MDACC Study Summary 2007-0188 (Archived)

Study Summary
No. 2007-0188:.......Infection......Dimitrios P. Kontoyiannis......Infectious Disease

Study Summary Title



Study Summary Number:	2007-0188

Study Title:	Deferasirox-Ambisome Therapy for Mucormycosis (DEFEAT Mucor) Phase II Study Protocol : Version 2.2

Physician

New Patient Referral



Name:	Dimitrios P. Kontoyiannis	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Infectious Disease	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-6237 Contact us about clinical trials

General Information



Disease Group:	Infection	Supported By:	Astellas Gilead Los Angeles Biomedical Research Institute at Harbor -UCLA Medical Center. Novartis

Phase of Study:	Phase II	Return Visit:	Once monthly for 3 months.

Treatment Agents:	Amphotericin B Lipid Complex Deferasirox	Home Care:	None.

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

Estimated Length of Stay in Houston:	The patient will be admitted if necessary. The study can be conducted on an outpatient basis.


Description/ Intervention:	The goal of this clinical research study is to test the safety of deferasirox in patients with fungal infections. The effectiveness of deferasirox will also be tested.

Study Objectives / Outcomes

Primary Objective:
The primary objective is to determine the safety and tolerability of adjunctive deferasirox therapy in
patients being treated with LAmB for mucormycosis, and to obtain exploratory data on the efficacy of the iron chelation treatment. The primary safety endpoint will be assessed by defining the frequency, type, and severity of adverse events during the on-therapy period. The exploratory efficacy endpoint will be the global response rate (composite of clinical and radiographic response) at end of study drug administration, as determined by a blinded adjudication committee.

Secondary Objectives:
1. To compare the frequency, type, and severity of adverse effects during the first week of study medication administration versus during the second week of study medication administration in subjects receiving deferasirox or placebo.
2. To determine serum deferasirox levels at study day 7 in patients with mucormycosis.
3. To compare serum deferasirox levels in subjects with or without intestinal graft versus host disease.
4. To compare ferritin, total iron binding capacity, total serum iron, and Labile Plasma Iron levels at baseline, and at study days 7, 14, and 30 in subjects receiving deferasirox versus placebo, and to compare changes over time within each group.
5. To determine the relationship between serum deferasirox and LPI levels.
6. To determine deferasirox and LPI concentrations in any surgical or biopsy specimens obtained while on therapy, with concomitant serum deferasirox and LPI levels.
7. To compare transplant immunosuppressive medication levels in patients taking deferasirox vs. placebo.
8. To compare all-cause and mucormycosis-attributable mortality at end of study drug administration, day 30 and 90 in patients taking deferasirox vs. placebo.
9. To compare time to all-cause and mucormycosis-attributable death up to study day 90 by Kaplan-Meier curves in patients taking deferasirox vs. placebo.
10. To compare the global response at end of study therapy.
11. To compare the global response in the study arms at study day 30 and 90 in patients taking deferasirox vs. placebo.
12. To compare separately the clinical or radiographic response rates at the end of study drug administration, and at study days 30 and 90 in patients taking deferasirox vs. placebo.
13. To determine the deferasirox and LAmB Minimum Inhibitory and Minimum Fungicidal Concentrations of clinical isolates of Mucorales cultured from patients.
14. To determine the impact of subject variables, including demographics, predisposing conditions, LAmB dose, receipt of posaconazole or echinocandins prior to enrollment, baseline iron studies, changes in iron studies from baseline to end of therapy, or LAmB MICs or MFCs, on success or failure at the end of study drug administration.

Study Status Information



Study Activation / Registration Date:	12/10/2007

IRB Review and Approval Date:	12/10/2007

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Terminated

Projected Accrual:	20

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Age > or equal to 2 years.

2) Proven or probable invasive mucormycosis, as defined by modification of consensus European Organization for Research and Treatment of Cancer (EORTC)/Mycosis Study Group (MSG) criteria.

3) Proven mucormycosis is defined as: 1) histopathologic or cytopathologic examination showing broad-based, aseptate, ribbon-like hyphae consistent with Mucorales from needle aspiration or biopsy specimen, with evidence of associated tissue damage (either microscopically or unequivocally by imaging); OR 2) a positive culture result for a sample obtained by sterile procedure from normally sterile and clinically or radiologically abnormal site consistent with infection, excluding urine and mucous membranes.

4) (Cont from # 3): 1) an at-risk host; AND 2) positive culture, cytology, or polymerase chain reaction (PCR) test (run at a CLIA-certified clinical microbiology laboratory) from sputum, bronchoalveolar lavage (BAL), endoscoscopy/colonoscopy, or sinus aspirate/biopsy; AND 3) 1 major or 2 minor clinical criteria

5) Radiographic study by Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) has been obtained within 4 calendar days prior to enrollment and shows evidence of infection (i.e. focal nodule, mass, or abscess, or enhancement, or evidence of tissue edema or destruction that is not attributed to post-surgical reaction).

6) Subject or authorized decision maker able to provide informed consent.

Exclusion Criteria:

1) High likelihood of death within the 48 h after enrollment (investigator's discretion).

2) High likelihood of death due to factors unrelated to mucormycosis (e.g. due to uncontrolled and/or relapsed malignancy, severe graft versus host disease, other underlying diseases, etc.) within 30 days following enrollment (investigator's discretion).

3) Patient unable to receive enteral medication (oral or via feeding tube).

4) Infection limited to the supra-fascial skin (skin lesions in the presence of disseminated disease, deep invasive tissue infection spreading from a primary skin site, or subcutaneous infections extending to fascia are allowed).

5) Patient has received > 14 days of polyene antifungal therapy (i.e. amphotericin B deoxycholate, liposomal amphotericin B, amphotericin B lipid complex, or amphotericin B colloidal dispersion) at the time of screening.

6) Patient is already taking deferasirox therapy for any reason at the time of screening

7) Patient is allergic to or intolerant of deferasirox or LAmB.

8) Patient has significant renal dysfunction at the time of screening, defined as serum creatinine of >/= 3 mg/dL or a calculated creatinine clearance of < 30 ml/min (by the Cockroft-Gault formula: (140 – age (yrs) * wt (kg) * 0.85 (for females) / (72 * serum creatinine (mg/dL).

9) Patient has significant hepatic dysfunction at the time of screening, defined as BOTH an AST or ALT > 10 times the upper limit of normal, AND a direct (not total) bilirubin > 5 times the upper limit of normal.

10) Women of child-bearing potential (those with menses within the last year) with a positive serum pregnancy test.

11) Enrollment refused by the primary physician.

Links

Registration Number: NCT00419770
Study Information on Clinical Trials Registry (clinicaltrials.gov)