Infusion of mesenchymal stem cells as treatment for steroid resistant grade II to IV acute GVHD or poor graft function: a multicenter phase II study

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 10

Inclusion Criteria

Patient eligibility criteria
-male or female of any age
-previous allogenic transplantation (related or unrelated donor, any degree of HLA matching) or autologous transplantation (for oart two only) or HSC at any time before.
- any source of HSC (marrow, PBSC, cord blood) and any conditioning regimen
- informed consent given by donor or his/her guardian if of minor age;MSC donor inclusion criteria
1. related to the recipent (sibling, parent or child) or unrelated
2. male or female
3. age> 16 yrs (no age limit if same as HSC donor)
4. no HLA matching required
5. fulfills generally accepted criteria for allogeneic HSC donation
6. informed consent given by donor or his/her guardian if of minor age;Additional criteria for each part of the protocol:
part 1: MSC for steroid-refractory grade II-IV acute GvHD
1. allogeneic transplantation
- grade II-IV acute GvHD refractory to mPDN 2 mg/kg/day or equivalent
2. ongoing therapy with ciclosporine or tacrolimus at therapeutic doses
3. patient may have received previously any other form of treatment for acute GvHD, but no new treatment started within 1 month of study entry;part 2: MSC for poor graft function (PGF)
1. allogeneic or autologous transplantation
- cytopenia in 2 or 3 lineages OR severe cytopenia in 1 lineage
2. cytopenia duration 2 weeks beyond day 28 after autologous HCT, or day 42 (day 60 for cord blood transplantation) after allogeneic HCT
3. cytopenia is not related to CMV or other infection, myelosuppressive/toxic drugs, renal failure, peripheral cell destruction or other identifiable cause
4. in case of HLA-identical related donor and full donor chimerism, patient can only be included if a boost of donor CD34+ cells has been unsuccessful or is not feasible;part 3: MSC + DLI for poor donor T-cell chimerism
1. allogeneic transplantation
2. donor T-cell chimerism < 50% for at least 2 consecutive weeks beyond day 21 after HCT OR 20% decrease in donor T-cell chimerism with the second value < 50%

Exclusion Criteria

Patient
- HIV postive
- active uncontrolled infection at time of scheduled MSC infusion
- relapsing or progressing malignancy;MSC donor exclusion criteria
1. HIV positive
2. known allergy to lidocaine
3. if donor other than HSC donor: any risk factor for transmissible infectious diseases

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary endpoint:<br /><br>To establish efficacy of infusions of MSC from related HLA-identical,<br /><br>HLA-haploidentical or mismatched unrelated donors:<br /><br>1. Part 1: MSC for steroid-refractory grade II-IV acute GVHD : efficacy on<br /><br>steroid-resistant grade II - IV acute GVHD.<br /><br>2. Part 2: MSC for poor graft function (PGF) : efficacy on PGF.<br /><br>3. Part 3: MSC + DLI for poor donor T-cell chimerism after allogeneic HCT :<br /><br>efficacy on prevention of graft rejection in patients with low or<br /><br>failing donor T-cell chimerism after allogeneic HCT.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints:<br /><br>1. Toxicity of MSC infusions<br /><br>2. Incidence of acute (Appendix A) and chronic GVHD (Appendix B).<br /><br>3. Overall and progression-free survival.<br /><br>4. Incidence of bacterial, fungal and viral infections.<br /><br>5. Disease progression or relapse.<br /><br>6. Evidence of epithelial cells of MSC donor origin (assessed by STR-PCR) in<br /><br>bone marrow (and organs affected by GVHD : for part 1 only) after MSC infusion.</p><br>

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