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

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.

Study Overview

• Status: Terminated
• Conditions: Hematologic Neoplasms
• Intervention / Treatment: Drug: Itraconazole; Drug: Caspofungin

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijign, China
  • Beijing, China
  • Changchun, China
  • Changzhou, China
  • Fuzhou, China
  • Guangzhou, China
  • Guiyang, China
  • Hefei, China
  • Shanghai, China
  • Suzhou, China
  • Tianjin, China
  • Zhengzhou, China

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant must be hospitalized with hematologic malignancy treated by myelosuppressive therapy and/or Hematopoietic stem cell transplantation
• Participant must have a diagnosis of neutropenia with neutrophil count < 500/microliters (mcL) (0.5 × 10^9/ liters [L]) for at least 96 hours at screening
• Participant must have a diagnosis of fever and meet the following criteria: 1) Oral/rectal temperature greater than or equal to (>=) 38 degree celsius or axillary temperature (>=) 37.5 degree celsius and is not considered related to blood products transfusion or drug fever, 2) Not responding to broad-spectrum gram-positive and gram-negative antibiotics for 4-7 days with or without signs and symptoms that potentially attributable to deep fungal infection and 3) Defervescence within 3 days after the first broad-spectrum antibiotics but recurrence afterwards.
• A woman of childbearing potential must have a negative serum (beta human chorionic gonadotropin [b hCG]) and pregnancy test at screening
• A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study period and until the menstrual period following the end of study treatment

Exclusion Criteria:

• Is concomitantly using other systematic antifungal drugs as empirical treatment
• Has evidence of inadequately managed bacterial infection
• Is currently receiving any Cytochrome P450 3A4 (CYP3A4)-metabolized/P-glycoprotein-transported drugs (including but not limited to cisapride, pimozide, quinidine, dofetilide, levacetylmethadol, terfenadine, astemizole, mizolastine, bepridil, sertindole, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase) inhibitor [for example, simvastatin, lovastatin], oral midazolam, triazolam, ergot alkaloids [eg, dihydroergotamine, ergonovine, ergotamine, methylergonovine] and nisoldipine) that should be prohibited in this study
• Has known allergy, intolerance or hypersensitivity to azole and echinocandin antifungals or its excipients
• Has a contraindication to the use of sodium chloride injection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Itraconazole	Drug: Itraconazole; 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.
Active Comparator: Caspofungin	Drug: Caspofungin; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate Measured by the Percentage of Participants That Achieve all of the Following 5 Composite Endpoints	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.	Up to 36 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Survival for 7 Days After Completion of Treatment		Up to 36 days
Percentage of Participants With Absence of Breakthrough Invasive Fungal Infection	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.	Day 3 up to Day 28 (End of treatment [EoT]) and within 7 days after EoT (Day 29 up to Day 35)
Percentage of Participants With Successful Treatment of Baseline Fungal Infection	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.	Screening up to Day 3
Percentage of Participants With Defervescence During the Period of Neutropenia	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.	Up to 36 days
Percentage of Participants With No Premature Withdrawal From the Study due to Drug-related Toxicity or Lack of Efficacy		Up to 36 days
Response Rate Measured by the Percentage of Participants That Achieve all of the Following 5 Composite Endpoints With Oral Administration of Itraconazole	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.	Up to 36 days

Collaborators and Investigators

• Sponsor: Xian-Janssen Pharmaceutical Ltd.

Publications and helpful links

Helpful Links

• 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

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2016
• Primary Completion (Actual): May 2, 2018
• Study Completion (Actual): May 2, 2018

Study Registration Dates

• First Submitted: September 6, 2016
• First Submitted That Met QC Criteria: September 6, 2016
• First Posted (Estimate): September 9, 2016

Study Record Updates

• Last Update Posted (Actual): May 6, 2019
• Last Update Submitted That Met QC Criteria: May 2, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Caspofungin; Itraconazole
• Other Study ID Numbers: CR108202; R051211FUN4057 (Other Identifier: Xian-Janssen Pharmaceutical Ltd., China)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No