Neoplasms

Blood and Lymph Conditions

All Conditions

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Aspergillosis

Invasive Pulmonary Aspergillosis

Pulmonary Aspergillosis

Neoplasms by Histologic Type

Hematologic Diseases

Mycoses

Bacterial Infections

Communicable Diseases

Bacterial Infections and Mycoses

Lung Diseases

Lung Diseases, Fungal

Respiratory Tract Diseases

Invasive Fungal Infections

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

All Drugs and Chemicals

Clotrimazole

Miconazole

Antifungal Agents

Caspofungin

Olorofim

Enzyme Inhibitors

Patients will receive F901318 intravenously, starting 24 - 72 h after last chemotherapy infusion:

* Day 1: 4.0 mg/kg i.v. b.i.d.
* Day 2 until resolution of neutropenia (max. until day 14): 2.0 mg/kg i.v. b.i.d.
* Day after last i.v. application: 2.0 mg/kg oral q.d.

Concomitant medication:

For Candida prophylaxis, concomitant caspofungin will be administered from the 4th day of chemotherapy until end of neutropenia:

* Chemo day 4: Caspofungin 70 mg i.v. q.d.
* Chemo day 5 until resolution of neutropenia or until end of F901318 treatment (day 15): Caspofungin 50 mg i.v. q.d.

All patients will undergo chemotherapy for acute leukaemia according to local clinical standard.

F901318 treatment starting after completion of chemotherapy. Max. 14 days of intravenous F901318 b.i.d. treatment, followed by one oral dose of F901318. Loading doses 4 mg/kg b.i.d. , maintenance doses 2 mg/kg b.i.d.

F901318

Intravenous Caspofungin treatment starting during chemotherapy for concomitant prophylaxis of fungal infection. Loading dose 70 mg q.d., maintenance doses 50 mg q.d.

Oliver Cornely, PhD, MD

This study assesses the pharmacokinetics and safety of the new antifungal F901318 in AML patients.

F901318 has potent in vitro efficacy against Aspergillus spp. including azole-resistant strains and consistent efficacy in in vivo mouse models of infection. F901318 is active by both oral and intravenous routes of administration in preclinical efficacy studies.

Non-clinical studies and phase I clinical trials show that F901318 has a good overall safety profile and limited potential for drug-drug interactions. F901318 exhibits a highly promising profile which can potentially address the critical treatment requirements for invasive Aspergillus infections in a changing clinical environment in which new classes of antifungals are needed.

This phase IIa study aims to confirm PK and safety information of F901318 from phase I and bridge them to a neutropenic AML patient population, which represents the main population for future efficacy trials. Coadministration of caspofungin will allow recognizing potential factors of suboptimal F901318 exposure without the risk of fatal disseminating infection.

Study on Safety and Pharmacokinetics of Intravenous F901318 for Fungal Prophylaxis in AML Patients

An Open Label Phase IIa Clinical Study to Evaluate the Safety and Pharmacokinetics of Intravenous and Oral F901318 (Combined With Caspofungin) for Antifungal Prophylaxis in Patients Undergoing Chemotherapy for Acute Myeloid Leukaemia

F901318 trough level assessment for 14 days once per day. On three of these 14 days additional samples for determination of plasma concentration of F901318 will be collected.

Measurement 2h, 4h, 12h and 24h after oral intake of F901318

Patients galactomannan index and body temperature will be assessed regularly. If it is clinically indicated the patients will undergo a CT, which will be checked for infiltrations. If infiltrations are detected the patients will undergo a bronchoalveolar lavage, the result of which will be used to analyse BAL GMI, to grow a microbiological culture, to perform histology and perform an Aspergillus PCR. On the basis of the available data for each patient the scientific advisory committee will assess the number of patients suffering from a possible/probable or proven IFD.

University Hospital of Cologne

F2G Biotech GmbH

Hematologic Neoplasms

Pharmaceutical Solutions

Itraconazole

Hydroxyitraconazole

Cytochrome P-450 Enzyme Inhibitors

Hormones

Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

Participants will receive 200 milligram (mg) of itraconazole intravenously (IV) twice daily on Day 1 and Day 2, followed by 200 mg once daily through Day 14. From Day 15 to Day 28, participants will receive 200 mg (20 milliliters \[mL\]) of itraconazole oral solution orally twice daily. Participants, who are not suitable for oral administration of itraconazole based on the investigator's judgment, will receive 200 mg of itaconazole IV once daily from Day 15 to Day 28.

