Caspofungin Acetate, Fluconazole, or Voriconazole in Preventing Fungal Infections in Patients Following Donor Stem Cell Transplant

• Sponsor: Children's Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT01503515
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 292
• Locations: 49
• Arms: 2
• Actual Duration (Months): 102.3
• Patients Per Site: 6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This randomized phase III trial studies how well caspofungin acetate works compared to fluconazole or voriconazole in preventing fungal infections in patients following donor stem cell transplant. Caspofungin acetate, fluconazole, and voriconazole may be effective in preventing fungal infections in patients following donor stem cell transplant. It is not yet known whether caspofungin acetate is more effective than fluconazole or voriconazole in preventing fungal infections in patients following donor stem cell transplant.

Condition or Disease	Intervention/Treatment	Phase
Fungal Infection; Hematopoietic and Lymphoid Cell Neoplasm	Drug: Caspofungin Acetate; Drug: Fluconazole; Other: Laboratory Biomarker Analysis; Drug: Voriconazole	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

1. To determine if caspofungin (caspofungin acetate) is associated with a lower incidence of proven/probable invasive fungal infections (IFI) during the first 42 days following allogeneic hematopoietic cell transplantation (HCT) at high-risk for IFI compared with azole (fluconazole or voriconazole) prophylaxis.

EXPLORATORY OBJECTIVES:

1. To determine if caspofungin is associated with a lower incidence of proven/probable IFI during the first 100 days following high-risk allogeneic HCT compared with azole (fluconazole or voriconazole) prophylaxis. (Exploratory) II. To determine if caspofungin is associated with a lower incidence of proven/probable IFI during the first 42 and 100 days following high-risk allogeneic HCT compared with fluconazole prophylaxis. (Exploratory) III. To determine if caspofungin is associated with a lower incidence of proven/probable IFI during the first 42 and 100 days following high-risk allogeneic HCT compared with voriconazole prophylaxis. (Exploratory) IV. To determine if caspofungin is associated with a superior fungal-free survival (FFS) (time to death or proven/probable IFI) at 42 and 100 days following high-risk allogeneic HCT compared with azole prophylaxis. (Exploratory) V. To describe the effect that caspofungin and azoles have on the incidence and severity of acute graft-versus-host disease (GVHD). (Exploratory) VI. To define the test characteristics of weekly Fungitell assay testing for identifying IFI in pediatric hematopoietic stem cell transplantation (HSCT) recipients receiving antifungal prophylaxis during the post-transplant neutropenic period. (Exploratory) VII. To create a deoxyribonucleic acid (DNA) specimen bank in anticipation of the development of biology correlative studies exploring the relationship between IFI and single nucleotide polymorphisms (SNPs) of genes involved in immunity. (Exploratory)

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive caspofungin acetate intravenously (IV) over 1 hour once daily (QD) beginning within 24 hours of allogeneic HSCT (day -1 or 0) and continuing until day 42 in the absence of invasive fungal infections or disease progression.

ARM II: Patients receive fluconazole IV over 1-2 hours QD or orally (PO) QD; or voriconazole IV over 1-2 hours QD or PO twice daily (BID) beginning within 24 hours of allogeneic HSCT (day -1 or 0) and continuing until day 42 in the absence of invasive fungal infections or disease progression.

After completion of study treatment, patients are followed up until day 100.

Study Design

• Study Type: Interventional
• Actual Enrollment: 292 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: A Phase III Open-Label Trial of Caspofungin vs. Azole Prophylaxis for Patients at High-Risk for Invasive Fungal Infections (IFI) Following Allogeneic Hematopoietic Cell Transplantation (HCT)
• Actual Study Start Date: Mar 21, 2013
• Actual Primary Completion Date: Dec 31, 2019
• Actual Study Completion Date: Sep 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (caspofungin acetate) Patients receive caspofungin acetate IV over 1 hour once daily (QD) beginning within 24 hours of allogeneic HSCT (day -1 or 0) and continuing until day 42 in the absence of invasive fungal infections or disease progression.	Drug: Caspofungin Acetate; Given IV; Other Names: Cancidas ; Other: Laboratory Biomarker Analysis; Optional correlative studies
Active Comparator: Arm II (fluconazole or voriconazole) Patients receive fluconazole IV over 1-2 hours QD or PO QD; or voriconazole IV over 1-2 hours QD or PO BID beginning within 24 hours of allogeneic HSCT (day -1 or 0) and continuing until day 42 in the absence of invasive fungal infections or disease progression.	Drug: Fluconazole; Given IV or PO; Other Names: Diflucan ; Other: Laboratory Biomarker Analysis; Optional correlative studies; Drug: Voriconazole; Given IV or PO; Other Names: Vfend

