Graft Versus Host Disease MedDRA version: 20.0 Level: PT Classification code 10066260 Term: Acute graft versus host disease System Organ Class: 10021428 - Immune system disorders MedDRA version: 19.1 Level: LLT Classification code 10068908 Term: AGVHD System Organ Class: 10021428 - Immune system disorders
Conditions
Interventions
Product Name: mesenchymal stromal cells
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Bone marrow derived ex vivo expanded cryopreserved MSCs
CAS Number: n.a.
Current Sponsor code: n
Sponsors
HOVON Foundation
Eligibility
Sex/Gender
All
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); N.B. if histological confirmation at randomization is lacking or inconclusive but the patient is otherwise eligible and acute GvHd is considered the most likely cause of the symptoms, the patient may be included but histology of involved tissue (if lacking) should still be obtained as soon as deemed feasible and/or safe • 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). Are the trial subjects under 18? yes Number of subjects for this age range: 15 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 125 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: • Use of intravenous prophylactic MMF = 6 days prior to development of acute GvHD ; • Systemic treatment for acute GvHD other than steroids and a calcineurin inhibitor (budesonide is considered a local treatment); • Consecutive treatment with steroids = 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; N.B. if there is doubt regarding potential interference, the principal investigator should always be contacted prior to registration*. • 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 highly 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 |
|---|---|
| Main Objective: To improve the response rate to treatment of acute GvHD grade II-IV (with gut and/or liver involvement) by early addition of MSC to standardized second line treatment. ;Secondary Objective: • To study the safety of MSC addition to standardized second line treatment • To assess the incidence of treatment-related mortality • To assess the overall survival • To assess the progression-free survival • To reduce the time required for continued pharmacological immune suppression • To assess the incidence of severe bacterial, viral and fungal infections • To assess the incidence and severity of chronic GvHD • To evaluate the quality of life of patients treated with MSC in comparison with controls up to two years after MSC treatment • To establish the economic impact of MSC for the treatment of severe steroid-refractory acute GvHD (with gut and/or liver involvement) • To develop a score by means of clinical and laboratory parameters that allows for identification of patients with severe acute GvHD that will respond on MSC treatment ;Primary end point(s): Proportion of patients with complete or partial response to treatment of acute GvHD grade II-IV with (with gut and/or liver involvement) at day 29. ;Timepoint(s) of evaluation of this end point: Two interim analyses will take place after inclusion of 33% and 67% of patients. These results will be reviewed confidentially by the DSMB. Final analysis will take place when the relevant data of all patients are available. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Cumulative incidence of treatment-related mortality, defined as death not due to relapse of hematological malignancy (non-relapse mortality), at 6 months and beyond • Overall survival, defined as time from randomization until death from any cause. Patients alive at the date of last contact will be censored • Progression-free survival, defined as time from randomization until progression or relapse of hematological malignancy or death, whichever comes first • Duration of acute GvHD response, defined as time from response of acute GvHD until relapse of acute GvHD or death, whichever comes first • Time from end of systemic immunosuppressive treatment for GvHD until re-initiation of systemic immunosuppression for GvHD • Adverse events • Incidence of chronic GvHD • Quality of life • Immunological monitoring including monitoring of absolute numbers of all T-cell subsets, B-cells, and NK-cells as well as biomarkers of acute GvHD ;Timepoint(s) of evaluation of this end point: Two interim analyses will take place after inclusion of 33% and 67% of patients. These results will be reviewed confidentially by the DSMB. Final analysis will take place when the relevant data of all patients are available. | — |
Countries
Belgium, Germany, Italy, Netherlands, Spain, Sweden, United Kingdom
Contacts
Public ContactW.E. Fibbe
Principal Investigator
Outcome results
None listed