Participants will receive 70 mg of caspofungin IV once daily on Day 1 followed by 50 mg IV infusion once daily thereafter through Day 28.

Xian-Janssen Pharmaceutical Ltd., China Clinical Trial

The purpose of this study is to investigate the hypothesis that the efficacy of intravenous (IV) itraconazole followed by oral itraconazole is non-inferior to that of intravenous caspofungin as empiric therapy for suspected fungal infection participants with fever and neutropenia.

A Study Comparing the Efficacy of Intravenous Followed by Oral Itraconazole With Intravenous Caspofungin For Empiric Antifungal Therapy in Neutropenic Participants With Hematological Malignancy

A Multicenter, Randomized Trial Comparing The Efficacy of Intravenous Followed by Oral Itraconazole With Intravenous Caspofungin For Empiric Antifungal Therapy in Neutropenic Subjects With Hematological Malignancy

Response rate in each of the 2 treatment groups will be measured by the percentage of participants that achieve all of the following 5 composite endpoints: 1) survival for 7 days after completion of treatment, 2) absence of breakthrough invasive fungal infection during the study drug administration and within the first 7 days after completion of treatment, 3) successful treatment of baseline fungal infection, 4) defervescence and 5) no premature withdrawal from the study due to drug-related toxicity or lack of efficacy.

Absence of breakthrough invasive fungal infection is defined as the clinically or/and microbiologically documented fungal infection with an onset on or after day 3 of the study treatment during the study drug administration and within the first 7 days after completion of treatment.

Successful treatment of baseline fungal infection is defined as the clinically and microbiologically documented fungal infection with an onset within screening to 2 days after the study treatment.

Defervescence is defined as oral/rectal temperature less than (\<) 38 degree celsius or axillary temperature (\<) 37.5 degree celsius for over 48 hours) during the period of neutropenia.

Response rate will be measured by the percentage of participants (who received oral administration of itraconazole) that achieve all of the following 5 composite endpoints: 1) survival for 7 days after completion of treatment, 2) absence of breakthrough invasive fungal infection during the study drug administration and within the first 7 days after completion of treatment, 3) successful treatment of baseline fungal infection, 4) defervescence and 5) no premature withdrawal from the study due to drug-related toxicity or lack of efficacy.

Xian-Janssen Pharmaceutical Ltd.

Patients will receive caspofungin, starting from the first day of induction chemotherapy for leukemia, as a single daily dose intravenously at the dosage of 70 mg q.d. and followed by 50 mg q.d. thereafter until documentation of complete hematologic remission after the first induction cycle or of leukemia persistence after one cycle of induction and one cycle of salvage chemotherapy.

No stratification is planned.

Giuseppe Rossi, MD

Chiara Cattaneo

* To assess the overall clinical yield - in terms of efficacy and safety endpoints of adding caspofungin as prophylaxis of Invasive Pulmonary Aspergillosis in patients undergoing induction treatment for newly diagnosed acute leukemia
* To investigate the prognostic significance of Ptx3 at diagnosis and during the first chemotherapy cycle with respect to the development of IPA

Invasive aspergillosis (IA), and particularly invasive pulmonary aspergillosis (IPA), is an important cause of morbidity and mortality in patients who are receiving chemotherapy for acute leukemia (AL), being the the most common invasive mycosis which develops in these patients. Proven invasive aspergillosis has been reported in 6,5% of patients with acute leukemia in a retrospective multicenter study (Pagano, Haematologica 2001) but that frequency may be underestimated, since definite diagnosis is difficult to obtain, particularly in leukemic patients.

When the recently developed, internationally recognized IFIGC/MSG/EORTC diagnostic criteria were retrospectively applied to a consecutive series of acute leukemia patients, the overall frequency of IPA was 25,3% (proven/probable 8,5%; possible 16,9%). Criteria for a diagnosis of IPA were fulfilled in 62,8% of pulmonary infiltrates developing in AL patients (proven/probable 17,1%; possible 45,7%). IPA developed both in AML and in ALL patients. Proven/probable IPA developed in 83% of cases during the first induction cycle (Borlenghi, EHA 2003). It may be estimated that such figures would be higher when patients would be followed prospectively and strictly monitored, particularly with GM antigenemia.

