Incidence of Invasive Fungal Disease in Patients receiving Immunosuppressive Therapy, Intensive Chemotherapy or Reduced Intensity Haematopoietic Stem Cell Transplantation on Posaconazole tablet Prophylaxis

• Register: EUCTR
• Last refreshed on: 25 May 2020
• Main ID: EUCTR2016-001223-31-GB
• Date of registration: 07/09/2016
• Prospective Registration: Yes
• Primary sponsor: King's College Hospital NHS Foundation Trust
• Public title: Incidence of Invasive Fungal Disease in Patients receiving Immunosuppressive Therapy, Intensive Chemotherapy or Reduced Intensity Haematopoietic Stem Cell Transplantation on Posaconazole tablet Prophylaxis
• Scientific title: Incidence of Invasive Fungal Disease in Patients receiving Immunosuppressive Therapy, Intensive Chemotherapy or Reduced Intensity Haematopoietic Stem Cell Transplantation on Posaconazole Prophylaxis - King's Invasive Aspergillosis Study II (KIASII)
• Date of first enrolment: 11/10/2016
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001223-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

United Kingdom

Contacts

• Name: Professor Antonio Pagliuca
• Affiliation: King's College Hospital NHS Foundation Trust

• Name: Professor Antonio Pagliuca
• Affiliation: King's College Hospital NHS Foundation Trust

Key inclusion & exclusion criteria

Inclusion criteria:
1. Adult > or = to 18 years
2. Patients with aplastic anaemia, MDS or AML undergoing: IST; or Intensive chemotherapy such as induction chemotherapy; or RIC allogeneic HSCT
3. Able to swallow and retain orally administered medication
4.Patients must agree to use and apply with effective contraception without interruption throughout the duration of study drug therapy
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150

Exclusion criteria:
1. Refusal or inability to consent
2. Autologous HSCT
3. Contraindicated medications
4. Current evidence of IFD diagnosis or treatment
5.Women who are pregnant or lactating


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Aplastic Anaemia, Myelodysplastic syndromes, Acute Myeloid Leukaemia undergoing immunosuppression therapy, high dose chemotherapy or reduced intensity stem cell transplantation
MedDRA version: 19.0 Level: LLT Classification code 10038271 Term: Refractory anaemia with excess blasts in transformation System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 19.0 Level: LLT Classification code 10059041 Term: Allogeneic peripheral haematopoietic stem cell transplant System Organ Class: 10042613 - Surgical and medical procedures
MedDRA version: 19.0 Level: LLT Classification code 10067862 Term: Allogeneic stem cell transplantation System Organ Class: 10042613 - Surgical and medical procedures
MedDRA version: 19.0 Level: PT Classification code 10038270 Term: Refractory anaemia with an excess of blasts System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 19.0 Level: LLT Classification code 10010776 Term: Constitutional aplastic anaemia System Organ Class: 10005329 - Blood and lymphatic system disorders
MedDRA version: 19.0 Level: LLT Classification code 10068063 Term: Aplastic anaemia relapse System Organ Class: 10005329 - Blood and lymphatic system disorders
MedDRA version: 19.0 Level: LLT Classification code 10036699 Term: Primary idiopathic aplastic anaemia System Organ Class: 10005329 - Blood and lymphatic system disorders
MedDRA version: 19.0 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 19.0 Level: PT Classification code 10001756 Term: Allogenic bone marrow transplantation therapy System Organ Class: 10042613 - Surgical and medical procedures
MedDRA version: 19.0 Level: LLT Classification code 10000884 Term: Acute myeloid leukaemia NOS System Organ Class: 10029104 -

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Trade Name: Noxafil®
Product Name: Noxafil Gastro resistant tablets
Pharmaceutical Form: Tablet

Primary Outcome(s)

Main Objective: To determine the cumulative incidence of invasive fungal disease (IFD) in patients given posaconazole tablet as primary prophylaxis at the start of admission for immunosuppressive therapy, chemotherapy or allogeneic RIC HSCT.

Primary end point(s): Cumulative incidence of IFD in all treatment groups (aplastic anaemia with IST, chemotherapy only, RIC allograft) assessed over 24 weeks from Day 1 of study entry

Timepoint(s) of evaluation of this end point: Between day 1 and week 24

Secondary Objective: SECONDARY 1. To determine the cumulative incidence of IFD within treatment groups.
2. To measure trough plasma levels of posaconazole and correlate with the incidence of IFD
3. To determine the number of patients who received antifungal treatment
4. To determine if calcineurin inhibitors such as cyclosporine A or tacrolimus adversely affect the plasma posaconazole levels
5. To determine the clinical response to antifungal therapy
6. To determine the clinical performance of ß-D-glucan, galactomannan, bi (methylthio)gliotoxin and PCR diagnostic tests
7. To assess the risk factors (e.g. baseline CT abnormalities, baseline ILR2 and MCP1 levels, GVHD, prolonged monocytopenia, poor performance status) for IFD

EXPLORATORY 1. To determine IFD incidence, number of patients on antifungal prophylaxis and treatment beyond week 24 of the study 2. To determine overall survival 3.To determine the pharmaco-economics of IFD diagnosis and treatment

Secondary Outcome(s)

Secondary end point(s): 1.Cumulative incidence of IFD within treatment groups (aplastic anaemia with IST, chemotherapy only, RIC allograft) assessed over 24 weeks from Day 1 of study entry
2.Trough plasma levels of posaconazole correlated with the incidence of IFD assessed over 24 weeks from Day 1 of study entry
3.The number of patients who received antifungal treatment assessed over 24 weeks from Day 1 of study entry
4.Whether calcineurin inhibitors such as cyclosporine A or tacrolimus adversely affect plasma posaconazole levels assessed over 24 weeks from Day 1 of study entry
5.Clinical response to antifungal therapy assessed over 24 weeks from Day 1 of study entry
6.Clinical performance of GM, BDG, bmGT and PCR assessed over 24 weeks from Day 1 of study entry
7.The risk factors (baseline CT abnormalities, baseline IL2R and MCP1 levels, GVHD, prolonged monocytopenia, poor performance status) for IFD assessed over 24 weeks from Day 1 of study entry
Exploratory Endpoints
1.IFD incidence, number of patients on antifungal prophylaxis and treatment from 24 weeks until 12 months
2.Overall survival at 6, 9 and 12 months
3.Pharmaco-economics of IFD diagnosis and treatment assessed over 12 months

Timepoint(s) of evaluation of this end point: Secondary endpoints assessed between day 1 and week 24
Exploratory endpoints assessed at 12 months

Secondary ID(s)

KAISII

Source(s) of Monetary Support

Merck Sharp & Dohme Limited (MSD).

Ethics review

Status: Approved
Approval date: 11/10/2016
Contact: