COMBISTRAT: AmBisome® in Combination With Caspofungin for the Treatment of Invasive Aspergillosis

• Status: Completed
• Trial end date: 2006-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Combination therapy of caspofungin and amphotericin B could be a useful treatment option in invasive fungal disease, but before it can be routinely recommended; carefully controlled and well-designed randomized clinical trials are needed.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gilead Sciences
• Treatments: Amphotericin B; Caspofungin; Echinocandins; Liposomal amphotericin B

Criteria

Inclusion Criteria:

• Adults and children > 10 years old.

• The patient is able to understand and has signed a written informed consent OR the parent or legal guardian is able to understand and has signed a written informed consent, which must be obtain prior to the initiation of any study procedures.

• Immunocompromised due to hematologic malignancies, chemotherapy-induced neutropenia, solid organ transplantation, other conditions resulting in severe neutropenia, HIV infection, prolonged corticosteroid therapy (≥ 20 mg Prednisone or equivalent for ≥ 3 weeks) or treatment with other immunosuppressant medications.

• Evidence of Proven or Probable Invasive Aspergillosis, by modified EORTC criteria (Appendix 2), as modified below: • Proven Invasive Aspergillosis • Histopathologic or cytopathologic examination showing hyphae consistent with the presence of aspergillus from needle aspiration or biopsy specimen with evidence of associated tissue damage (either microscopically or unequivocally by imaging); or • Positive culture result for aspergillosis from a sample obtained by sterile procedure from normally sterile and clinically or radiologically abnormal site consistent with infection, excluding urine and mucous membranes • Probable Invasive Aspergillosis • At least 1 host factor criterion; and • 1 microbiological criterion; and

• 1 major (or 2 minor) clinical criteria from abnormal site consistent with infection; and • No other pathogens detected to account for the clinical or radiographic signs of infection

• Or (Modification of EORTC Criteria): • Patients with recent Neutropenia (absolute neutrophil count < 500 cells/mm3 within 14 days of study enrollment); and • Chest CT scan positive for "Halo" or "Air Crescent" Sign (see Section 4.2.1, Diagnostic Considerations, below) and • No other pathogens detected to account for the clinical or radiographic signs of infection

• Females of childbearing potential must be surgically incapable of pregnancy, or practicing an acceptable method of birth control with a negative pregnancy test (blood or urine) at baseline.

Exclusion Criteria:

Life expectancy < 30 days

• Allogenic stem cell transplant in the 6 previous months

• Chronic invasive fungal infection, defined as signs/symptoms of invasive fungal infection present for > 4 weeks preceding entry into study

• Prior anti-fungal systemic therapy of ≥ 96 hours for the current, documented IA. (On the other hand, is permissible prior systemic anti-fungal therapy for prophylaxis or as empiric therapy for febrile neutropenia).

• Use of another investigational, unlicensed drug within 30 days of screening or concurrent participation in another clinical trial using an investigational, unlicensed drug • Serum creatinine > 2x upper limit of normal (ULN)

• Serum ALT or AST > 5 x ULN

• Pregnant or lactating women

• History of allergy or serious adverse reaction to any polyene anti-fungal agent or echinochandin derivatives