Graft versus Host Disease
Conditions
Interventions
Patients are randomized for
- treatment with mycophenolate mofetil (MMF) and MSC, or
- treatment with MMF and placebo
Sponsors
HOVON
Eligibility
Age
2 Years to 99 Years
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); • Steroid-refractory defined as progressive disease, mixed response, or grade IV disease after at least 5 days, or stable grade II-III disease after at least 7 days of consecutive systemic treatment with steroids at a dose of >= 2 mg/kg prednisolone or steroid equivalent 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 intravenous prophylactic MMF = 2 mg/kg prednisolone or steroid equivalent > 10 days directly prior to inclusion; • Previous treatment with advanced therapy medicinal products (ATMP) potentially interfering with the endpoints of this study; • Known 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 uncontrolled hypersensitivity to DMSO; • History of any other malignancy, unless diagnosed and treated > 5 years ago with curative intent and without recurrence or nonmelanoma skin cancer and/or carcinoma in situ of any type following complete resection. • Known pregnancy, a positive higly sensitive pregnancy test at screening, or lactation for female patients; unwillingness to practice highly effective means of contraception for both female and male patients of reproductive potential, as described in paragraph 9.4. • 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. Cumulative incidence of treatment-related mortality, defined as death not due to relapse of hematological malignancy (non-relapse mortality), at six months and beyond 2. Overall survival, defined as time from randomization until death from any cause. Patients alive at the date of last contact will be censored 3. Progression-free survival, defined as time from randomization until progression or relapse of hematological malignancy or death, whichever comes first 4.Duration of acute GvHD response, defined as time from response of acute GvHD until relapse of acute GvHD or death, whichever comes first 5. Time from end of systemic immunosuppressive treatment for GvHD until re-initiation of systemic immunosuppression for GvHD 6. Adverse events 7. Incidence of chronic GvHD 8. Quality of life 9. Immunological monitoring including monitoring of absolute numbers of all T-cell subsets, B-cells, and NK-cells as well as biomarkers of acute GvHD | — |
Countries
Netherlands
Outcome results
None listed