan to start taking while on study. You should also avoid eating/drinking grapefruit/grapefruit products while you are on study, as they may interfere with the effects of the study drug.

This is an investigational study. Voriconazole is FDA approved and commercially available for the treatment of fungal infections.

Up to 20 patients who are found to be eligible after screening will take part in this study. All will be enrolled at M. D. Anderson.

Beta Glucan Assay in Patients Receiving Voriconazole Prophylaxis

Kinetics of 1, 3 Beta-d- Glucan Assay in Patients With Hematologic Malignancies Receiving Voriconazole Prophylaxis

Rate calculated as number of participants with positive levels divided by total number of participants. beta-d-glucan (BG), a cell wall constituent of fungi, can be detected in serum as a marker of Invasive fungal infections (IFI).

Blood samples were drawn on first 2 days of treatment at baseline (before the drug) and at 1, 2, 4, 8 hours after the first dose of the day. BG serum levels were measured using the Fungitell assay, using a cut off value of 60 pg/ml for positivity.

Pfizer

M.D. Anderson Cancer Center

Voriconazole starting oral dose of 400 mg pills twice a day for first day, followed by 200 mg by mouth twice a day thereafter.

Group 1 - Oral

Group 2 - IV + Oral

Total

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

Jorge Cortes, MD / Professor

Samples BG levels > 60pg/ml, First Test

Samples BG levels > 60pg/ml, Following Re-Test

Analysis was intent to treat with a total of 182 samples (mean 8.6 samples/participant) drawn from participants.

Percentage of Samples With BG Levels > 60pg/ml

Overall Study

Rare Diseases

Neoplasms by Histologic Type

Hematologic Diseases

Acute Graft Versus Host Disease

Amphotericin B

Liposomal amphotericin B

Antiprotozoal Agents

Antiparasitic Agents

Ambisome

Lamine Mahi, MD

This pilot study was designed in order to evaluate the safety and efficacy of an AmBisome loading dose regimen, in a weekly administration schedule, during the aplastic phase following induction or consolidation chemotherapy for acute leukaemia, and during the initial phase of allogeneic stem-cell transplant, which are both high risk periods as far as severe fungal infections development is concerned.

PROPHYSOME: Pilot Study on Safety of a Weekly Administration of 10mg/kg of AmBisome® in Antifungal Prophylaxis Treatment of Allogeneic Stem-cell Transplantation and Acute Leukaemia

Pilot Study on Safety of a Weekly Administration of 10mg/kg of AmBisome® in Antifungal Prophylaxis Treatment of Allogeneic Stem-cell Transplantation and Acute Leukaemia

Gilead Sciences

Wounds and Injuries

Hyperthermia

Neutropenia

Fever

Agranulocytosis

Leukopenia

Cytopenia

Leukocyte Disorders

Granulocytopenia

Pharmaceutical Solutions

Itraconazole

Hydroxyitraconazole

Participants who have been receiving itraconazole will be observed prospectively. Itraconazole will be administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, followed by itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia is recovered.

Itraconazole will be administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, followed by itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia is recovered.

Janssen Korea, Ltd., Korea Clinical Trial

The purpose of this observational study is to investigate whether a sufficient concentration of itraconazole can influence disappearance of a fever (defeverscence) when intravenous (into the vein) itraconazole is administered for resolving unknown neutropenic fever of participants who are given itraconazole oral solution as a prophylaxis under general treatment conditions.

This is a prospective (study following patients forward in time), open-label (all people know the identity of the intervention), multi-center (conducted in more than one center) observational study to examine the correlation between a sufficient blood concentration of itraconazole and disappearance of a fever (defeverscence) when itraconazole injection is administered for resolving unknown neutropenic fever of participants who are given itraconazole oral solution as a prophylaxis under general treatment conditions. The recommended dose of the drug will be 200 milligram (mg), which will be administered intravenously, twice daily for 2 days (a total of 4 doses) and then 200 mg once daily for 12 days. After the administration for a total of 14 days, itraconazole oral solution 200 mg (which is equivalent to 20 ml) twice daily will be continued for a total of 14 days until clinically significant neutropenia is resolved.

The Relationship of Defeverscence and Itraconazole Plasma Level Study in Immunocompromised Participants

The Relationship of Defeverscence and Itraconazole Plasma Level Using Sporanox IV as an Empiric Therapy in Immunocompromised Patients Who Have Been Treated With Sporanox Oral Solution as Prophylaxis

Percentage of participants who achieved more than or equal to 1000 ng/ml level after administration of study treatment were reported. Plasma level of itraconazole was defined as the sum of itraconazole concentration (IC) and hydroxyitraconazole concentration (HIC).