Outcome Measures

Primary Outcome Measures

1. 42-day-cumulative Incidence of Proven or Probable Invasive Fungal Infections (IFI) [Up to 42 days following allogeneic HCT]

   Kaplan-Meier curves will be used to estimate the 42- day-cumulative incidence of proven/probable IFI following allogeneic HCT for patients randomized to the 2 arms. Proven or probable IFI is defined according to criteria developed by the European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group (MSG).

Other Outcome Measures

1. 100-day-cumulative Incidence of Proven or Probable IFI [Up to day 100 following allogeneic HCT]

   Kaplan-Meier curves will be used to estimate the 100- day-cumulative incidence of proven/probable IFI following allogeneic HCT for patients randomized to the 2 arms. Proven or probable IFI is defined according to criteria developed by the European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group (MSG).

2. Fungal-free-survival [Up to 42 days following allogeneic HCT]

   Defined as time to death or proven/probable IFI during the first 42 days following allogeneic HCT.

3. Incidence of Overall Clinical GVHD Grades III and IV [Up to 100 days after allogeneic HCT]

   The percentage distribution of overall clinical grades III and IV will be estimated for each arm.

4. Incidence of Overall Clinical GVHD Grades II to IV [Up to 100 days after allogeneic HCT]

   The percentage distribution of overall clinical grades II and IV will be estimated for each arm.

5. Fungal-free-survival [Up to 100 days following allogeneic HCT]

   Defined as time to death or proven/probable IFI during the first 100 days following allogeneic HCT.

6. Sensitivity of Beta-D Glucan Assay for the Diagnosis of IFI Using Fungitell Assay [Up to day 42 following allogeneic HCT]

   Sensitivity of the beta-D glucan assay will be determined using standard formulas and EORTC/MSG criteria as the gold standard.

7. Specificity of Beta-D Glucan Assay for the Diagnosis of IFI Using Fungitell Assay [Up to day 42 following allogeneic HCT]

   Specificity of the beta-D glucan assay will be determined using standard formulas and EORTC/MSG criteria as the gold standard.

8. Positive Predictive Value of Beta-D Glucan Assay for the Diagnosis of IFI Using Fungitell Assay [Up to day 42 following allogeneic HCT]

   Positive predictive value of the beta-D glucan assay will be determined using standard formulas and EORTC/MSG criteria as the gold standard.

9. Negative Predictive Value of Beta-D Glucan Assay for the Diagnosis of IFI Using Fungitell Assay [Up to day 42 following allogeneic HCT]

   Negative predictive value of the beta-D glucan assay will be determined using standard formulas and EORTC/MSG criteria as the gold standard.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Months to 20 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age

• For centers that will use fluconazole as the antifungal comparator:

• Age >= 3 months and < 21 years

• For centers that will use voriconazole as the antifungal comparator:

• Age >= 2 years and < 21 years

• The patient must be undergoing allogeneic HCT from any donor (including matched related) with any stem cell source for any underlying condition

• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age

• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR a serum creatinine based on age/gender as follows:

• 0.4 mg/dL (1 month to < 6 months of age)

• 0.5 mg/dL (6 months to < 1 year of age)

• 0.6 mg/dL (1 to < 2 years of age)

• 0.8 mg/dL (2 to < 6 years of age)

• 1.0 mg/dL (6 to < 10 years of age)

• 1.2 mg/dL (10 to < 13 years of age)

• 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)

• 1.7 mg/dL (male) or 1.4 mg/dL (female) (>= 16 years of age)

• Total bilirubin < 2.5 mg/dL unless the increase in bilirubin is attributable to Gilbert's syndrome

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 5 x upper limit of normal (ULN) for age