The mechanisms by which common colonizing agents like Aspergillus spp. can become invasive pathogens and cause severe tissue damage are only partially known. Recent experimental data in animal models raised the hypothesis that the long pentraxin Ptx3 may play an important role in resistance to selected microbial agents, in particular to Aspergillus fumigatus (Garlanda, Nature 2002).

Caspofungin is an echinocandin with potent antifungal activity against Aspergillus species. Its mechanism of action differs from that of the antifungal agents used so far, like amphotericin and azoles. It has proven effective and well tolerated and its use is therefore currently approved as salvage treatment in patients with invasive aspergillosis refractory to amphotericin, as well as for the empiric treatment of febrile neutropenia. Indeed it has been recently evaluated as empirical treatment in neutropenic patients with persistent fever of unknown origin and proved equally effective and better tolerated than liposomal amphotericin.

There are as yet no data on the use of caspofungin as primary prophylaxis in patients with acute leukaemia, a setting in which the lack of effective preventive treatments together with the generally favourable safety profile and efficacy of caspofungin makes it particularly attractive for investigation.

It can be hypothesized from the above data that the administration of caspofungin as prophylactic treatment of invasive aspergillosis should be safe and well tolerated by patient undergoing chemotherapy for acute leukemia at diagnosis.

It may reduce the high incidence of invasive pulmonary aspergillosis which characteristically develops during the first course of induction treatment, avoiding the direct morbidity and mortality of IPA and its negative impact on the treatment and prognosis of AL as well as the costs for IPA diagnosis and treatment.

The serum levels of the long pentraxin Ptx3 may have interpatient variability and may correlate with the subsequent development of invasive aspergillosis.

These facts led to the present multicenter, phase II, single arm, open study, performed by the Northern Italy Leukemia Group. There will be approximately 12 participating centers, which will enroll a total of 100 patients. Patients will receive caspofungin, starting from the first day of induction chemotherapy for leukemia, as a single daily dose intravenously at the dosage of 70 mg q.d. and followed by 50 mg q.d. thereafter until documentation of complete hematologic remission after the first induction cycle or of leukemia persistence after one cycle of induction and one cycle of salvage chemotherapy.

No stratification is planned. Patients will concurrently receive all the medications needed for the treatment of acute leukemia,according to the ongoing protocols of NILG for acute leukemia at diagnosis. The study period continues

The treatment will be stopped in the presence of any of the following conditions:

* Development of a severe adverse event or of any grade 3-4 toxicity attributable to caspofungin
* Development of proven/probable IPA No caspofungin dose reduction is planned. The dose of caspofungin will be adjusted when patients weight is over 80 kgs and in patients taking rifampin or other liver enzymes-inducing drugs.

Prophylaxis of Fungal Invasive Infections in Leukemia

A Multicenter Phase II Study to Evaluate the Safety, Tolerability and Efficacy of Caspofungin as Prophylactic Treatment of Invasive Fungal Infections in Patients With Acute Leukemia Undergoing Induction Chemotherapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study on Safety and Pharmacokinetics of Intravenous F901318 for Fungal Prophylaxis in AML Patients	NCT02856178	Pulmonary Asper... Acute Myeloid L...	F901318 Caspofungin	18 Years -	F2G Biotech GmbH
A Study Comparing the Efficacy of Intravenous Followed by Oral Itraconazole With Intravenous Caspofungin For Empiric Antifungal Therapy in Neutropenic Participants With Hematological Malignancy	NCT02895529	Hematologic Neo...	Itraconazole Caspofungin	18 Years -	Xian-Janssen Pharmaceutical Ltd.
A Study Comparing the Efficacy of Intravenous Followed by Oral Itraconazole With Intravenous Caspofungin For Empiric Antifungal Therapy in Neutropenic Participants With Hematological Malignancy	NCT02895529	Hematologic Neo...	Itraconazole Caspofungin	18 Years -	Xian-Janssen Pharmaceutical Ltd.
Prophylaxis of Fungal Invasive Infections in Leukemia	NCT00501098	Invasive Pulmon...	Caspofungin	18 Years -	Northern Italy Leukemia Group

Spots Global Cancer Trial Database for caspofungin

Every month we try and update this database with for caspofungin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for caspofungin

Every month we try and update this database with for caspofungin cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for caspofungin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.