Invasive AspergillosisPhase 4NCT00334412
COMBISTRAT: AmBisome® in Combination With Caspofungin for the Treatment of Invasive Aspergillosis
A Phase 4 study testing Ambisome and caspofungin in people with Invasive Aspergillosis, run by Gilead Sciences at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 10 years and older
- Conditions the study is for
- Invasive Aspergillosis
- What is being tested?
- Ambisome and caspofungin
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- Mar 2004to May 2006
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: AmBisome® in Combination With Caspofungin Versus AmBisome® High Dose Regimen for the Treatment of Invasive Aspergillosis in Immunocompromized Patients: Randomized Pilot Study.
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.
Read the detailed description
Efficacy and toxicity of caspofungin in combination with AmBisome® as primary or salvage treatment of invasive aspergillosis has already been assessed in patients with hematologic malignancies. Forty-eight patients with documented (n=23) or possible (n=25) Invasive Aspergillosis (IA). The majority of the patients (65%) received the combination as salvage therapy for progressive IA despite 7 or more days of previous AmBisome monotherapy. The overall response rate was 42%. No significant toxic effects were seen. Factors associated with failure at the end of therapy were documented IA (P=0.03), significant steroid use before the study (P=0.02), and duration of combination therapy for less than 14 days (P=0.01). The response rate in patients with progressive documented IA was low (18%). Authors' concluded that combination is a promising therapy for IA and was generally well tolerated.35 Furthermore interaction of caspofungin and amphotericin B for clinical isolates of Aspergillus and Fusarium was assessed. Antagonism was not observed for any of the isolates tested. Caspofungin and amphotericin B were synergistic or synergistic to additive for at least half of the isolates studied.36 Gentina et al. evaluated, in refractory IA, i.v. antifungal therapies combining caspofungin (70 mg on D1, followed by 50 mg/d) with Vfend® (200 mg b.i.d) or AmBisome (5 mg/kg/d). Six leukaemia patients with refractory IA received combination including caspofungin with AmBisome (n = 4) or Vfend (n = 2). Combination therapies were started 8 days after initial IA diagnosis. Duration of neutropenia after initiation of combination therapy ranged 4 to 25 days. IA was classified as definite in 3 cases and probable in 3 cases. All patients had pulmonary IA, including one with disseminated IA (cerebral, thyroid, ocular and pulmonary). In all patients, sequential CT-scans demonstrated improvement with a rapid reduction of the size of lesions. Additional surgery was only required in 2 cases. Improvement allowed administration of consolidation chemotherapy in 3 patients without recurrence of IA. Median duration of combination therapy was 62 days (range 42-107). No toxicity related to this combination antifungal therapy was observed.37 The combination therapy of caspofungin and amphotericin (or liposomal amphotericin) was also assessed by Aliff et al. in a retrospective evaluation of a group of 30 patients with amphotericin-resistant pulmonary aspergillosis and other invasive fungal infections. Twenty-six patients had acute leukemia. Diagnosis was based on clinical, radiographic, and when available, microbiologic data. Response to combination antifungal therapy was graded as either favorable or unfavorable. Favorable responses included improvement of both clinical and radiographic signs of fungal pneumonia. All other responses were graded as unfavorable. Based on the EORTC criteria, the IFIs were classified as proven in 6 patients, probable in 4 patients, and possible in 20 patients. The median duration and dose of amphotericin monotherapy were 12 days (range, 4-65 days) and 7.8 mg/kg (range, 4.2-66.1 mg/kg),respectively. The median duration of combination therapy was 24 days (range, 3-74 days). Eighteen patients (60%) experienced a favorable antifungal response. Twenty patients with acute leukemia received combination therapy for fungal pneumonias arising during intensive chemotherapy treatments. Favorable responses were observed in 15 of these patients (75%), and antifungal response did not depend on the response of the underlying leukemia. Survival to hospital discharge was significantly better (P < 0.001) in patients having a favorable response. Authors concluded that the combination of caspofungin and amphotericin B can be administered safely to high-risk patients with hematologic malignancies.38 Combination therapy 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.
- Conditions
- Invasive Aspergillosis
- Being tested
- Ambisome, caspofungin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmbisomeDrug
caspofunginDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess efficacy of AmBisome® in combination with caspofungin (Cancidas®) versus AmBisome® high dose regimen in the treatment of Invasive Aspergillosis diagnosed by modified EORTC criteria in immunocompromised patients as probable or proven and deter
Secondary outcomes (5)
To evaluate and compare the safety and tolerability of the two arms.
To determine the survival rates and rates of infection relapse at 4 weeks post-treatment for patients treated with each of the two treatment regimens.
To determine the survival rate at 12 weeks after study entry for patients treated with each of the two treatment regimens.
To determine and compare the time to favorable response and time to maximal overall response for each of the two treatment regimens.
To compare the efficacy of each arm versus historical data on conventional amphotericin B and voriconazole for the treatment of Invasive Aspergillosis.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2006 (estimated)
- Study startMar 2004
- Study completionMay 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Invasive AspergillosisStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Lamine Mahi, MD, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00334412
- Sponsor's protocol ID
- GS-FR-131-0106
- Status last verified
- Jul 2015
- First submitted
- 5 Jun 2006
- Last updated
- 9 Jul 2015
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AmBisome® in Combination With Caspofungin Versus AmBisome® High Dose Regimen for the Treatment of Invasive Aspergillosis in Immunocompromized Patients: Randomized Pilot Study.