• All patients and/or their parents or legal guardians must sign a written informed consent

• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

• Within 90 days of enrollment:

• Patients with a proven or probable invasive mold infection are not eligible

• Patients with an incompletely treated invasive yeast infection are not eligible

• Patients with an elevated galactomannan level (>= 0.5 index) within 30 days prior to time of enrollment (if performed) must have a full evaluation for invasive aspergillosis (including a negative chest computed tomography [CT] scan) during that time period to be eligible for enrollment

• Patients receiving treatment for an IFI are not eligible

• Patients with a history of echinocandin or azole hypersensitivity are not eligible

• Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained

• Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation

• Lactating females are not eligible unless they have agreed not to breastfeed their infants

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Childrens Hospital	Phoenix	Arizona	United States	85016
2	Loma Linda University Medical Center	Loma Linda	California	United States	92354
3	Children's Hospital and Research Center at Oakland	Oakland	California	United States	94609-1809
4	Children's Hospital of Orange County	Orange	California	United States	92868
5	Lucile Packard Children's Hospital Stanford University	Palo Alto	California	United States	94304
6	Rady Children's Hospital - San Diego	San Diego	California	United States	92123
7	UCSF Medical Center-Parnassus	San Francisco	California	United States	94143
8	UCSF Medical Center-Mission Bay	San Francisco	California	United States	94158
9	Alfred I duPont Hospital for Children	Wilmington	Delaware	United States	19803
10	Nemours Children's Clinic-Jacksonville	Jacksonville	Florida	United States	32207
11	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida	United States	33701
12	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia	United States	30322
13	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
14	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
15	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
16	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
17	Norton Children's Hospital	Louisville	Kentucky	United States	40202
18	Children's Hospital New Orleans	New Orleans	Louisiana	United States	70118
19	Floating Hospital for Children at Tufts Medical Center	Boston	Massachusetts	United States	02111
20	C S Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
21	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
22	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
23	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota	United States	55455
24	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905
25	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
26	Children's Mercy Hospitals and Clinics	Kansas City	Missouri	United States	64108
27	Children's Hospital and Medical Center of Omaha	Omaha	Nebraska	United States	68114
28	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
29	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
30	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467
31	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
32	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
33	Duke University Medical Center	Durham	North Carolina	United States	27710
34	Children's Hospital Medical Center of Akron	Akron	Ohio	United States	44308
35	Rainbow Babies and Childrens Hospital	Cleveland	Ohio	United States	44106
36	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
37	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
38	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
39	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
40	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
41	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
42	Medical City Dallas Hospital	Dallas	Texas	United States	75230
43	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
44	Methodist Children's Hospital of South Texas	San Antonio	Texas	United States	78229
45	Primary Children's Hospital	Salt Lake City	Utah	United States	84113
46	Children's Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53226
47	Alberta Children's Hospital	Calgary	Alberta	Canada	T3B 6A8
48	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
49	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8

Sponsors and Collaborators

• Children's Oncology Group
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Christopher C Dvorak, Children's Oncology Group

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Nov 16, 2015

More Information

Publications

None provided.

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT01503515
• Other Study ID Numbers: ACCL1131; NCI-2012-00102; CDR0000721415; ACCL1131; COG-ACCL1131; ACCL1131; U10CA095861; UG1CA189955
• First Posted: Jan 4, 2012
• Last Update Posted: Jan 31, 2022
• Last Verified: Jan 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Infections; Communicable Diseases; Mycoses; Fluconazole; Voriconazole; Caspofungin

Study Results

Participant Flow

Arm/Group Title	Arm I (Caspofungin Acetate)	Arm II (Fluconazole or Voriconazole)
Arm/Group Description	Patients receive caspofungin acetate IV over 1 hour once daily (QD) beginning within 24 hours of allogeneic HSCT (day -1 or 0) and continuing until day 42 in the absence of invasive fungal infections or disease progression. Caspofungin Acetate: Given IV Laboratory Biomarker Analysis: Optional correlative studies	Patients receive fluconazole IV over 1-2 hours QD or PO QD; or voriconazole IV over 1-2 hours QD or PO BID beginning within 24 hours of allogeneic HSCT (day -1 or 0) and continuing until day 42 in the absence of invasive fungal infections or disease progression. Fluconazole: Given IV or PO Laboratory Biomarker Analysis: Optional correlative studies Voriconazole: Given IV or PO
Period Title: Overall Study
STARTED	145	147
COMPLETED	124	112
NOT COMPLETED	21	35

