Mesenchymal Stem Cell Infusion as Treatment for Steroid-Resistant Acute Graft Versus Host Disease (GVHD) or Poor Graft Function

Launched by UNIVERSITY OF LIEGE · Jan 28, 2008

Keywords

ClinConnect Summary

This clinical trial is studying the use of mesenchymal stem cell (MSC) infusions as a potential treatment for patients experiencing severe complications after receiving stem cell transplants. These complications include acute graft-versus-host disease (GVHD), which happens when the donor's immune cells attack the recipient's body, and poor graft function, where the transplanted stem cells do not work properly. The trial has three parts: one focuses on patients with steroid-resistant acute GVHD, the second looks at those with poor graft function, and the third examines patients with low donor T-cell chimerism, which means the donor's immune cells are not adequately present in the recipient’s body.

Anyone who has had a stem cell transplant may be eligible to participate, regardless of their age or gender. To qualify, patients must have specific issues related to their transplant, such as ongoing severe GVHD despite steroid treatment or low blood cell counts that last longer than expected after their transplant. Participants can expect to receive MSC infusions and will be monitored to see how well this treatment helps their condition. It’s important to note that this study is currently recruiting patients, and participants must give informed consent before joining. If you or someone you know is facing these serious post-transplant complications, this trial could offer a new treatment option.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Patient eligibility criteria
• • 1. Male or female of any age.
• • 2. Previous allogeneic transplantation (related or unrelated donor, any degree of HLA matching) or autologous transplantation (for part 2 only) of HSC at any time before.
• • 3. Any source of HSC (marrow, PBSC, cord blood) and any conditioning regimen.
• • 4. Informed consent given by donor or his/her guardian if of minor age.
• 5. Additional criteria for each part of the protocol:
• • Part 1: MSC for steroid-refractory grade II-IV acute GVHD
• • 1. Allogeneic transplantation.
• • 2. Grade II-IV acute GVHD (see appendix A for acute GVHD grading) de novo or following DLI.
• • 3. Acute GVHD refractory to mPDN 2 mg/kg/day or equivalent, defined as
• • progression of GVHD on day 3 after initiation of steroids
• • no improvement of GVHD on day 7 after initiation of steroids
• • absence of complete resolution of acute GVHD on day 14 after initiation of steroids
• • relapse of acute GVHD during or after steroid taper.
• • 4. Ongoing therapy with Ciclosporine or Tacrolimus at therapeutic doses.
• • 5. 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.
• 2. Cytopenia in 2 or 3 lineages:
• • Hb \< 8.0 g/dL and reticulocytes \< 1%, with or without transfusion
• • Plt \< 20,000/µL without transfusion
• • Neutrophils \< 500/µL, without G-CSF administration
• OR severe cytopenia in 1 lineage:
• • RBC transfusion dependent (if autologous transplantation; despite EPO administration if allogeneic transplantation)
• • Plt transfusion dependent
• • Neutrophils \< 500/µL despite G-CSF administration
• • 3. Cytopenia duration ≥ 2 weeks beyond day 28 after autologous HCT, or day 42 (day 60 for cord blood transplantation) after allogeneic HCT.
• • 4. Cytopenia is not related to CMV or other infection, myelosuppressive/toxic drugs, renal failure, peripheral cell destruction or other identifiable cause.
• • 5. 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. Nonmyeloablative 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%.
• • MSC donor inclusion criteria
• • 1. Related to the recipient (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.
• Exclusion Criteria:
• • Patient exclusion criteria
• • 1. HIV positive.
• • 2. Active uncontrolled infection at time of scheduled MSC infusion.
• • 3. 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.