Defervescence was defined as fall of the body temperature below 38.0 degree Celsius (C) at least once after starting to receive the study treatment.

The mean time to defervescence was reported in participants who received the study treatment. Defervescence was defined as fall of the body temperature below 38.0 degree C at least once after starting to receive the study treatment.

The duration of neutropenia was reported. Neutropenia was defined as neutrophil count less than or equal to (\<=) 500 cells per cubic millimeter (cells/mm\^3), or neutrophil count \<=1000 cells/mm\^3 and anticipated to decrease to \<=500 cells/mm\^3 within several days.

The mean values for ANC based on blood tests performed on Day 0 (before starting the study treatment) constitute a Baseline measure for ANC.

Defervescence was defined as fall of the body temperature below 38.0 degree C at least once after starting to receive the study treatment. Plasma level of itraconazole was defined as the sum of IC and HIC.

Plasma level of itraconazole was defined as the sum of IC and HIC. The OSR was defined based on satisfaction of the following criteria: (1) participants if treated for baseline fungal infection, there was either eradication (removal of fungus in culture), or presumed eradication; no evidence in culture but appeared to be treated clinically, (2) absence of breakthrough fungal infection during the treatment and for 7 days after completing the treatment, (3) survival for 7 days after completing the treatment, (4) absence of early withdrawal due to adverse events or lack of efficacy, and (5) defervescence. The presence and absence of OS was reported.

Blood cultures (a laboratory test on a sample of blood) were assessed to identify fungus. Percentage of participants with presence or absence of fungus before starting the study drug were calculated.

Plasma level of itraconazole was defined as the sum of IC and HIC. A breakthrough fungal infection was defined as any fungal infection that was diagnosed more than (\>) 3 days on or during therapy or within 7 days after completion of therapy. Blood cultures were assessed to identify fungus.

Janssen Korea, Ltd., Korea

Participants who had been receiving itraconazole were observed prospectively. Itraconazole was administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, and then itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia was recovered.

Baseline characteristics were reported only for intent-to-treat (ITT) population which included 150 participants.

Clinical Research Associate

The intent-to-treat (ITT) population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once.

Percentage of Participants Achieving Plasma Level of Itraconazole at 1000 Nanogram Per Milliliter (ng/mL) or Higher After Administration of Study Treatment

The ITT population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once.

Percentage of Participants With Deferevescence After Administration of Study Treatment

The ITT population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.

Mean Time to Defervescence in Participants Who Received the Study Treatment

Duration of Neutropenia

Absolute Neutrophil Count (ANC)

IC+HIC < 1000ng/mL (n=48)

IC+HIC >= 1000ng/mL (n=102)

The ITT population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once. Here, 'n' signifies participants who were evaluable for this measure at given time points.

Percentage of Participants With Defervescence by Plasma Level of Itraconazole

Presence of OS (n=95)

Absence of OS (n=39)

The ITT population included the participants who satisfied the eligibility criteria, received the study drug at least once, and in whom the primary efficacy endpoint was measured at least once. Here, 'N' (number of participants analyzed) = participants evaluable for this measure and 'n' = participants evaluable for given category.

Plasma Concentration of Itraconazole by Overall Success Rate (OSR) in Participants Who Received the Study Treatment

Percentage of Participants With Baseline Fungal Infection

Presence of Breakthrough Fungal infection (n=128)

Absence of Breakthrough Fungal infection (n=6)

Plasma Concentration of Itraconazole by Breakthrough Fungal Infection

Disease Attributes

Posaconazole

Adult (≥ 18 years old) patients with a hematologic malignancy receiving posaconazole prophylaxis (oral tablets or IV administration) for:

i) Induction, consolidation or re-induction chemotherapy for acute leukemia or myelodysplastic syndrome (i.e. expected duration of neutropenia post-chemotherapy of ≥ 10 days) OR ii) Allogeneic hematopoietic stem cell transplant recipients during the post-transplantation phase (100-day post-transplantation) or later in case of intensified immunosuppression for moderate to severe graft vs host disease (GVHD).

AND

iii) Being diagnosed with proven or probable bIMI according to the EORTC-MSGERC classification (10) while on continuous posaconazole prophylaxis for at least 7 days.

