Early Treatment of Acute Graft Versus Host Disease With Bone Marrow-Derived Mesenchymal Stem Cells and Corticosteroids

Launched by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE (NHLBI) · Mar 4, 2015

Keywords

ClinConnect Summary

This is a pilot study evaluating the addition of bone marrow-derived mesenchymal stem cell (BMSC) infusions to corticosteroids for the early treatment of acute graft versus host disease (GVHD). Acute GVHD is a major complication following allogeneic stem cell transplant. GVHD occurs when T-lymphocytes in the donor graft respond to signals from recipient cells and cause tissue damage. This process can lead to organ injury, increased risk of infection, and graft failure. Corticosteroids have been used as the primary therapy for acute GVHD for decades, and guidelines currently recommend their ...

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Eligibility criteria

• * INCLUSION CRITERIA:
• • History of any grade acute GVHD requiring systemic therapy after allogeneic stem cell transplant or DLI.
• • --Subjects must have received an allogeneic stem cell transplant at NIH and be diagnosed with acute GVHD. Acute GVHD is defined using the NIH consensus definition inclusive of classic acute (less than or equal to 100 days after transplant or DLI, presence of acute GVHD features, absence of chronic GVHD features) AND persistent/recurrent/late onset acute (\> 100 days after transplant or DLI, presence of acute GVHD features, absence of chronic GVHD features). Subjects with stage I and II skin only (overall Grade I) or isolated upper gastrointestinal involvement are eligible if the treating physician deems that systemic corticosteroid treatment is indicated. Biopsy confirmation of GVHD is desirable, but not required for study entry because enrollment should not be delayed awaiting biopsy or pathology results. Patients must be diagnosed with a first episode of acute GVHD requiring systemic corticosteroids and associated with preceding administration of a cellular therapy including stem cells and donor lymphocyte infusion. Patients who were treated for GVHD associated with another cellular therapy product (e.g. prior allogeneic transplant or DLI) will be allowed into the study.
• • Previous immunosuppressive therapy
• • The patient must have received no systemic immune suppressive therapy for treatment of new acute GVHD (e.g. pentostatin, etanercept, denileukin difitox, etc.), except for a maximum 120 hours prior corticosteroid therapy. This does not include immune suppressive therapy for GVHD prophylaxis (e.g. calcineurin inhibitor, sirolimus, MMF, etc.). It is expected that most patients will be receiving GVHD prophylaxis as part of their transplant regimen, thus patients developing acute GVHD while on GVHD prophylaxis will still be considered eligible. Concurrent or addition of locally-acting steroid therapy (skin creams, oral budesonide, or any other locally-acting steroid preparation) is allowed.
• • There is one exception to the above stipulations: Use of the oral medication MMF (in addition to systemic corticosteroids) for the treatment of acute GVHD will be allowed. MMF is commonly given early in the treatment of acute GVHD, but it has not been shown to improve outcomes compared to steroids alone in a randomized, prospective study; therefore, treatment with MMF will not exclude patients from BMSC treatment.
• • Age: Age greater than or equal to 4 years old will be allowed.
• • Birth control: Subjects of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated on this study.
• • Informed consent: Signed informed consent and/or assent is required. Assent and educational materials will be provided to, and reviewed with, patients under the age of 18. The informed consent process will begin at recognition of patient eligibility.
• EXCLUSION CRITERIA:
• • Breast feeding or pregnant females (due to unknown risk to fetus or newborn).
• • Known allergy to gentamicin.