Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03014934 |
| Other study ID # |
EBMT-8414113 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 2016 |
| Est. completion date |
December 2021 |
Study information
| Verified date |
January 2021 |
| Source |
European Group for Blood and Marrow Transplantation |
| Contact |
Jennifer Hoek, MD |
| Phone |
+31715265668 |
| Email |
j.d.c.hoek[@]lumc.nl |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Via a prospective non-interventional study clinical outcome of patients with - and without -
history of pre-existing invasive aspergillosis undergoing allo-HSCT will be assessed, in
terms of non-relapse mortality overall mortality and fungal infectious morbidity.
Aim. Assessment of 1-year outcome of patients undergoing allo-HSCT with history of
pre-existing IA vs. no pre-existing IA.
Hypothesis. NRM in patients with pre-existing IA is not higher (by a specified margin of 10%)
than patients without pre-existing IA.
Study population. First allo-HSCT in patients with acute leukaemia and MDS given stem cell
grafts.
Cohort 1: History of probable or proven invasive aspergillosis Cohort 2: No History of
probable or proven invasive aspergillosis: this cohort includes also the patient with a
history of possible mycosis not documented microbiologically.
Description:
Background & Rationale. In patients with pre-existing invasive aspergillosis allo-HSCT is
feasible without progression of fungal infection. However, the influence of invasive
pulmonary aspergillosis (IA) on transplant related complications and on long term survival
has not been investigated in a larger patient cohort under current conditions.
Recently the IDWP and ALWP performed a retrospective analysis on the impact of preexisting
aspergillosis on allo-HSCT outcome.2 In summary, there was a trend towards impaired outcome
of allo-HSCT in patients with prior IA but there was no significant impact on important
allo-HSCT transplant outcomes, such as survival, GVHD and relapse. The data suggest that a
history of IA should not generally be considered a contraindication for allo-HSCT. To be able
to more precisely investigate the impact of IA on allo-HSCT, a non-interventional prospective
study is needed.
Primary objective:
To determine if pre-existing IA influences non-relapse mortality after allo-HSCT
Secondary objectives:
- To determine if pre-existing IA influences:
- relapse free survival
- overall survival
- incidence and severity of GVHD
- incidence of relapse
- incidence of IA post allo-HSCT
for the subgroup of transplant with previous IA
• progression of IA
Research design:
Prospective study. Study recruitment is expected to start by May 1st, 2016. It is expected
that recruitment will be closed by October 31st 2017. Follow up will be till one year after
transplant.
Items:
Data from Med A form, Med C form for all patients, Aspergillus form for patients with
probable/proven IA.
Endpoint(s):
Primary endpoint: 1-year non-relapse mortality cumulative incidence
Secondary endpoints:
- 1-year relapse free survival
- 1-year overall survival
- 1-year incidence and severity of GVHD
- 1-year incidence of relapse
- status of IA (before conditioning and at 1 year)
Study population
- First allo-HSCT in patients with AML or
- First allo-HSCT in patients with ALL or
- First allo-HSCT in patients with MDS
Cohort 1: History of probable or proven invasive aspergillosis Cohort 2: No History of
probable or proven invasive aspergillosis
Cases: Prior IA = probable/proven IA according EORTC 2008 criteria (Cohort 1) Controls: No
prior proven probable IA = all other patients = those really negative for IA and those with
possible IA (Cohort 2)
Sample size Assuming a 20% incidence of non relapse mortality in patients without proven or
probable history of IA, a total of 2100 HSCTs will be needed in order to test the hypothesis
that the incidence of non relapse mortality in cohort 1 (HSCTs with previous history of
proven or probable IA) is not higher than cohort 2 (HSCTs without history of IA or with
previous history of possible IA) by more than a specified margin of 10%. The estimated
proportion of HSCTs in cohort 1 is 5%, thus 105 and 1995 HSCTs will be needed in cohort 1 and
cohort 2, respectively, considering an alpha=0.05, a beta=0.2.
Data Collection & Statistical Analysis Plan:
(List all research variables to be collected and list all outcome variables to be analysed,
give a brief description of the method of analysis (in collaboration with the EBMT
statistician) All data collection will be performed by the IDWP Data Office (Leiden)
according to EBMT guidelines.
Primary endpoint: non relapse mortality The non relapse mortality will be estimated using the
cumulative incidence method. Death due to transplant will be considered as an event, whilst
relapse of the underlying disease will be considered as competing events. Patients alive at
the end of the follow-up will be censored at this date. Cohort 1, vs. Cohort 2 will be
compared by the Gray test.
A cause specific Cox model will be performed in order to estimate the risk of dying for
Cohort 1 respect Cohort 2.
The following variables will enter the multivariate model as possible confounders: age (as
continuous variable), gender (M vs. F), underlying disease (ALL vs. AML/MDS), status at SCT
(1st CR vs. ≥ 2 CR vs. Prim Refr/noCR), time from diagnosis to SCT (as continuous variable),
donor type (sibling vs. UD vs. Haplo), source of SCT (BM vs. PB vs. CB), donor age, d/r
gender match, d/r CMV status, conditioning regimens (MAC vs. RIC vs. TBI), type of
immunosuppression (in vivo T depletion y/n, in vitro T-depletion y/n), DLI post SCT (y/n),
centre.
Secondary endpoints Relapse free survival and overall survival will be estimated by the
Kaplan-Meier methods. Incidence of GvHD and incidence of relapse will be estimated by the
cumulative incidence methods. A cause specific Cox model will be estimated to compare Cohort
1 and Cohort 2; it will be adjusted by the confounders analyzed also in the primary endpoint.
The severity of GvHD will be described by descriptive statistics. Frequencies and percentages
will be use for categorical variables, whilst median, range, mean and standard deviation will
be computed for continuous variables.
Additional descriptive statistic will be separately performed in cohort 2. Main
characteristics of patients will be also described.