For each bIMI case, we will include 2 control cases fulfilling the following criteria:

i) Receiving continuous posaconazole prophylaxis for at least 7 days

ii) No diagnosis of proven, probable or possible IMI according to EORTC-MSGERC classification (10) during the entire hospital stay

Frederic Lamoth

Cornelia Lass-Flörl

Jannick Stemler

Nina Khanna

Stefan Zimmerli

Véronique Erard

Dionysios Neofytos

Kattia Boggian

Invasive mold infections (IMI) mainly affect patients with hematologic malignancies receiving intensive chemotherapy or after hematopoietic stem cell transplantation (HSCT). Prolonged neutropenia after remission induction chemotherapy (\>10 days duration) and continuous immunosuppression in the context of prevention or therapy of graft versus host disease (GVHD) for HSCT recipients (first 100 days post-transplantation and thereafter if GVHD is present) are considered as periods at high risk of IMI.

Posaconazole prophylaxis is prescribed according to current guidelines to reduce the occurrence of IMI. Nevertheless, breakthrough IMI (bIMI), i.e. IMI occurring under mold-active prophylaxis, are still observed.

The investigators hypothesized that the epidemiology of bIMI (under posaconazole prophylaxis) differs from that of IMI occurring in the absence of mold-active antifungal prophylaxis. Because bIMI are rare events since the introduction of posaconazole prophylaxis, epidemiological data of bIMI are scarce.

This study aims to i) describe the epidemiology, clinical features, treatment and outcome of bIMI, ii) assess the causes of bIMI, iii) determine potential risk factors associated with the developllement of bIMI iv) assess the impact of bIMI on overall mortality.

Design

Retrospective and prospective, observational, case-control, multicenter, international study.

The retrospective part will enroll previously identified bIMI cases and control cases (1:2) over the last five years: October 1st 2015 to September 30st 2020.

The prospective part will enroll bIMI cases and control cases (1:2) occurring over a two-year period: October 1st 2020 to September 30st 2022.

Setting

The aim is to enroll 10 to 15 European centers with dedicated units for hematologic cancer patients. Currently, six centers have confirmed their participation (from Switzerland and Germany).

Study Population

Adult (≥ 18 years old) patients with a hematologic malignancy receiving posaconazole prophylaxis during induction, consolidation or re-induction chemotherapy or after HSCT.

Cases : patients receiving posaconazole prophylaxis for at least 7 days and diagnosed with bIMI proven or probable according to EORTC-MSGERC.

Controls: patients receiving posaconazole prophylaxis for at least 7 days, without diagnosis of bIMI possible, probable or proven according to EORTC-MSGERC.

The objective is to enroll about 100 bIMI cases and 200 controls.

Breakthrough Invasive Mold Infections Under Posaconazole Prophylaxis (BIMI)

Multicenter Case-control Study of Breakthrough Invasive Mold Infections Under Posaconazole Prophylaxis

* Assessment of the cause of bIMI (intrinsically resistant mold pathogen vs susceptible mold pathogen but insufficient posaconazole serum concentration vs unknown)
* Description of clinical features, treatment and outcome of bIMI

• Univariate and multivariate analyses of the parameters associated with an increased risk of bIMI (in particular, the association of a threshold of posaconazole concentration and bIMI) by comparison of bIMI cases with controls (posaconazole prophylaxis and no bIMI)

• Comparison of mortality rate (6 and 12 weeks) between bIMI and control cases.

• Univariate and multivariate analysis of predictors of mortality (6 and 12 weeks) among bIMI cases.

Centre Hospitalier Universitaire Vaudois

Principal investigator

Syndrome

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Anidulafungin

Day 1-15: anidulafungin 200 mg q48h IV maintenance dose (8 dosages)

Day 1-13: anidulafungin 300 mg q72h IV maintenance dose (5 dosages)

anidulafungin 200 mg q48h

anidulafungin 300 mg q72h

R Brüggemann, PharmD

The purpose of this study is to study the pharmacokinetics of anidulafungin (Ecalta ®) given intravenously as antifungal prophylaxis to recipients of an allogeneic haematopoietic stem cell transplant following myeloablative chemotherapy or patients receiving intensive chemotherapy for AML-MDS who are at high risk for developing invasive fungal disease.

Alternate dosing strategies of echinocandin drugs might provide a better efficacy in the treatment of fungal infections as compared to the current label dosing strategy. Before conducting a controlled efficacy trial of echinocandins in haematology patients, the pharmacokinetics of these alternate dosing strategies need to be tested before bringing this idea to practice in a large randomised trial.

