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

Condition(s) targeted: Fungal Infection; Hematopoietic/Lymphoid Cancer

Intervention: caspofungin acetate (Drug); fluconazole (Drug); voriconazole (Drug); laboratory biomarker analysis (Other)

Phase: Phase 3

Status: Recruiting

Sponsored by: Children's Oncology Group

Official(s) and/or principal investigator(s):
Christopher Dvorak, MD, Principal Investigator, Affiliation: Children's Oncology Group

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.

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)

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Primary outcome: Development of proven or probable IFI defined according to criteria developed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group

Secondary outcome:

Development of proven or probable IFI

Fungal-free-survival

Incidence of acute GVHD

Detailed description: PRIMARY OBJECTIVES: I. 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. SECONDARY OBJECTIVES: I. 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 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 hematopoietic stem cell transplantation (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.

Minimum age: 3 Months. Maximum age: 20 Years. Gender(s): Both.

Criteria:

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

Phoenix Childrens Hospital, Phoenix, Arizona 85016, United States; Recruiting
Christopher C. Dvorak, Phone: 877-827-3222
Christopher C. Dvorak, Principal Investigator

Loma Linda University Medical Center, Loma Linda, California 92354, United States; Recruiting
Antranik A. Bedros, Phone: 909-558-3375
Antranik A. Bedros, Principal Investigator

Children's Hospital and Research Center at Oakland, Oakland, California 94609-1809, United States; Recruiting
Mark C. Walters, Phone: 510-450-7600
Mark C. Walters, Principal Investigator

Childrens Hospital of Orange County, Orange, California 92868-3874, United States; Recruiting
Violet Shen, Phone: 714-997-3000
Violet Shen, Principal Investigator

Lucile Packard Children's Hospital Stanford University, Palo Alto, California 94304, United States; Recruiting
Neyssa M. Marina, Phone: 650-498-7061, Email: clinicaltrials@med.stanford.edu
Neyssa M. Marina, Principal Investigator

Rady Children's Hospital - San Diego, San Diego, California 92123, United States; Recruiting
William D. Roberts, Phone: 858-966-5934
William D. Roberts, Principal Investigator

University of California San Francisco Medical Center-Parnassus, San Francisco, California 94143, United States; Recruiting
Christopher C. Dvorak, Phone: 877-827-3222
Christopher C. Dvorak, Principal Investigator

Alfred I duPont Hospital for Children, Wilmington, Delaware 19803, United States; Recruiting
Scott M. Bradfield, Phone: 904-697-3529
Scott M. Bradfield, Principal Investigator

Nemours Children's Clinic - Jacksonville, Jacksonville, Florida 32207, United States; Recruiting
Scott M. Bradfield, Phone: 904-697-3529
Scott M. Bradfield, Principal Investigator

All Children's Hospital, Saint Petersburg, Florida 33701, United States; Recruiting
Aleksandra Petrovic, Phone: 727-767-2423, Email: HamblinF@allkids.org
Aleksandra Petrovic, Principal Investigator

Children's Healthcare of Atlanta - Egleston, Atlanta, Georgia 30322, United States; Recruiting
Ann E. Haight, Phone: 888-785-1112
Ann E. Haight, Principal Investigator

Riley Hospital for Children, Indianapolis, Indiana 46202, United States; Recruiting
Robert J. Fallon, Phone: 317-274-2552
Robert J. Fallon, Principal Investigator

Kosair Children's Hospital, Louisville, Kentucky 40202, United States; Recruiting
Alexandra C. Cheerva, Phone: 866-530-5516
Alexandra C. Cheerva, Principal Investigator

Children's Hospital-Main Campus, New Orleans, Louisiana 70118, United States; Recruiting
Lolie C. Yu, Phone: 504-894-5377
Lolie C. Yu, Principal Investigator

CancerCare Manitoba, Winnipeg, Manitoba R3E 0V9, Canada; Recruiting
Rochelle A. Yanofsky, Phone: 866-561-1026, Email: CIO_Web@cancercare.mb.ca
Rochelle A. Yanofsky, Principal Investigator

Floating Hospital for Children at Tufts Medical Center, Boston, Massachusetts 02111, United States; Recruiting
Michael J. Kelly, Phone: 617-636-5000, Email: ContactUsCancerCenter@TuftsMedicalCenter.org
Michael J. Kelly, Principal Investigator

C S Mott Children's Hospital, Ann Arbor, Michigan 48109, United States; Recruiting
John E. Levine, Phone: 800-865-1125
John E. Levine, Principal Investigator

Wayne State University/Karmanos Cancer Institute, Detroit, Michigan 48201, United States; Recruiting
Roland L. Chu, Phone: 313-576-9363
Roland L. Chu, Principal Investigator

