HOVON 113

Originele protocol

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 the patient is otherwise eligible but histological confirmation at randomization is lacking, the principal investigator should be contacted.*
• Non-responsive to consecutive systemic treatment with steroids at a dose of 2 mg/kg and a calcineurin-inhibitor at therapeutic trough levels, defined as:
  • progressive disease or mixed response after 5-6 days of treatment.
  • stage 4 GvHD of gut and/or liver after 5-6 days treatment and:
    significant deterioration of clinical parameters (gut) OR
    increase of serum total bilirubin levels in umol/L (liver)
    not attributable to other causes than acute GvHD
  • progressive disease after initial partial response of maximal 1 grade after 5-7 days of treatment
  • stable disease after 7 days of treatment
    See appendix A for response criteria
• Any age;
• Lansky / Karnofsky score of ≥20;
• Signed informed consent by the patient and/or parent(s) or legal guardian(s).

Exclusion criteria

• Use of prophylactic MMF or Myfortic ≤ 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);
• Pre-treatment with steroids ≥ 1 mg/kg for more than 3 days prior to initiation of steroids at a dose of 2 mg/kg for the treatment of acute GvHD;
• Previous treatment with advanced therapy medicinal products (ATMP) potentially interfering with the endpoints of this study; N.B. if the patient has previously been treated with ATMP, the principal investigator should always be contacted prior to registration*.
• 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.
  * Discussions with the principal investigator regarding the eligibility of a patient should always be recorded in the source documentation