Caspofungin Acetate in Treating Children With Fever and Neutropenia

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

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.

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.

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)