- ClinicalTrials.gov ID
- NCT00334412
- Acronym / sponsor ID
- GS-FR-131-0106
- Conditions
- Invasive Aspergillosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- Mar 2004
- Study completion
- May 2006
- First posted
- 7 Jun 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Efficacy and toxicity of caspofungin in combination with AmBisome® as primary or salvage treatment of invasive aspergillosis has already been assessed in patients with hematologic malignancies. Forty-eight patients with documented (n=23) or possible (n=25) Invasive Aspergillosis (IA). The majority of the patients (65%) received the combination as salvage therapy for progressive IA despite 7 or more days of previous AmBisome monotherapy. The overall response rate was 42%. No significant toxic effects were seen. Factors associated with failure at the end of therapy were documented IA (P=0.03), significant steroid use before the study (P=0.02), and duration of combination therapy for less than 14 days (P=0.01). The response rate in patients with progressive documented IA was low (18%). Authors' concluded that combination is a promising therapy for IA and was generally well tolerated.35 Furthermore interaction of caspofungin and amphotericin B for clinical isolates of Aspergillus and Fusarium was assessed. Antagonism was not observed for any of the isolates tested. Caspofungin and amphotericin B were synergistic or synergistic to additive for at least half of the isolates studied.36 Gentina et al. evaluated, in refractory IA, i.v. antifungal therapies combining caspofungin (70 mg on D1, followed by 50 mg/d) with Vfend® (200 mg b.i.d) or AmBisome (5 mg/kg/d). Six leukaemia patients with refractory IA received combination including caspofungin with AmBisome (n = 4) or Vfend (n = 2). Combination therapies were started 8 days after initial IA diagnosis. Duration of neutropenia after initiation of combination therapy ranged 4 to 25 days. IA was classified as definite in 3 cases and probable in 3 cases. All patients had pulmonary IA, including one with disseminated IA (cerebral, thyroid, ocular and pulmonary). In all patients, sequential CT-scans demonstrated improvement with a rapid reduction of the size of lesions. Additional surgery was only required in 2 cases. Improvement allowed administration of consolidation chemotherapy in 3 patients without recurrence of IA. Median duration of combination therapy was 62 days (range 42-107). No toxicity related to this combination antifungal therapy was observed.37 The combination therapy of caspofungin and amphotericin (or liposomal amphotericin) was also assessed by Aliff et al. in a retrospective evaluation of a group of 30 patients with amphotericin-resistant pulmonary aspergillosis and other invasive fungal infections. Twenty-six patients had acute leukemia. Diagnosis was based on clinical, radiographic, and when available, microbiologic data. Response to combination antifungal therapy was graded as either favorable or unfavorable. Favorable responses included improvement of both clinical and radiographic signs of fungal pneumonia. All other responses were graded as unfavorable. Based on the EORTC criteria, the IFIs were classified as proven in 6 patients, probable in 4 patients, and possible in 20 patients. The median duration and dose of amphotericin monotherapy were 12 days (range, 4-65 days) and 7.8 mg/kg (range, 4.2-66.1 mg/kg),respectively. The median duration of combination therapy was 24 days (range, 3-74 days). Eighteen patients (60%) experienced a favorable antifungal response. Twenty patients with acute leukemia received combination therapy for fungal pneumonias arising during intensive chemotherapy treatments. Favorable responses were observed in 15 of these patients (75%), and antifungal response did not depend on the response of the underlying leukemia. Survival to hospital discharge was significantly better (P < 0.001) in patients having a favorable response. Authors concluded that the combination of caspofungin and amphotericin B can be administered safely to high-risk patients with hematologic malignancies.38 Combination therapy 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ambisome | Drug | – |
| caspofungin | Drug | – |
Primary outcome
To assess efficacy of AmBisome® in combination with caspofungin (Cancidas®) versus AmBisome® high dose regimen in the treatment of Invasive Aspergillosis diagnosed by modified EORTC criteria in immunocompromised patients as probable or proven and deter
5 secondary outcomes
To evaluate and compare the safety and tolerability of the two arms.
To determine the survival rates and rates of infection relapse at 4 weeks post-treatment for patients treated with each of the two treatment regimens.
To determine the survival rate at 12 weeks after study entry for patients treated with each of the two treatment regimens.
To determine and compare the time to favorable response and time to maximal overall response for each of the two treatment regimens.
To compare the efficacy of each arm versus historical data on conventional amphotericin B and voriconazole for the treatment of Invasive Aspergillosis.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lamine Mahi, MD study director
Gilead Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ambisome and caspofungin in people with Invasive Aspergillosis, run by Gilead Sciences at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess efficacy of AmBisome® in combination with caspofungin (Cancidas®) versus AmBisome® high dose regimen in the treatment of Invasive Aspergillosis diagnosed by modified EORTC criteria in immunocompromised patients as probable or proven and deter. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2015.