Therefore we want to conduct a pharmacokinetic study with anidulafungin given every 48 hours or every 72 hours. This research can be performed best in a group of patients at high risk for developing invasive fungal infections.

Recipients of an allogeneic haematopoietic stem cell transplant (HSCT) or patients receiving intensive chemotherapy for acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) are at a relatively high risk of developing invasive fungal infections and are therefore candidates for primary prophylaxis. However, the options are limited to fluconazole which affords no protection against mould infections. Amphotericin B is not considered useful because of its desoxycholate formulation has too many side effects and its lipid formulations are too expensive nor have the broad-spectrum triazoles itraconazole and voriconazole proved their value in this setting. Anidulafungin is the first of a new class of antifungal drugs quite unlike any others attacking specifically the ß 1-3 -D-glucan synthase of the cell wall. It has relatively few side effects and appears safe and effective for treating Aspergillus and Candida infections. Since these two genera account for 90% of fungal infections in HSCT recipients the drug would seem an ideal candidate for prophylaxis.

Importantly, nothing is known about the pharmacokinetics of alternate dosing regimens of anidulafungin in this patient population. Therefore a pharmacokinetic study of a homogenous cohort of patients is necessary to test the assumption, that adequate exposure is obtained with alternate dosing and that it is safe.

Pharmacokinetics of Anidulafungin (Ecalta ®) Intravenous Given to Patients at High Risk for Developing Invasive Fungal Disease

Pharmacokinetics of Anidulafungin Given Intravenously as Antifungal Prophylaxis to Recipients of an Allogeneic Haematopoietic Stem Cell Transplant Following Myeloablative Chemotherapy or Patients Receiving Intensive Chemotherapy for AML-MDS

comparison of pharmacokinetics of anidulafungin given once in every two days or once in every three days

To determine whether adequate exposure is attained by patients undergoing an allogeneic haematopoietic stem cell transplant following myeloablative chemotherapy or receiving intensive chemotherapy for AML-MDS when using a q48 hour or a q72 hour dosing regimen

To determine the safety of anidulafungin in the patient population

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Beta Glucan Assay in Patients Receiving Voriconazole Prophylaxis	NCT00904995	Leukemia Fungal Infectio...	Voriconazole Voriconazole	18 Years -	M.D. Anderson Cancer Center
PROPHYSOME: Pilot Study on Safety of a Weekly Administration of 10mg/kg of AmBisome® in Antifungal Prophylaxis Treatment of Allogeneic Stem-cell Transplantation and Acute Leukaemia	NCT00362544	Leukemia	Ambisome	18 Years -	Gilead Sciences
PROPHYSOME: Pilot Study on Safety of a Weekly Administration of 10mg/kg of AmBisome® in Antifungal Prophylaxis Treatment of Allogeneic Stem-cell Transplantation and Acute Leukaemia	NCT00362544	Leukemia	Ambisome	18 Years -	Gilead Sciences
Beta Glucan Assay in Patients Receiving Voriconazole Prophylaxis	NCT00904995	Leukemia Fungal Infectio...	Voriconazole Voriconazole	18 Years -	M.D. Anderson Cancer Center
The Relationship of Defeverscence and Itraconazole Plasma Level Study in Immunocompromised Participants	NCT01021683	Hematologic Neo... Neutropenia Fever	Itraconazole	20 Years -	Janssen Korea, Ltd., Korea
The Relationship of Defeverscence and Itraconazole Plasma Level Study in Immunocompromised Participants	NCT01021683	Hematologic Neo... Neutropenia Fever	Itraconazole	20 Years -	Janssen Korea, Ltd., Korea
Breakthrough Invasive Mold Infections Under Posaconazole Prophylaxis (BIMI)	NCT04720144	Invasive Mold I... Breakthrough In... Hematologic Mal... Hematologic Dis...		18 Years -	Centre Hospitalier Universitaire Vaudois
Breakthrough Invasive Mold Infections Under Posaconazole Prophylaxis (BIMI)	NCT04720144	Invasive Mold I... Breakthrough In... Hematologic Mal... Hematologic Dis...		18 Years -	Centre Hospitalier Universitaire Vaudois
Pharmacokinetics of Anidulafungin (Ecalta ®) Intravenous Given to Patients at High Risk for Developing Invasive Fungal Disease	NCT01249820	Leukemia Myelodysplastic... Leukemia, Myelo...	anidulafungin 2... anidulafungin 3...	18 Years - 64 Years	Radboud University Medical Center

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