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

This study has been terminated.
(Study closed due to recruitment challenges.)
Sponsor:
Information provided by:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00386997
First received: October 10, 2006
Last updated: August 20, 2007
Last verified: August 2007
  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 4

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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
Infection
Communicable Diseases
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Mycoses
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Amphotericin B
Liposomal amphotericin B
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Bacterial Agents
Antifungal Agents

ClinicalTrials.gov processed this record on September 29, 2014