To address whether the individualized fludarabine conditioning reduces the incidence of severe viral infections at day 100 within the context of an αβTCR / CD19 depleted transplantation regimen.
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Cumulative incidence of severe viral infections at day 100.
Secondary outcome
- Non relapse mortality (NRM) at day 100
- aGVHD grade II-IV at day 100
- Donor engraftment (chimerism > 95%) at day 100
- Overall survival at day 100
- Cumulative incidence of relapse at day 100
- Effective fludarabine exposure
- Cost effectiveness at 2 years
Background summary
Allogeneic stem cell transplantation (allo-SCT) is still the treatment of
choice for many patients suffering from hematological malignancies, which can
only occasionally be cured with conventional chemotherapy. Allo-SCT still
associates with a high transplant related morbidity and mortality. Fludarabine
(FLU) is part of many regimens utilized for conditioning. Recent analysis of a
retrospective allo-SCT patient cohort has shown that high exposure of FLU
results in an increased risk of viral infections and subsequent change of
non-relapse mortality.
With *individualized dosing of FLU* (section C4) we aim to reduce the change of
overexposure to FLU, which to diminish the change of infectious complications.
Study objective
To address whether the individualized fludarabine conditioning reduces the
incidence of severe viral infections at day 100 within the context of an
αβTCR / CD19 depleted transplantation regimen.
Study design
Prospective, multicenter, open label randomized, phase II study
Intervention
Patients will be randomized to either to standard dosing of fludarabine or
individualized fludarabine dosing as part of a conditioning regimen, followed
by an αβTCR / CD19 depleted transplantation.
Study burden and risks
The protocol comprises a different dosing of fludarabine in the experimental
arm. All other acts, measurements, follow-up and level of care are therefore
similar to off-study patients undergoing allo-SCT. The burden of the therapy is
associated with the allo-SCT itself, which is a necessary therapeutic
intervention in all subjects. Possible increased risks for the recipient are
graft failures, although not observed so far in all cohorts with the intended
dose levels. The intended target level of fludarabine remains in the range of
all so far treated patients at the UMCU. We only propose to avoid too high
exposure to fludarabine
Heidelberglaan 100
Utrecht 3508 GA
NL
Heidelberglaan 100
Utrecht 3508 GA
NL
Listed location countries
Age
Inclusion criteria
1. Adults (>= 18 years)
2. AML, MDS, ALL, CML, CLL, NHL, HL, or a myeloproliferative disease (MPD)
3. Indication for allo-SCT according to the policy of the local center
4. WHO performance status <= 2
5. Written informed consent
Exclusion criteria
1. Relapse of disease within 5 months after previous allo-SCT
2. Bilirubin and/or transaminases > 2.5 x normal value*
3. Creatinine clearance < 40 ml/min
4. Cardiac dysfunction as defined by:
- Unstable angina or unstable cardiac arrhythmias
- NYHA classification > II (Appendix B)
- Cardiac symptoms and/or history of cardiac disease AND a cardiac ejection
fraction <45%
5. Active, uncontrolled infection
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
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-000356-18-NL |
| CCMO | NL64877.041.18 |
| OMON | NL-OMON24753 |