The primary objective of the study is to provide natural history data onpatients with P-CID, irrespective of whether they undergo HSCT or not.The goals are to determine survival, the frequency of severe eventsand quality of life 5 years after study…
ID
Source
Brief title
Condition
- Immunodeficiency syndromes
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is overall survival determined after year 5. The
event analysed is death from any cause. The time to this event is the
time from the first major infection or major manifestation of immune
dysregulation (documented retrospectively at the time of study entry) to
death.
Secondary outcome
The secondary endpoint is the time point of HSCT. The time to this
event is the time from the first major infection or major manifestation of
immune dysregulation to HSCT.
Tertiary endpoint is the frequency of major infections or major
manifestations of immune dysregulation during the observation period.
These endpoints will be used as prognostic factors in combination with a
set of potentially predictive biomarkers in survival models in order to
establish a risk model for P-CID patients.
In addition, within this study, all patients undergoing HSCT will be
analyzed with a second set of endpoints to evaluate of the outcome of
SCT.
Primary endpoint is overall survival after 6 months and 1 year of follow up
Secondary endpoints are engraftment, immune reconstitution and
clinical outcome assessed at 6 and 12 months after HSCT.
Background summary
Combined immunodeficiencies (CID) are a heterogeneous group of
inherited immune disorders with impaired T cell development and/or
function manifesting through increased susceptibility to infections and/or
immune dysregulation. They can be delineated from SCID by their
manifestation beyond the first year of life. Profound CID (P-CID) is a
potentially life-threatening form of CID, in which SCT is a relevant
consideration at diagnosis.
The main hypothesis of this study is: P-CID patients undergoing early HSCT have
a better 5-year survival than
patients who undergo late HSCT or are not transplanted.
Study objective
The primary objective of the study is to provide natural history data on
patients with P-CID, irrespective of whether they undergo HSCT or not.
The goals are to determine survival, the frequency of severe events
and quality of life 5 years after study inclusion.
The secondary objective is to develop a risk model for P-CID patients.
The model is developed from a set of clinical and laboratory parameters
obtained at diagnosis, at study inclusion and yearly thereafter.
The tertiary objectives of this study are to determine the effects of
donor, recipient and treatment factors on the outcome of HSCT. The
goal is to determine the quality of engraftment and immunological
reconstitution and to determine the effects of these parameters on clinical
outcome.
Study design
Prospective international multicenter cohort study (observational study).
Enrolled patients will be evaluated and treated according to local
institutional protocols. They will receive comparable baseline and followup
evaluations across all participating centres, irrespective of the
therapeutic strategy at the individual site.
There will be 6 study visits (scheduled yearly) for all patients. Because of
the variable history prior to study inclusion, a morbidity score is
determined for each patient at study visit 1. For those patients
undergoing HSCT, an additional 6 months post-HSCT visit will be
documented. The study visits will document immunological parameters,
severe events including major infections and major manifestations of
immune dysregulation, severe transplant-related events and quality of
life.
Study burden and risks
There will be no risk associated with participation in this study.
There will probably be no direct benefit for the individual participants.
Albinusdreef 2
Leiden 2300RC
NL
Albinusdreef 2
Leiden 2300RC
NL
Listed location countries
Age
Inclusion criteria
Clinical and immunological criteria determine inclusion irrespective of the
genetic diagnosis.
T cell criteria (2 out of 4)
o Reduced T cell counts (CD4 : <700, if <2y ; <500, if 2-4y ; <300,
if >4y ; CD8 : <350, if <2y ; <250, if 2-4y ; <150, if >4y)
o Reduced thymic function (CD45RA+CD62L+ or CD45RA+CD31+
of CD4+ <30% <2y, <25% 2-6y, <20% >6y)
o Impaired T cell proliferation (PHA response <30% of lower limit of
normal)
o Elevated fraction of */* T cells (>15% of total CD3+ T cells)
AND Clinical criteria
* At least one major infection criteria (viral, bacterial, opportunistic)
OR
* At least one major immune dysregulation criteria (granulomas,
lymphoproliferative disease, unexplained interstitial lung disease,
inflammatory bowel disease, autoantibody mediated disease,
vasculitis) OR
* At least one malignancy criteria (lymphoid malignancies and
virally induced malignancies)
AND Age ><= 1yr and <<= 16yr at study inclusion
Exclusion criteria
No written consent available No written informed consent of
patient or parents in case of minors available or no assent of
minor if applicable;* Patients with a clinical diagnosis of SCID or Omenn syndrome
within the first year of life
* P-CID Patients for whom decision for HSCT is taken at age <1yr
* Patients with Wiskott-Aldrich syndrome and CD40 Ligand
Deficiency, because disease-specific prognosis and treatment
data are available
* Patients undergoing gene therapy or ADA enzyme replacement
will be followed using the same parameters, but will not be
included in the analysis
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | DRKS00000497 |
| CCMO | NL56821.058.16 |