Invasive Fungal InfectionsPhase 3NCT00750737
Oral Posaconazole Three Times Per Day vs Weekly High Dose Amphotericin B Lipid Complex (ABLC)
A Phase 3 study testing Posaconazole and ABLC in people with Invasive Fungal Infections and Hematologic Malignancies, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The objective of this study is to compare the safety and efficacy of ABLC versus oral Posaconazole in the prevention of invasive fungal infections in high risk patients with hematologic malignancies or hematopoietic stem cell transplant. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Invasive Fungal Infections, Hematologic Malignancies
- What is being tested?
- Posaconazole and ABLC
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2008to Jun 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects: 18 years of age or above.
- Any allogeneic hematopoietic stem cell transplant (HSCT) patient who is at risk of invasive fungal infection (IFI) within 6 months of the transplant will be eligible for the study according to HSCT institutional anti-fungal prophylaxis guidelines.
- Subjects must be willing to give written informed consent and able to adhere to dosing and study visit schedule.
- Female subjects of childbearing potential must have a negative serum pregnancy test (beta-human chorionic gonadotropin [hCG]) at Baseline or within 96 hours before the start of study drug.
- Female subjects of childbearing potential must agree to use a medically accepted method of contraception prior to screening, while receiving protocol-specified medication, and for 30 days after stopping the medication. Acceptable methods of contraception include condoms with/without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed IUD (intrauterine device), oral/injectable hormonal contraceptive, surgical sterilization (e.g. hysterectomy/tubal ligation).
Who cannot join
- Subjects previously treated with antifungal therapy (voriconazole, fluconazole, or itraconazole) for proven or probable IFI within 30 days of enrollment.
- Subjects who have taken the following drugs: terfenadine, cisapride, primazide, and ebastine; that are known to interact with azoles and that may lead to life-threatening side effects, within 24 hours before study drug administration. And astemizole within 7 days before study drug administration.
- Subjects who have taken the following drugs: cimetidine, rifampin, carbamezapine, phenytoin, rifabutin, barbiturates, isoniazid, and vinca alkaloids (vincristine, vinblastine); that are known to lower the serum concentration/efficacy of azole antifungal agents, within 24 hours before study drug administration.
- Subjects with a history of hypersensitivity or idiosyncratic reactions to azole agents or Amphotericin B.
- Subjects on other nephrotoxic agents (e.g. foscarnet).
- Patients who are unable to take pills.
Show all 12Show fewer
- Subjects with proven or probable invasive fungal infection.
- Subjects with renal insufficiency (estimated creatine clearance less than 50mL/minute at Baseline or likely to require dialysis during the study).
- Subjects having ECG with a prolonged QTc interval by manual reading: QTc greater than 500 msec. at Baseline.
- Subjects with moderate or severe liver dysfunction at baseline, defined as aspartate amniotransferase (AST), alanine amniotransferase (ALT) and / or a total bilirubin level greater than 3 times the upper limit of normal (ULN).
- Women who are breast feeding, pregnant, or intend to become pregnant during the course of the study.
- Prior enrollment in this study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase III Clinical Trial of Oral Posaconazole 3 Times/Day vs Weekly High Dose Amphotericin B Lipid Complex (ABLC) for Prevention of Invasive Fungal Infections In Patients With Hematologic Malignancies & Hematopoietic Stem Cell Transplant
The objective of this study is to compare the safety and efficacy of ABLC versus oral Posaconazole in the prevention of invasive fungal infections in high risk patients with hematologic malignancies or hematopoietic stem cell transplant.
Primary objective is to demonstrate the low toxicity rate and low rate of invasive fungal infections associated with ABLC or Posaconazole prophylaxis.
Secondary objective will be to compare the cost effectiveness of these two prophylactic regimens.
Read the detailed description
The Study Drugs:
ABLC is an antifungal drug that is commonly used to treat and/or prevent a variety of serious invasive fungal infections (IFIs). In this study, ABLC will be used for IFI prevention.
Posaconazole is a newer antifungal drug that is commonly used to prevent serious IFIs.
Study Groups:
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to receive either posaconazole or ABLC. You will have an equal chance (50/50) of being assigned to either group. You and your study doctor will know which group you are in.
Study Drug Administration:
If you are assigned to the Posaconazole Group, you will take posaconazole 3 times a day by mouth for up to 6 weeks (Days 1-42). The study doctor will advise you about taking it with fatty meals and/or nutritional supplements.
