Clinical trial NCT00020527: Caspofungin Acetate in Treating Children With Fever and Neutropenia
Official title: A Multicenter, Open, Non-Comparative, Sequential Dose-Escalation Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Two Separate Doses of MK-0991 in Children With New Onset Fever and Neutropenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Fever, Sweats, and Hot Flashes
Infection
Kidney Cancer
Leukemia
Lymphoma
Neuroblastoma
Neutropenia
Sarcoma
Keywords: recurrent childhood acute lymphoblastic leukemia
recurrent childhood rhabdomyosarcoma
disseminated neuroblastoma
recurrent neuroblastoma
recurrent Wilms tumor and other childhood kidney tumors
recurrent childhood lymphoblastic lymphoma
recurrent childhood acute myeloid leukemia
fever, sweats, and hot flashes
childhood acute promyelocytic leukemia (M3)
recurrent/refractory childhood Hodgkin lymphoma
neutropenia
infection
recurrent childhood small noncleaved cell lymphoma
recurrent childhood large cell lymphoma
previously treated childhood rhabdomyosarcoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Primary purpose: SUPPORTIVE_CARE

Brief summary: RATIONALE: Giving caspofungin acetate may be effective in preventing or controlling fever and neutropenia caused by chemotherapy or bone marrow transplantation.

PURPOSE: Clinical trial to study the effectiveness of caspofungin acetate in treating children who have fever and neutropenia caused by a weakened immune system.

Detailed description: OBJECTIVES:

* Determine the pharmacokinetics and serum levels of caspofungin acetate in immunocompromised children with new-onset fever and neutropenia.
* Determine the safety and tolerability of this drug in this patient population.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to age (2 to 11 vs 12 to 17).

Patients receive caspofungin acetate IV over 1 hour once daily for 4 to 28 days in the absence of the need to start standard empirical antifungal therapy, a breakthrough fungal infection, any deterioration of patient condition, or unacceptable toxicity.

Cohorts of 16 patients (8 per stratum) receive caspofungin acetate at 1 of 2 dose levels. Caspofungin acetate is escalated to dose level 2 if no more than 1 of 8 patients experiences dose-limiting toxicity at dose level 1.

Patients are followed at 14 days.

PROJECTED ACCRUAL: A total of 32-64 patients (16 per dose level (cohort), 8 per stratum) will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Immunocompromised with one or more of the following conditions:

  * Leukemia, lymphoma, or other cancer
  * Underwent bone marrow or peripheral blood stem cell transplantation
  * Aplastic anemia
* Planned chemotherapy likely to incur more than 10 days of neutropenia
* Absolute neutrophil count no greater than 500/mm\^3 AND at least 1 recorded fever over 38.0 ° C within 24 hours of study
* No proven invasive fungal infection at time of study entry

  * Superficial fungal infection (e.g., cutaneous fungal infection, thrush, or candidal vaginitis) treatable with topical antifungals allowed

PATIENT CHARACTERISTICS:

Age:

* 2 to 17

Performance status:

* Not specified

Life expectancy:

* At least 5 days

Hematopoietic:

* See Disease Characteristics
* Hemodynamically stable with no hemodynamic compromise

Hepatic:

* AST or ALT no greater than 3 times upper limit of normal (ULN)
* Alkaline phosphatase no greater than 5 times ULN (unless related to bony metastases or other suspected bony processes)
* INR no greater than 1.6 (4.0 if receiving anticoagulants)
* No acute hepatitis or cirrhosis

Renal:

* Not specified

Other:

* Functioning central venous catheter in place
* No other condition or concurrent illness that would preclude study
* No prior allergy, hypersensitivity, or serious reaction to echinocandin antifungals
* HIV negative
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception other than or in addition to oral contraceptives

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* See Disease Characteristics

Chemotherapy:

* See Disease Characteristics

Endocrine therapy:

* Not specified

Radiotherapy:

* Not specified

Surgery:

* Not specified

Other:

* No prior enrollment into this study
* No more than 48 hours since prior parenteral systemic antibacterial therapy for fever and neutropenia
* At least 14 days since prior investigational antibiotic or antifungal drugs
* Concurrent topical antifungals (i.e., nystatin and/or azole formulations) for a superficial fungal infection allowed
* No other concurrent investigational drugs, including antibiotics or antifungals
* No concurrent rifampin, cyclosporine, phenytoin, carbamazapine, phenobarbital, or other antifungal treatments (except fluconazole)

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Washington
country: United States
facility: Lombardi Cancer Center
state: District of Columbia
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
state: Maryland
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: National Cancer Institute (NCI)
name: Thomas J. Walsh, MD
role: STUDY_CHAIR
References: