Voriconazole in Preventing or Treating Fungal Infections in Younger Patients Undergoing Stem Cell Transplant

Status: Closed to Accrual and Intervention

Description

This phase I trial studies the best dose of voriconazole in preventing or treating fungal infections in younger patients undergoing stem cell transplant. Infection is a serious risk of a transplant because the body’s usual defenses (the immune system and associated blood cell counts) are severely suppressed (weakened). Voriconazole may help prevent or treat fungal infections in patients undergoing stem cell transplant.

Eligibility Criteria

Inclusion Criteria

  • Any patient undergoing allogeneic hematopoietic stem cell transplantation (either 1st or subsequent)
  • Creatinine < 1.5 x upper limit of normal (ULN) OR
  • Glomerular filtration rate (GFR) of >= 50 mL/min/1.73 m^2
  • Alanine aminotransferase (ALT), aspartate aminotransferase (AST) < 3 x ULN
  • Total bilirubin < 3 x ULN
  • Requires voriconazole to prevent or treat invasive fungal infection (IFI) post HSCT
  • Voluntary written consent

Exclusion Criteria

  • Has received voriconazole within 5 days prior to starting study therapy
  • History of hypersensitivity or severe intolerance to azoles
  • Current evidence of cardiac arrhythmias defined as corrected QD interval (QTc) >= 480 mm/sec
  • Receiving one of the following drugs and cannot be discontinued at least 24 hours before starting therapy, including: pimozide, quinidine, astemizole, ergot alkaloids
  • Received one or more of the following drugs within 14 days prior to starting study: rifampin, rifabutin, carbamazepine, phenytoin, nevirapine, long-acting barbiturates
  • Received sirolimus within the 14 days prior to starting study as voriconazole is a potent inhibitor of sirolimus metabolism
  • Receiving or anticipated need for methadone as co-administration with voriconazole potentially increases methadone exposure

Locations & Contacts

See trial information on ClinicalTrials.gov for a list of participating sites.

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated, minimum efficacious dose (MTD, MED) of voriconazole for different pediatric age groups undergoing bone marrow transplantation, specifically what starting voriconazole dose correlates with a concentration in the therapeutic range for each age group without excessive toxicity.

SECONDARY OBJECTIVES:

I. How the initial dose correlates with voriconazole concentration for each age group.

II. To determine what voriconazole dose correlates with elevations to 5 times the upper limit of normal in liver enzymes.

III. To estimate incidence of fungal infection within 6 months post-transplant.

TERTIARY OBJECTIVES:

I. To characterize the effect of genetic polymorphisms within family 2, subfamily C, polypeptide 19 (2C19), flavin mono-oxygenase-3 (FMO-3), and NAD(P)H dehydrogenase, quinone 1 (NQO1) on voriconazole and voriconazole N-oxide pharmacokinetic variability in pediatric patients receiving allogeneic hematopoietic stem cell transplant (HSCT).

II. To characterize the effect of patient specific characteristics including age, gender, primary disease, hepatic function, creatinine clearance and concomitant medications on voriconazole and voriconazole N-oxide pharmacokinetic variability in pediatric patients receiving allogeneic HSCT.

OUTLINE: This is a dose-escalation study.

Patients receive voriconazole intravenously (IV) or orally (PO) every 12 hours on days 1-30 after HSCT. Patients may continue voriconazole as medically appropriate independent of this study.

After completion of study treatment, patients are followed up for 1 week.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Supportive care

Lead Organization

Lead Organization
University of Minnesota / Masonic Cancer Center

Principal Investigator
Angela Renee Smith

Trial IDs

Primary ID 2013LS126
Secondary IDs NCI-2015-00535, MT2013-37R
Clinicaltrials.gov ID NCT02227797