graft-versus-host disease, steroid-refractory
Conditions
Interventions
Eligible patients will be randomized to either standardized second line treatment only, consisting of mycophenolate mofetil (MMF) in combination with a placebo for MSC infusion, or MMF in combination
Sponsors
HOVON Data Center
Eligibility
Inclusion criteria
Inclusion criteria: •Grade II-IV acute GvHD with gut and/or liver involvement, confirmed by histology of involved tissues (in case of gut and liver involvement histology of either one of these tissues is considered sufficient); • Non-responsive to treatment with steroids and a calcineurin-inhibitor defined as: - progressive disease or mixed response after 5 days of consecutive systemic treatment with steroids at a dose of 2 mg/kg and a calcineurin-inhibitor at therapeutic trough levels. - stage 4 GvHD of gut and/or liver and deterioration of clinical parameters (gut) or increase of serum total bilirubin levels in umol/L (liver) after 5 days of consecutive systemic treatment with steroids at a dose of 2 mg/kg and a calcineurin-inhibitor at therapeutic trough levels - stable disease after 10 days of consecutive systemic treatment with steroids at a dose of 2 mg/kg and a calcineurin-inhibitor at therapeutic trough levels. - progressive disease after initial partial response of maximal 1 grade after 10 days of consecutive systemic treatment with steroids at a dose of 2 mg/kg and a calcineurin- inhibitor at therapeutic trough levels. • Any age; • Lansky / Karnofsky score of ≥20; • Signed informed consent by the patient and/or parent(s) or legal guardian(s).
Exclusion criteria
Exclusion criteria: • Use of prophylactic MMF, Myfortic or other systemic treatment for acute GvHD ≤ 6 days prior to development of acute GvHD grade II-IV with gut and/or liver involvement; • Systemic treatment for acute GvHD other than steroids and a calcineurin inhibitor (budesonide is considered a local treatment); • Previous treatment with MSC; • Progressive or relapsing malignant disease in case of NHL, HL, CLL, MM, and ≥ 5% blasts in the bone marrow in case of AML, ALL, CML; • Requiring ventilator or vasopressor support; • Poor performance not expected to survive 14 days; • Known seropositivity of HIV, Hepatitis B and C, HTLV; • Known uncontrolled toxicity for DMSO; • Known anaphylactic reaction to penicillin or streptomycin; • Known pregnancy; • Any psychological, familial, sociological and /or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of patients responding to treatment of acute GvHD grade II-IV (with gut and/or liver involvement) at day 29. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Overall survival 2. Progression-free survival 3. Duration of acute GvHD response 4. Time without systemic immunosuppression 5. Cumulative incidents of non-relapse mortality 6. Adverse events 7. Incidence of chronic GvHD 8. Quality of life 9. Immune reconstitution including monitoring of absolute T-cell subsets, B-cells, NK-cells as well as biomarkers of acute GvHD | — |
Contacts
Public ContactW.E. Fibbe
Head of dept Immunohematology and Bloodtransfusion (E3-Q) Leiden University Medical Center P.O.Box 9600
Outcome results
None listed