Patients aged 18 -65 years inclusive, with high-risk hematological disease, eligible for allo MUD-SCT, lacking a matched unrelated donor and with availability of 2 (¡Ý 4/6) matched UCB units
Conditions
Interventions
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 day
Sponsors
HOVON Data Center
Eligibility
Inclusion criteria
Inclusion criteria: 1. Age 18-65 years inclusive; 2. Diagnosis of poor-risk hematological malignancy or (V)SAA relapsing after or failing immunosuppressive therapy and meeting the criteria for a MUD allo SCT; 3. 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; 4. Availability of 2 (≥4/6) matched UCB grafts with a total nuclear cell count > 4 x 107/kg (see paragraph 8.2); 5. WHO performance status 0-2; 6. Written informed consent.
Exclusion criteria
Exclusion criteria: 1. Bilirubin and/or transaminases > 2.5 x normal value; 2. Creatinine clearance < 40 ml/min; 3. Cardiac dysfunction as defined by: A. Reduced left ventricular function with an ejetion fraction < 45% as measured by MUGA scan or echocardiogram (another method for measuring cardiac function is acceptable); B. Unstable angina; C. Unstable cardiac arrhythmias. 4. Pulmonary function test with VC, FEV1 and/ or DCO < 50%; 5. Active, uncontrolled infection; 6. History of high dose (≥ 8 Gy) total body irradiation; 6. Pregnant or lactating females; 7. HIV positivity.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Cumulative incidence of engraftment; 2. Cumulative incidence of graft failure; 3. Time to neutrophil recovery; 4. Time to lymphocyte recovery; 5. Time to platelet recovery; 6. Time to red blood cell transfusion independence; 7. Count of total CD3+, CD4+,CD8+ and CD19+ cells and CD3-CD16/56+ cells at 1,2, 3, 6, 12 and 24 months after UCBT; 8. Incidence and grade of acute GVHD; 9. Incidence of chronic GVHD; 10. Incidence of infections; 11. Transplant related mortality (TRM; defined as non-relapse mortality); 12. Progression free survival (PFS, i.e. time from transplantation until progression/relapse or death from any cause, whichever comes first); 13. 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. | — |
Contacts
Public ContactJ.J. Cornelissen
Erasmus Medical Center, Daniel den Hoed Cancer Center, Department of Hematology, P.O. Box 5201
Outcome results
None listed