Helen DeVos Children's Hospital at Spectrum Health, Grand Rapids, Michigan 49503, United States; Recruiting
David S. Dickens, Phone: 616-267-1925
David S. Dickens, Principal Investigator

University of Minnesota Medical Center-Fairview, Minneapolis, Minnesota 55455, United States; Recruiting
Michael R. Verneris, Phone: 612-624-2620
Michael R. Verneris, Principal Investigator

Mayo Clinic, Rochester, Minnesota 55905, United States; Recruiting
Shakila P. Khan, Phone: 507-538-7623
Shakila P. Khan, Principal Investigator

University of Mississippi Medical Center, Jackson, Mississippi 39216, United States; Recruiting
Gail C. Megason, Phone: 601-815-6700
Gail C. Megason, Principal Investigator

The Childrens Mercy Hospital, Kansas City, Missouri 64108, United States; Recruiting
Maxine L. Hetherington, Phone: 816-234-3265
Maxine L. Hetherington, Principal Investigator

Children's Hospital and Medical Center of Omaha, Omaha, Nebraska 68114, United States; Recruiting
Minnie Abromowitch, Phone: 402-955-3949
Minnie Abromowitch, Principal Investigator

University of Nebraska Medical Center, Omaha, Nebraska 68198, United States; Recruiting
Peter F. Coccia, Phone: 800-999-5465
Peter F. Coccia, Principal Investigator

Hackensack University Medical Center, Hackensack, New Jersey 07601, United States; Recruiting
Jennifer A. Krajewski, Phone: 201-996-2879
Jennifer A. Krajewski, Principal Investigator

Montefiore Medical Center - Moses Campus, Bronx, New York 10467-2490, United States; Recruiting
Peter D. Cole, Phone: 718-904-2730, Email: aecc@aecom.yu.edu
Peter D. Cole, Principal Investigator

Roswell Park Cancer Institute, Buffalo, New York 14263, United States; Recruiting
Barbara J. Bambach, Phone: 877-275-7724
Barbara J. Bambach, Principal Investigator

University of North Carolina, Chapel Hill, North Carolina 27599, United States; Recruiting
Stuart H. Gold, Phone: 877-668-0683, Email: cancerclinicaltrials@med.unc.edu
Stuart H. Gold, Principal Investigator

Duke University Medical Center, Durham, North Carolina 27710, United States; Recruiting
Susan G. Kreissman, Phone: 888-275-3853
Susan G. Kreissman, Principal Investigator

Children's Hospital Medical Center of Akron, Akron, Ohio 44308, United States; Recruiting
Steven J. Kuerbitz, Phone: 330-543-3193
Steven J. Kuerbitz, Principal Investigator

Cleveland Clinic Foundation, Cleveland, Ohio 44195, United States; Recruiting
Margaret C. Thompson, Phone: 866-223-8100
Margaret C. Thompson, Principal Investigator

Rainbow Babies and Childrens Hospital, Cleveland, Ohio 44106, United States; Recruiting
Yousif (Joe) H. Matloub, Phone: 216-844-5437
Yousif (Joe) H. Matloub, Principal Investigator

Nationwide Children's Hospital, Columbus, Ohio 43205, United States; Recruiting
Mark A. Ranalli, Phone: 614-722-2708
Mark A. Ranalli, Principal Investigator

University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, United States; Recruiting
Rene Y. McNall-Knapp, Phone: 405-271-4272, Email: julie-traylor@ouhsc.edu
Rene Y. McNall-Knapp, Principal Investigator

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States; Recruiting
David M. Barrett, Phone: 215-590-2810
David M. Barrett, Principal Investigator

Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania 15224, United States; Recruiting
Rakesh K. Goyal, Phone: 412-692-5573
Rakesh K. Goyal, Principal Investigator

Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232, United States; Recruiting
Adam Esbenshade, Phone: 800-811-8480
Adam Esbenshade, Principal Investigator

Medical City Dallas Hospital, Dallas, Texas 75230, United States; Recruiting
Carl Lenarsky, Phone: 972-566-5588
Carl Lenarsky, Principal Investigator

University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States; Recruiting
Victor M. Aquino, Phone: 214-648-7097
Victor M. Aquino, Principal Investigator

Methodist Children's Hospital of South Texas, San Antonio, Texas 78229, United States; Recruiting
Jaime Estrada, Phone: 210-575-7000
Jaime Estrada, Principal Investigator

Primary Children's Hospital, Salt Lake City, Utah 84113, United States; Recruiting
Meghann P. McManus, Phone: 423-778-7289
Meghann P. McManus, Principal Investigator

Midwest Children's Cancer Center, Milwaukee, Wisconsin 53226, United States; Recruiting
Michael E. Kelly, Phone: 414-805-4380
Michael E. Kelly, Principal Investigator

Starting date: March 2013
Last updated: August 12, 2015