Baseline Characteristics

Arm/Group Title	Arm I (Caspofungin Acetate)	Arm II (Fluconazole or Voriconazole)	Total
Arm/Group Description	Patients receive caspofungin acetate IV over 1 hour once daily (QD) beginning within 24 hours of allogeneic HSCT (day -1 or 0) and continuing until day 42 in the absence of invasive fungal infections or disease progression. Caspofungin Acetate: Given IV Laboratory Biomarker Analysis: Optional correlative studies	Patients receive fluconazole IV over 1-2 hours QD or PO QD; or voriconazole IV over 1-2 hours QD or PO BID beginning within 24 hours of allogeneic HSCT (day -1 or 0) and continuing until day 42 in the absence of invasive fungal infections or disease progression. Fluconazole: Given IV or PO Laboratory Biomarker Analysis: Optional correlative studies Voriconazole: Given IV or PO	Total of all reporting groups
Overall Participants	145	147	292
Age (Count of Participants)
<=18 years	134 92.4%	133 90.5%	267 91.4%
Between 18 and 65 years	11 7.6%	14 9.5%	25 8.6%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.2 (5.7)	9.1 (6.0)	9.2 (5.8)
Sex: Female, Male (Count of Participants)
Female	56 38.6%	56 38.1%	112 38.4%
Male	89 61.4%	91 61.9%	180 61.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	26 17.9%	27 18.4%	53 18.2%
Not Hispanic or Latino	113 77.9%	107 72.8%	220 75.3%
Unknown or Not Reported	6 4.1%	13 8.8%	19 6.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.7%	2 1.4%	3 1%
Asian	9 6.2%	6 4.1%	15 5.1%
Native Hawaiian or Other Pacific Islander	1 0.7%	0 0%	1 0.3%
Black or African American	11 7.6%	22 15%	33 11.3%
White	110 75.9%	97 66%	207 70.9%
More than one race	2 1.4%	0 0%	2 0.7%
Unknown or Not Reported	11 7.6%	20 13.6%	31 10.6%
Region of Enrollment (participants) [Number]
United States	136 93.8%	132 89.8%	268 91.8%
Canada	9 6.2%	15 10.2%	24 8.2%

Outcome Measures

1. Primary Outcome

Title	42-day-cumulative Incidence of Proven or Probable Invasive Fungal Infections (IFI)
Description	Kaplan-Meier curves will be used to estimate the 42- day-cumulative incidence of proven/probable IFI following allogeneic HCT for patients randomized to the 2 arms. Proven or probable IFI is defined according to criteria developed by the European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group (MSG).
Time Frame	Up to 42 days following allogeneic HCT

Outcome Measure Data

Analysis Population Description

study enrolled 292 patients (145 randomized to caspofungin and 147 randomized to an azole) . Two patients (1 caspofungin, 1 azole) were ineligible, resulting in 290 patients (144 caspofungin, 146 azole) included in the analysis.

Arm/Group Title	Arm I (Caspofungin Acetate)	Arm II (Fluconazole or Voriconazole)
Arm/Group Description	Patients receive caspofungin acetate IV over 1 hour once daily (QD) beginning within 24 hours of allogeneic HSCT (day -1 or 0) and continuing until day 42 in the absence of invasive fungal infections or disease progression. Caspofungin Acetate: Given IV Laboratory Biomarker Analysis: Optional correlative studies	Patients receive fluconazole IV over 1-2 hours QD or PO QD; or voriconazole IV over 1-2 hours QD or PO BID beginning within 24 hours of allogeneic HSCT (day -1 or 0) and continuing until day 42 in the absence of invasive fungal infections or disease progression. Fluconazole: Given IV or PO Laboratory Biomarker Analysis: Optional correlative studies Voriconazole: Given IV or PO
Measure Participants	144	146
Number (95% Confidence Interval) [percentage of patients]	1.4	1.4