If you are assigned to the ABLC Group, you will receive ABLC once a week by vein over 4-6 hours, for up to 6 weeks (from Day 1 through Day 42). If the creatinine level increases, the dose will be divided into 2 doses per week. The drug may be given in the hospital (if you are admitted to the hospital before or during the study) or at an outpatient treatment center.
Study Visits:
Once a week from Day 1 to Day 42, you will have the following procedures performed:
- Blood (about 1 tablespoon) will be drawn for routine tests.
- You will be asked about any medications and treatments you may be receiving.
- You will be asked about any IFI symptoms that may have developed. You will also be asked about any side effects that may have occurred since your last visit. (You should contact the study doctor and/or study staff right away, if at any time you feel you have had a side effect.)
You may have certain routine diagnostic tests performed at any time in the study, if necessary to confirm you do not have an IFI. These tests may include blood collection (about 1 tablespoon), scans, skin tissue biopsy, and/or bronchoscopy.
Length of Study:
You will receive study treatment for up to 6 weeks (42 days). If you develop an IFI or any intolerable side effects, you will be taken off study early. You may also be taken off study if your neutrophil (a type of white blood cell) counts recover.
End-of-Treatment Visit:
Your End-of-Treatment visit will be on the last day you received the study drug (at most, 42 days after you started). The following procedures will be performed.
- Blood (about 1 tablespoon) will be drawn for routine tests.
- You will have a physical exam, including measurement of vital signs.
- If the study doctor and/or your primary doctor thinks you may have an IFI, routine diagnostic tests may be performed.
Follow-up Visit:
Your follow up visit will be completed 7 - 14 days after your end-of-treatment visit. The following procedures will be performed:
- You will be checked for any signs of IFI.
- If your doctor suspects you have an IFI, a scan (such as an x-ray or CT scan) and/or bronchoscopy may be performed.
- You will be asked about any medications and treatments you may be receiving, and any side effects you may have had.
- Your vital signs will be checked, and a physical exam may be performed.
- Blood (about 1 tablespoon) will be drawn for routine tests.
- An ECG may be performed.
This is an investigational study. ABLC and posaconazole are FDA approved and commercially available for the treatment and prevention of IFIs. Posaconazole is FDA approved for the way it is being used in this study. The study dose and study schedule for ABLC, however, is considered experimental. Currently, this dose and schedule for ABLC is being used in research only.
Up to 100 patients will take part in this study. All will be enrolled at M. D. Anderson.
- Being tested
- Posaconazole, ABLC
- Keywords
- Hematologic Malignancies, Blood Cancer, Lymphatic Cancer, Amphotericin B Lipid Complex, Amphotericin B, ABLC, Fungizone, Noxafil, SCH56592, Posaconazole, Invasive fungal infections, IFI, Hematopoietic Stem Cell Transplant, HSCT, Bone Marrow Transplant, Allogeneic hematopoietic stem cell transplant
- Medical subject headings
- Invasive Fungal Infections, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PosaconazoleDrug
Also called SCH56592, Noxafil
200 mg three times daily by mouth up to 6 weeks (Days 1-42)
ABLCDrug
Also called Amphotericin B Liquid Complex, Fungizone
7.5 mg/kg of ABLC intravenously infused over 4-6 hours once per week, for up to 6 weeks (from Day 1 through Day 42)
| Study group | Role | What they receive |
|---|---|---|
| Posaconazole | Experimental | Posaconazole 200 mg three times daily by mouth up to 6 weeks (Days 1-42) Receives: Drug: Posaconazole |
| Amphotericin B Lipid Complex (ABLC) | Experimental | 7.5 mg/kg of ABLC intravenously infused over 4-6 hours once per week, for up to 6 weeks (from Day 1 through Day 42) Receives: Drug: ABLC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Invasive Fungal Infection (IFI)
Percentage of participants that developed IFI within 7 days of antifungal prophylaxis therapy (Posaconazole or ABLC).
Measured: Within 7 days of antifungal prophylaxis therapy
Secondary outcomes (1)
Efficacy Outcome Measured as Success or Failure
Success: Defined as the absence of proven or probable invasive fungal infection through the end of prophylaxis and absence of Grade 1-4 toxicity related to prophylaxis requiring the discontinuation of the drug. Failure: Presence of proven or probable fungal infection or development of Grade 1-4 toxicity related to prophylaxis while on study drug and requiring discontinuation of study drug or inability to tolerate intravenous ABLC (due to infusion related toxicities) or oral Posaconazole (due to mucositis or vomiting).
