Anidulafungin in Patients With Hematologic Malignancies

NCT01053884 | Terminated Phase 2

• 2 other identifiers: Anidulafungin - MG-ECALTA12009-014527-23
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hematologic Malignancies

Keywords

Invasive Candidiasis; invasive fungal disease; Anidulafungin

Outcome Measures

Primary Outcomes (1)

• Safety: incidence of (serious)adverse events and changes of important laboratory parameters (in particular liver and renal function parameters) with clinical impact will be reported.

  day 1-5, 10 , end of treatment and study.

Secondary Outcomes (1)

• pharmacokinetics and efficacy: As prophylaxis: the number of breakthrough infections. As treatment: complete and partial response rate (success); stable, progression and death (Failure)

  day 5 (pharmacokinetics), end of treatment, week 6 and 12 (efficacy)

Study Arms (1)

Anidulafungin, safety, antifungal drug

OTHER

single arm study

Drug: Anidulafungin

Interventions

Anidulafungin DRUG

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.

Also known as: Ecalta

Anidulafungin, safety, antifungal drug

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (≥ 18 years) with a hematologic disorder AND an indication for IFI prophylaxis or therapy, but a relative contraindication for azoles or polyenes due to hepatic or renal dysfunction\*, are scheduled to receive anidulafungin for one of the following specific indications:
• Need for primary antifungal prophylaxis in patients with Acute leucaemia/MDS during induction, reinduction or consolidation chemotherapy (who are expected to become neutropenic for at least 10 days) OR after allogenic HSCT with GvHD (at least grade II or more - systemic steroid treatment required)
• Need for secondary antifungal prophylaxis in patients with the history of a proven or probable invasive fungal infection who are expected to become neutropenic during induction, reinduction or consolidation chemotherapy
• Indication for treatment of proven\*\*, probable or possible fungal infection:
• Neutropenic patients with fever resistant to antibiotics (empirical use)
• Neutropenic patients with fever resistant to antibiotics and additive laboratory or imaging signs of IFI (preemptive use)
• Patients who failed other antifungal therapy due to intolerance or progressive infection

You may not qualify if:

• Absence of written informed consent
• Female patients who are pregnant or lactating
• Use of anidulafungin within 30 days prior to study
• Known hypersensitivity to anidulafungin
• Proven IFI with pathogen of known resistance to echinocandins (e.g. zygomycetes)
• Life expectancy less than 1 month
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.

Sponsors & Collaborators

• Elisabethinen Hospital: lead
• Pfizer: collaborator

Study Sites (1)

Elisabethinen hospital

Linz, Upper Austria, 4020, Austria

Location

Related Publications (7)

• Damle BD, Dowell JA, Walsky RL, Weber GL, Stogniew M, Inskeep PB. In vitro and in vivo studies to characterize the clearance mechanism and potential cytochrome P450 interactions of anidulafungin. Antimicrob Agents Chemother. 2009 Mar;53(3):1149-56. doi: 10.1128/AAC.01279-08. Epub 2008 Nov 24.

  PMID: 19029327 BACKGROUND

• Krause DS, Reinhardt J, Vazquez JA, Reboli A, Goldstein BP, Wible M, Henkel T; Anidulafungin Invasive Candidiasis Study Group. Phase 2, randomized, dose-ranging study evaluating the safety and efficacy of anidulafungin in invasive candidiasis and candidemia. Antimicrob Agents Chemother. 2004 Jun;48(6):2021-4. doi: 10.1128/AAC.48.6.2021-2024.2004.

  PMID: 15155194 BACKGROUND

• Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, Filler SG, Fisher JF, Kullberg BJ, Ostrosky-Zeichner L, Reboli AC, Rex JH, Walsh TJ, Sobel JD; Infectious Diseases Society of America. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009 Mar 1;48(5):503-35. doi: 10.1086/596757.

  PMID: 19191635 BACKGROUND

• Reboli AC, Rotstein C, Pappas PG, Chapman SW, Kett DH, Kumar D, Betts R, Wible M, Goldstein BP, Schranz J, Krause DS, Walsh TJ; Anidulafungin Study Group. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med. 2007 Jun 14;356(24):2472-82. doi: 10.1056/NEJMoa066906.

  PMID: 17568028 BACKGROUND

• De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, Pappas PG, Maertens J, Lortholary O, Kauffman CA, Denning DW, Patterson TF, Maschmeyer G, Bille J, Dismukes WE, Herbrecht R, Hope WW, Kibbler CC, Kullberg BJ, Marr KA, Munoz P, Odds FC, Perfect JR, Restrepo A, Ruhnke M, Segal BH, Sobel JD, Sorrell TC, Viscoli C, Wingard JR, Zaoutis T, Bennett JE; European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008 Jun 15;46(12):1813-21. doi: 10.1086/588660.

  PMID: 18462102 BACKGROUND

• Segal BH, Herbrecht R, Stevens DA, Ostrosky-Zeichner L, Sobel J, Viscoli C, Walsh TJ, Maertens J, Patterson TF, Perfect JR, Dupont B, Wingard JR, Calandra T, Kauffman CA, Graybill JR, Baden LR, Pappas PG, Bennett JE, Kontoyiannis DP, Cordonnier C, Viviani MA, Bille J, Almyroudis NG, Wheat LJ, Graninger W, Bow EJ, Holland SM, Kullberg BJ, Dismukes WE, De Pauw BE. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria. Clin Infect Dis. 2008 Sep 1;47(5):674-83. doi: 10.1086/590566.

  PMID: 18637757 BACKGROUND

• Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.

  PMID: 7165009 BACKGROUND

MeSH Terms

Conditions

Hematologic Neoplasms; Candidiasis, Invasive; Invasive Fungal Infections

Interventions

Anidulafungin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Candidiasis; Mycoses; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Echinocandins; Peptides, Cyclic; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Michael Girschikofsky, MD

  Elisabethinen hospital Linz GmbH

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: OA Dr. Michael Girschikofsky

Study Record Dates

• First Submitted: January 15, 2010
• First Posted: January 22, 2010
• Study Start: October 1, 2009
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: March 2, 2012

Record last verified: 2009-07

Locations

AU (1)