2. Other Pre-specified Outcome

Title	100-day-cumulative Incidence of Proven or Probable IFI
Description	Kaplan-Meier curves will be used to estimate the 100- day-cumulative incidence of proven/probable IFI following allogeneic HCT for patients randomized to the 2 arms. Proven or probable IFI is defined according to criteria developed by the European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group (MSG).
Time Frame	Up to day 100 following allogeneic HCT

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Other Pre-specified Outcome

Title	Fungal-free-survival
Description	Defined as time to death or proven/probable IFI during the first 42 days following allogeneic HCT.
Time Frame	Up to 42 days following allogeneic HCT

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Other Pre-specified Outcome

Title	Incidence of Overall Clinical GVHD Grades III and IV
Description	The percentage distribution of overall clinical grades III and IV will be estimated for each arm.
Time Frame	Up to 100 days after allogeneic HCT

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Other Pre-specified Outcome

Title	Incidence of Overall Clinical GVHD Grades II to IV
Description	The percentage distribution of overall clinical grades II and IV will be estimated for each arm.
Time Frame	Up to 100 days after allogeneic HCT

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Other Pre-specified Outcome

Title	Fungal-free-survival
Description	Defined as time to death or proven/probable IFI during the first 100 days following allogeneic HCT.
Time Frame	Up to 100 days following allogeneic HCT

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	Sensitivity of Beta-D Glucan Assay for the Diagnosis of IFI Using Fungitell Assay
Description	Sensitivity of the beta-D glucan assay will be determined using standard formulas and EORTC/MSG criteria as the gold standard.
Time Frame	Up to day 42 following allogeneic HCT

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Other Pre-specified Outcome

Title	Specificity of Beta-D Glucan Assay for the Diagnosis of IFI Using Fungitell Assay
Description	Specificity of the beta-D glucan assay will be determined using standard formulas and EORTC/MSG criteria as the gold standard.
Time Frame	Up to day 42 following allogeneic HCT

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Other Pre-specified Outcome

Title	Positive Predictive Value of Beta-D Glucan Assay for the Diagnosis of IFI Using Fungitell Assay
Description	Positive predictive value of the beta-D glucan assay will be determined using standard formulas and EORTC/MSG criteria as the gold standard.
Time Frame	Up to day 42 following allogeneic HCT

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Other Pre-specified Outcome

Title	Negative Predictive Value of Beta-D Glucan Assay for the Diagnosis of IFI Using Fungitell Assay
Description	Negative predictive value of the beta-D glucan assay will be determined using standard formulas and EORTC/MSG criteria as the gold standard.
Time Frame	Up to day 42 following allogeneic HCT