Measured: Day 1 through Day 42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2008 (estimated)
- Study startJun 2008
- Primary completionJun 2012
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Invasive Fungal InfectionsStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Enzon Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Issam Raad, MD/Professor, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00750737
- Sponsor's protocol ID
- 2007-0020
- Status last verified
- Jan 2016
- First submitted
- 10 Sep 2008
- Last updated
- 29 Sep 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Chaftari AM, Hachem RY, Ramos E, Kassis C, Campo M, Jiang Y, Prince RA, Wang W, Raad II. Comparison of posaconazole versus weekly amphotericin B lipid complex for the prevention of invasive fungal infections in hematopoietic stem-cell transplantation. Transplantation. 2012 Aug 15;94(3):302-8. doi: 10.1097/TP.0b013e3182577485.
PubMed 22814329
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Clinical Trial of Oral Posaconazole 3 Times/Day vs Weekly High Dose Amphotericin B Lipid Complex (ABLC) for Prevention of Invasive Fungal Infections In Patients With Hematologic Malignancies & Hematopoietic Stem Cell Transplant
- ClinicalTrials.gov ID
- NCT00750737
- Acronym / sponsor ID
- 2007-0020
- Keywords
- Hematologic Malignancies, Blood Cancer, Lymphatic Cancer, Amphotericin B Lipid Complex, Amphotericin B, ABLC, Fungizone, Noxafil
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Enzon Pharmaceuticals, Inc.
- Study start
- Jun 2008
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 11 Sep 2008 (estimated)
- Results
- Posted 6 Jan 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study is to compare the safety and efficacy of ABLC versus oral Posaconazole in the prevention of invasive fungal infections in high risk patients with hematologic malignancies or hematopoietic stem cell transplant.
Primary objective is to demonstrate the low toxicity rate and low rate of invasive fungal infections associated with ABLC or Posaconazole prophylaxis.
Secondary objective will be to compare the cost effectiveness of these two prophylactic regimens.
Detailed description
The Study Drugs:
ABLC is an antifungal drug that is commonly used to treat and/or prevent a variety of serious invasive fungal infections (IFIs). In this study, ABLC will be used for IFI prevention.
Posaconazole is a newer antifungal drug that is commonly used to prevent serious IFIs.
Study Groups:
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to receive either posaconazole or ABLC. You will have an equal chance (50/50) of being assigned to either group. You and your study doctor will know which group you are in.
Study Drug Administration:
If you are assigned to the Posaconazole Group, you will take posaconazole 3 times a day by mouth for up to 6 weeks (Days 1-42). The study doctor will advise you about taking it with fatty meals and/or nutritional supplements.
If you are assigned to the ABLC Group, you will receive ABLC once a week by vein over 4-6 hours, for up to 6 weeks (from Day 1 through Day 42). If the creatinine level increases, the dose will be divided into 2 doses per week. The drug may be given in the hospital (if you are admitted to the hospital before or during the study) or at an outpatient treatment center.
Study Visits:
Once a week from Day 1 to Day 42, you will have the following procedures performed:
- Blood (about 1 tablespoon) will be drawn for routine tests.
- You will be asked about any medications and treatments you may be receiving.
- You will be asked about any IFI symptoms that may have developed. You will also be asked about any side effects that may have occurred since your last visit. (You should contact the study doctor and/or study staff right away, if at any time you feel you have had a side effect.)
You may have certain routine diagnostic tests performed at any time in the study, if necessary to confirm you do not have an IFI. These tests may include blood collection (about 1 tablespoon), scans, skin tissue biopsy, and/or bronchoscopy.
Length of Study:
You will receive study treatment for up to 6 weeks (42 days). If you develop an IFI or any intolerable side effects, you will be taken off study early. You may also be taken off study if your neutrophil (a type of white blood cell) counts recover.
End-of-Treatment Visit:
Your End-of-Treatment visit will be on the last day you received the study drug (at most, 42 days after you started). The following procedures will be performed.
- Blood (about 1 tablespoon) will be drawn for routine tests.
- You will have a physical exam, including measurement of vital signs.
- If the study doctor and/or your primary doctor thinks you may have an IFI, routine diagnostic tests may be performed.
Follow-up Visit:
Your follow up visit will be completed 7 - 14 days after your end-of-treatment visit. The following procedures will be performed:
- You will be checked for any signs of IFI.
- If your doctor suspects you have an IFI, a scan (such as an x-ray or CT scan) and/or bronchoscopy may be performed.
- You will be asked about any medications and treatments you may be receiving, and any side effects you may have had.
