No registrations found.
ID
Source
Brief title
Health condition
single cord blood transplantation
stemregenin-1 expanded hematopoietic stem cells
engraftment
Sponsors and support
Intervention
Outcome measures
Primary outcome
Feasibility as defined by, and to be achieved in ≥ 80% of (evaluable) patients:
1. SR-1 mediated expansion, resulting in > 20-fold expansion of CD34+ cells, and
2. effective hematopoietic (neutrophils > 0.5 x 109/L) engraftment within 30 days upon transplantation
Secondary outcome
Cumulative incidence of engraftment
Cumulative incidence of graft failure
Time to neutrophil recovery (> 0.5 x 109/L)
Time to lymphocyte (T-cells + subsets; B-cells; NK-cells) recovery
Time to platelet recovery ( > 20 x 109/L)
Time to red blood cell transfusion independence
Absolute number of CD3+CD4+, CD3+CD8+, CD19+ and CD3-CD16/56+ cells at 1,2, 3, 6, 12 and 24 months after UCBT
Incidence and grade of acute GVHD
Incidence of chronic GVHD
Incidence of infections
Incidence of CTC grade 3-4 adverse events
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. Patients still alive or lost to follow up
are censored at the date they were last known to be alive
Background summary
Rationale:
Insufficient hematopoietic recovery following UCBT is considered to be primarily due to the low number of hematopoietic stem cells in UCB grafts. In-vitro stem cell expansion can be achieved by SCF, Flt3L, TPO and Stemregenin-1 (SR-1). Transplantation of double UCBT including one SR-1 expanded unit was recently demonstrated feasible and safe. The present study aims to evaluate feasibility, engraftment and recovery following transplantation of one expanded unit.
Study objectives:
To study the feasibility of single UCBT with one ex-vivo SR-1 expanded unit
To assess side effects and TRM after single UCBT with one expanded unit
To assess engraftment and engraftment kinetics; to evaluate immune reconstitution, acute and chronic GVHD, chimerism, toxicity, progression-free survival and overall survival after single UCBT with one expanded unit.
Intervention:
Patients are treated with a reduced-intensity conditioning regimen, irrespective of patient age, followed by single UCBT, using one SR-1 expanded unit. Post grafting immunosuppression is performed by mycophenolate mofetil (30 days) and cyclosporine A (90 days, taper thereafter)
Duration of treatment:
Patients will be treated with a conditioning regimen during 7 days, followed by transplantation. Subsequent immunosuppression may take up to 180 days.
Patients will be followed until 5 years after registration
Expected duration of accrual: 1 year
Main study endpoint:
Feasibility as defined by, and to be achieved in ≥ 80% of (evaluable) patients:
1. SR-1 mediated expansion, resulting in > 20-fold expansion of CD34+ cells, and
2. effective hematopoietic (neutrophils > 0.5 x 109/L) engraftment within 30 days upon transplantation
Benefit and nature and extent of the burden and risks associated with participation
Benefits for individual patients may include a faster and better hematopoietic recovery, less opportunistic infections after transplantation and less graft versus host disease as compared to double UCBT
Risks of participation include graft failure and autologous recovery
Planned interim analysis and DSMB
An interim analysis will take place after the first 5 patients have been included and are found to be eligible and will be discussed with the DSMB.
Study design
At entry: within 30 days before start of treatment
After 1, 2, 3, 6, 12 and 24 months after transplantation and yearly therafter
Intervention
Patients are treated with a reduced-intensity conditioning regimen, irrespective of patient age, followed by single UCBT, using one SR-1 expanded unit. Post grafting immunosuppression is performed by mycophenolate mofetil (30 days) and cyclosporine A (90 days, taper thereafter)1.
P.O. Box 5201
J.J. Cornelissen
Rotterdam 3008 AE
The Netherlands
+31 (0)10 4391598 or +31 (0)10 4391367
j.cornelissen@erasmusmc.nl
P.O. Box 5201
J.J. Cornelissen
Rotterdam 3008 AE
The Netherlands
+31 (0)10 4391598 or +31 (0)10 4391367
j.cornelissen@erasmusmc.nl
Inclusion criteria
- Age 18-70 years inclusive
- Diagnosis of poor-risk hematological malignancy 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 1 (≥5/6) matched UCB graft with a nuclear cell count > 2,7 x 107/kg (see paragraph 8.2).
- Availability of an back-up autograft, harvested and frozen earlier in the course of treatment, (harvest according to local aphersis policies)
- 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 by:
Reduced left ventricular function with an ejection fraction < 45% as measured by MUGA scan or echocardiogram (another method for measuring cardiac function is acceptable)
Unstable angina
Unstable cardiac arrhythmias
- Pulmonary function test with VC, FEV1 and/ or DCO < 50%
- Active, uncontrolled infection
- History of high dose (≥ 8 Gy) total body irradiation
- Pregnant or lactating females
- HIV positivity
Design
Recruitment
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 |
|---|---|
| NTR-new | NL6082 |
| NTR-old | NTR6229 |
| Other | METC Erasmus MC : MEC 2016-689 |