ProphyALL - Study on the Safety of Liposomal Amphotericin B to Prevent Antifungal Infections in Elderly Patients With Acute Lymphoblastic Leukemia - Full Text View

Sponsor:	Gilead Sciences
Information provided by:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT00386997

Purpose

Due to the poor outcome of patients with invasive fungal infections (IFI), a more effective prevention of these infections in such patients is wanted. These experiences in intensively treated elderly patients with acute leukemia are especially worrying.

This pilot study is designed to collect information on the safety (and efficacy) of an antifungal preventative therapy with an AmBisome® loading dose regimen of 7 mg/kg/week, in four weekly administrations, during the aplastic phase following the start of chemotherapy for acute lymphoblastic leukemia in elderly patients, which is a high risk period for severe fungal infections.

Condition	Intervention	Phase
Fungal Infection	Drug: liposomal amphotericin B (AmBisome®)	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	ProphyALL - Pilot Study on Safety of Four Weekly Administrations of 7 mg/kg of Liposomal Amphotericin B (AmBisome®) in Antifungal Primary Prophylaxis Treatment of Elderly Patients With Acute Lymphoblastic Leukemia Undergoing Induction Chemotherapy Within the GMALL-Elderly Protocol

Resource links provided by NLM:

MedlinePlus related topics: Acute Lymphocytic Leukemia Chronic Lymphocytic Leukemia Fungal Infections Leukemia Molds

Drug Information available for: Amphotericin B

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:

To characterize the safety profile of a prophylactic antifungal LAMB treatment of
7 mg/kg, administered as a weekly intravenous infusion over two hours, during
induction treatment of acute lymphoblastic leukemia of elderly patients undergoing
chemotherapy with GMALL-Elderly 1/2003 protocol for four weeks

Secondary Outcome Measures:

Incidence and time to onset of possible, probable or proven IFI according to EORTC-MSG {3391} criteria within the 12 weeks following the initiation of prophylaxis treatment
IFI free time as % of follow-up time
The incidence of pulmonary infiltrates within 12 weeks following initiation of prophylaxis
The need for additional systemic antifungal therapy within 12 weeks following initiation of prophylaxis
The survival rate and incidence of mortality related to fungal infection at the end of prophylaxis treatment and within 12 weeks after prophylaxis treatment initiation

Estimated Enrollment:	20
Study Start Date:	November 2006
Estimated Study Completion Date:	September 2007

Detailed Description:

This is a multi-center, pilot, prospective, open label study. Approximately 20 patients will be recruited in 10 to 15 centers.

The patient group will be the following:

Elderly patients (≥ 55 years) with acute lymphoblastic leukemia undergoing chemotherapy with GMALL-Elderly 1/2003 protocol.

They will be treated with LAMB for four weeks after induction phase I. Patients will attend for full assessment until trial completion or withdrawal: there will be 3 assessment visits during the first week, 2 assessment visits during the second week, and 1 weekly assessment visit during the third and fourth week of the prophylaxis treatment (the first visit of each week being the infusion visit as well).

After the end of the prophylaxis period, patients will have 3 follow-up visits which will be scheduled at Weeks 6, 9, and 12.

Please note that no other systemic antifungal prophylaxis is allowed to be used concomitantly with AmBisome®.

Eligibility

Ages Eligible for Study:	55 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female patients
Patients with acute lymphoblastic leukemia (ALL) undergoing first induction chemotherapy within the GMALL-Elderly 1/2003 protocol
Females of childbearing potential (less than 2 years post-menopausal) must be surgically incapable of pregnancy, or practicing an acceptable method of birth control with a negative pregnancy test (blood or urine) at baseline
Understanding of the study's rationale and procedures documented in the patient's informed consent
Ability and agreement to comply with all study requirements
Patient willing to attend hospital appointments for each visit (infusions will be performed in hospital, under strict medical supervision).

Exclusion Criteria:

Known hypersensitivity to amphotericin B or LAMB or any of its constituents, in particular known history of anaphylactic reaction to amphotericin B or LAMB or any of its constituents
Signs or symptoms of IFI or previous proven or probable IFI in the medical history
Evidence for pulmonary infiltrates in chest CT and/or x-ray of the chest (only when a chest CT/x-ray is done at baseline)
Estimated creatinine clearance (ECC) ≤ 60 mL/min (Cockcroft-Gault); in such cases the body surface adjusted Modification Diet in Renal Disease (MDRD) glomerular filtration rate (GFRMDRD) should be calculated. If the body surface adjusted GFRMDRD is above 60 mL/min, the patient can be included.
Patient with moderate or severe liver disease as defined by AST, ALT or alkaline phosphatase (AP) > 5 times the upper limit of normal (ULN), or bilirubin > 3 times ULN
Patients who are unlikely to survive more than 1 month
Febrile patients (≥ 38.5°C)
Patients who have received systemic antifungal therapy within 15 days prior to the inclusion
Any severe co-morbidity other than the underlying hematological disease (ALL), which in the investigator's judgment may interfere with study evaluations or affect the patient's safety
Patients previously included in this study
Patients who have taken any investigational drug within the last 30 days prior to inclusion except drugs used according to the GMALL-Elderly/2003 protocol
Patients who participate in another clinical trial except anti-cancer trials

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00386997

Locations

Germany
Gilead Sciences GmbH
Martinsried/Munich, Germany, 82152

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Director:

Mark Sampson

Gilead Sciences GmbH

More Information

No publications provided

ClinicalTrials.gov Identifier:	NCT00386997 History of Changes
Other Study ID Numbers:	GS-MC-131-0165
Study First Received:	October 10, 2006
Last Updated:	August 20, 2007
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:

Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Mycoses
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

Amphotericin B
Liposomal amphotericin B
Antifungal Agents
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on February 09, 2012