- Your vital signs will be checked, and a physical exam may be performed.
- Blood (about 1 tablespoon) will be drawn for routine tests.
- An ECG may be performed.
This is an investigational study. ABLC and posaconazole are FDA approved and commercially available for the treatment and prevention of IFIs. Posaconazole is FDA approved for the way it is being used in this study. The study dose and study schedule for ABLC, however, is considered experimental. Currently, this dose and schedule for ABLC is being used in research only.
Up to 100 patients will take part in this study. All will be enrolled at M. D. Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Posaconazole | Experimental | Drug: PosaconazolePosaconazole 200 mg three times daily by mouth up to 6 weeks (Days 1-42) |
| Amphotericin B Lipid Complex (ABLC) | Experimental | Drug: ABLC7.5 mg/kg of ABLC intravenously infused over 4-6 hours once per week, for up to 6 weeks (from Day 1 through Day 42) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Subjects: 18 years of age or above.
- Any allogeneic hematopoietic stem cell transplant (HSCT) patient who is at risk of invasive fungal infection (IFI) within 6 months of the transplant will be eligible for the study according to HSCT institutional anti-fungal prophylaxis guidelines.
- Subjects must be willing to give written informed consent and able to adhere to dosing and study visit schedule.
- Female subjects of childbearing potential must have a negative serum pregnancy test (beta-human chorionic gonadotropin [hCG]) at Baseline or within 96 hours before the start of study drug.
- Female subjects of childbearing potential must agree to use a medically accepted method of contraception prior to screening, while receiving protocol-specified medication, and for 30 days after stopping the medication. Acceptable methods of contraception include condoms with/without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed IUD (intrauterine device), oral/injectable hormonal contraceptive, surgical sterilization (e.g. hysterectomy/tubal ligation).
Key exclusion criteria (12 listed)
- Subjects previously treated with antifungal therapy (voriconazole, fluconazole, or itraconazole) for proven or probable IFI within 30 days of enrollment.
- Subjects who have taken the following drugs: terfenadine, cisapride, primazide, and ebastine; that are known to interact with azoles and that may lead to life-threatening side effects, within 24 hours before study drug administration. And astemizole within 7 days before study drug administration.
- Subjects who have taken the following drugs: cimetidine, rifampin, carbamezapine, phenytoin, rifabutin, barbiturates, isoniazid, and vinca alkaloids (vincristine, vinblastine); that are known to lower the serum concentration/efficacy of azole antifungal agents, within 24 hours before study drug administration.
- Subjects with a history of hypersensitivity or idiosyncratic reactions to azole agents or Amphotericin B.
- Subjects on other nephrotoxic agents (e.g. foscarnet).
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 |
|---|---|---|
| PosaconazoleAlso: SCH56592, Noxafil200 mg three times daily by mouth up to 6 weeks (Days 1-42) | Drug | Posaconazole |
| ABLCAlso: Amphotericin B Liquid Complex, Fungizone7.5 mg/kg of ABLC intravenously infused over 4-6 hours once per week, for up to 6 weeks (from Day 1 through Day 42) | Drug | Amphotericin B Lipid Complex (ABLC) |
Primary outcome
Incidence of Invasive Fungal Infection (IFI)
Time frame: Within 7 days of antifungal prophylaxis therapy
Percentage of participants that developed IFI within 7 days of antifungal prophylaxis therapy (Posaconazole or ABLC).
1 secondary outcome
Efficacy Outcome Measured as Success or Failure
Time frame: Day 1 through Day 42
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22814329Chaftari AM, Hachem RY, Ramos E, Kassis C, Campo M, Jiang Y, Prince RA, Wang W, Raad II. Comparison of posaconazole versus weekly amphotericin B lipid complex for the prevention of invasive fungal infections in hematopoietic stem-cell transplantation. Transplantation. 2012 Aug 15;94(3):302-8. doi: 10.1097/TP.0b013e3182577485.
- The University of Texas MD Anderson Cancer Center Official WebsiteLink provided by the sponsor.
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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.
Issam Raad, MD/Professor principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Posaconazole and ABLC in people with Invasive Fungal Infections and Hematologic Malignancies, run by M.D. Anderson Cancer Center at 1 site in United States.
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 5 inclusion and 12 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 29 Sep 2016. 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 United States. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jan 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Incidence of Invasive Fungal Infection (IFI) (time frame: Within 7 days of antifungal prophylaxis therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00750737, which also lists 1 linked publication.
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 29 Sep 2016.