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Collected Adverse Events within the 100 day observation period
Adverse Event Reporting Description	Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.
Arm/Group Title	Arm I (Caspofungin Acetate)		Arm II (Fluconazole or Voriconazole)
Arm/Group Description	Patients receive caspofungin acetate IV over 1 hour once daily (QD) beginning within 24 hours of allogeneic HSCT (day -1 or 0) and continuing until day 42 in the absence of invasive fungal infections or disease progression. Caspofungin Acetate: Given IV Laboratory Biomarker Analysis: Optional correlative studies		Patients receive fluconazole IV over 1-2 hours QD or PO QD; or voriconazole IV over 1-2 hours QD or PO BID beginning within 24 hours of allogeneic HSCT (day -1 or 0) and continuing until day 42 in the absence of invasive fungal infections or disease progression. Fluconazole: Given IV or PO Laboratory Biomarker Analysis: Optional correlative studies Voriconazole: Given IV or PO
All Cause Mortality
	Arm I (Caspofungin Acetate)		Arm II (Fluconazole or Voriconazole)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/144 (6.3%)		10/146 (6.8%)
Serious Adverse Events
	Arm I (Caspofungin Acetate)		Arm II (Fluconazole or Voriconazole)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/144 (2.8%)		3/146 (2.1%)
General disorders
Death NOS	0/144 (0%)		1/146 (0.7%)
Multi-organ failure	1/144 (0.7%)		0/146 (0%)
Infections and infestations
Infections and infestations - Other, specify	1/144 (0.7%)		0/146 (0%)
Sepsis	1/144 (0.7%)		1/146 (0.7%)
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	0/144 (0%)		1/146 (0.7%)
Respiratory failure	1/144 (0.7%)		0/146 (0%)
Other (Not Including Serious) Adverse Events
	Arm I (Caspofungin Acetate)		Arm II (Fluconazole or Voriconazole)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/144 (20.1%)		30/146 (20.5%)
Blood and lymphatic system disorders
Bone marrow hypocellular	1/144 (0.7%)		0/146 (0%)
Cardiac disorders
Pericardial effusion	1/144 (0.7%)		0/146 (0%)
Gastrointestinal disorders
Ascites	1/144 (0.7%)		0/146 (0%)
Diarrhea	1/144 (0.7%)		0/146 (0%)
Gastric hemorrhage	1/144 (0.7%)		0/146 (0%)
Gastrointestinal disorders - Other, specify	0/144 (0%)		1/146 (0.7%)
Mucositis oral	2/144 (1.4%)		1/146 (0.7%)
General disorders
Multi-organ failure	1/144 (0.7%)		0/146 (0%)
Hepatobiliary disorders
Hepatobiliary disorders - Other, specify	0/144 (0%)		1/146 (0.7%)
Portal hypertension	1/144 (0.7%)		0/146 (0%)
Infections and infestations
Device related infection	1/144 (0.7%)		0/146 (0%)
Infections and infestations - Other, specify	0/144 (0%)		1/146 (0.7%)
Lung infection	1/144 (0.7%)		2/146 (1.4%)
Peritoneal infection	1/144 (0.7%)		0/146 (0%)
Sepsis	3/144 (2.1%)		2/146 (1.4%)
Investigations
Alanine aminotransferase increased	5/144 (3.5%)		5/146 (3.4%)
Aspartate aminotransferase increased	3/144 (2.1%)		5/146 (3.4%)
Blood bilirubin increased	3/144 (2.1%)		0/146 (0%)
GGT increased	4/144 (2.8%)		0/146 (0%)
Lymphocyte count decreased	0/144 (0%)		1/146 (0.7%)
Neutrophil count decreased	0/144 (0%)		1/146 (0.7%)
Platelet count decreased	0/144 (0%)		1/146 (0.7%)
Urine output decreased	1/144 (0.7%)		0/146 (0%)
White blood cell decreased	0/144 (0%)		1/146 (0.7%)
Metabolism and nutrition disorders
Dehydration	1/144 (0.7%)		0/146 (0%)
Hypercalcemia	0/144 (0%)		2/146 (1.4%)
Hyperglycemia	1/144 (0.7%)		1/146 (0.7%)
Hyperkalemia	0/144 (0%)		1/146 (0.7%)
Hypernatremia	0/144 (0%)		1/146 (0.7%)
Hypokalemia	3/144 (2.1%)		1/146 (0.7%)
Nervous system disorders
Reversible posterior leukoencephalopathy syndrome	1/144 (0.7%)		0/146 (0%)
Renal and urinary disorders
Acute kidney injury	4/144 (2.8%)		1/146 (0.7%)
Renal and urinary disorders - Other, specify	0/144 (0%)		1/146 (0.7%)
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	1/144 (0.7%)		0/146 (0%)
Apnea	0/144 (0%)		1/146 (0.7%)
Atelectasis	1/144 (0.7%)		0/146 (0%)
Bronchopulmonary hemorrhage	1/144 (0.7%)		1/146 (0.7%)
Hypoxia	0/144 (0%)		2/146 (1.4%)
Pleural effusion	1/144 (0.7%)		2/146 (1.4%)
Pneumonitis	0/144 (0%)		1/146 (0.7%)
Pulmonary edema	1/144 (0.7%)		1/146 (0.7%)
Respiratory failure	7/144 (4.9%)		7/146 (4.8%)
Respiratory, thoracic and mediastinal disorders - Other, specify	1/144 (0.7%)		1/146 (0.7%)
Stridor	0/144 (0%)		2/146 (1.4%)
Vascular disorders
Hypertension	0/144 (0%)		1/146 (0.7%)
Hypotension	0/144 (0%)		1/146 (0.7%)
Thromboembolic event	0/144 (0%)		1/146 (0.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Must obtain prior sponsor approval.