Treatment of severe steroid-refractory acute GvHD with mesenchymal stromal cells.

Phase 1

• Conditions: Graft Versus Host Disease; MedDRA version: 19.1Level: PTClassification code 10066260Term: Acute graft versus host diseaseSystem Organ Class: 10021428 - Immune system disorders; MedDRA version: 19.1Level: LLTClassification code 10068908Term: AGVHDSystem Organ Class: 10021428 - Immune system disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2012-004915-30-DE
• Lead Sponsor: HOVON Foundation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-07-02
• Last Update Posted: 24 April 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 150

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
See appendices A and B for staging and response criteria;
- 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

- 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 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 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.
* Discussions with the principal investigator regarding the eligibility of a patient should always be recorded in the source documentation.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified