Objective of the study is to evaluate whether parameters can be identified that predict which graft ultimately prevails following cord blood transplantation after a reduced intensity conditioning regimen in adult patients .In addition engraftment,…
ID
Source
Brief title
Condition
- Haematological disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- The proportion of patients with activated class II-specific T-cells (aTCs),
defined as: the number of patients with aTCs, divided by the number of patients
with class II mismatches for which there are tests available (defined as
evaluable patients).
- Transplant related mortality (TRM; defined as non-relapse mortality)
Secondary outcome
- Cumulative incidence of engraftment
- Cumulative incidence of graft failure
- Time to neutrophil recovery
- Time to lymphocyte recovery
- Time to platelet recovery
- Time to red blood cell transfusion independence
- Count of total CD3+, CD4+ and CD8+ cells and CD3-CD16/56+ cells at 3, 6, 12
and 24 months after UCBT
- Incidence and grade of acute GVHD
- Incidence of chronic GVHD
- Incidence of infections
- Progression free survival (PFS, i.e. time from transplantation until
progression/relapse or death from any cause, whichever comes first)
- Overall survival (OS) calculated from transplantation.
Background summary
Many adults with high risk hematological disease can not proceed to allogeneic
stem cell transplantation because they
lack a matched unrelated stem cell donor. Cord blood transplantation has shown
to be an important alternative stem
cell source in children. The major problem after a single cord blood
transplantation in adults appears to be primary graft
failure and a delayed hematopoietic recovery caused by the small number of
hematopoietic stem cells in cord blood
grafts. Double cord blood transplantation has shown to be a safe and promising
approach in adult to overcome this
problem and has become standard treatment in adult patients who qualify for
alternative donor transplantation and lack a properly matched unrelated donor.
Sustained hematopoiesis is usually derived from a single donor after double
umbilical cord blood
transplantation.So far, the distinct contributing factors which lead to the
predominance of the prevailing cord blood graft
are not known.
Study objective
Objective of the study is to evaluate whether parameters can be identified that
predict which graft ultimately prevails following cord blood transplantation
after a reduced intensity conditioning regimen in adult patients .
In addition engraftment, transplant related mortality and disease-free survival
will be evaluated .
Study design
Prospective phase II study. Patients eligible for allogeneic stem cell
transplantation lacking a matched unrelated donor
are transplanted with a double cord blood graft. Transplantation will be
preceded by a reduced-intensity conditioning
regimen. After transplantation blood samples and bone marrow samples will be
collected at certain time points.
Intervention
Patients are treated with a reduced-intensity conditioning regimen,
irrespective of patient age, followed by double UCBT. Post grafting
immunosuppression is performed by mycophenolate mofetil (30 days) and
cyclosporine A (90 days, taper thereafter)
Study burden and risks
Nature and extend of the burden and risks associated with participation.
Burden and risk are comparable to burden and risk of a standard cord blood
transplant procedure. Collection of blood
samples may be a small extra burden if extra venous puncture is necessary.
Collection of bone marrow samples can
give a small inconvenience because a larger volume of bone marrow has to be
collected compared to standard bone
marrow examination.
VUMC, HOVON Centraal Bureau, De Boelelaan 1117
Amsterdam 1081 HV
NL
VUMC, HOVON Centraal Bureau, De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
- Age 18-70years inclusive
- Diagnosis of poor-risk hematological malignancy or (V)SAA relapsing after or failing immunosuppressive therapy and meeting the criteria for a MUD allo SCT
- Lacking a sufficiently matched volunteer unrelated donor or lacking such a donor within the required time period of <= 2 months in case of urgently needed alloSCT
- Availability of 2 (>=4/6) matched UCB grafts with a total nuclear cell count > 4 x 107/kg (see paragraph 8.2).
- WHO performance status 0-2
- Written informed consent
Exclusion criteria
- Bilirubin and/or transaminases > 2.5 x normal value
- Creatinine clearance < 40 ml/min
- Cardiac dysfunction (as defined in protocol in 8.1.2)
- Pulmonary function test with VC, FEV1 and/ or DCO < 50%
- Active, uncontrolled infection
- History of high dose total body irradiation
- Pregnant or lactating female
- HIV positivity;
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2012-001188-55-NL |
| CCMO | NL40329.000.12 |