A Prospective Study of Remestemcel-L, Ex-vivo Cultured Adult Human Mesenchymal Stromal Cells, for the Treatment of Pediatric Participants Who Have Failed to Respond to Steroid Treatment for Acute Graft-Versus-Host Disease (aGVHD)

1. Participant is diagnosed with Grade B-D acute GVHD requiring corticosteroid systemic therapy. The participant may have Grade C or D aGVHD involving the skin, liver, and/or GI tract or may have Grade B aGVHD involving the liver and/or GI tract, with or without concomitant skin disease. Acute GVHD is defined as the presence of skin rash and/or persistent nausea, vomiting, and/or diarrhea and/or cholestasis presenting in a context in which aGVHD is likely to occur and where other etiologies such as drug rash, enteric infection, or hepatotoxic syndromes are unlikely or have been ruled out.

2. Participant has failed to respond to steroid treatment, with failure to respond defined as any Grade B-D \[International Bone Marrow Transplant Registry (IBMTR) grading\] aGVHD that shows progression within 3 days, or no improvement within 7 days of consecutive treatment with 2 mg/kg/day methylprednisolone or equivalent.

3. Participant must be able to be treated with remestemcel-L within 4 days of signing of informed consent.

4. Participants who have had persistent GI GVHD manifested by diarrhea with stool volume \< 500 mL/kg/day (for participants \>50 kg) or \<30 mL/kg/day (for participants ≤50 kg). See GVHD Organ Severity Criteria (Table 2) for values in mL/m\^2. In the absence of nausea or vomiting, participants could have been considered to have Grade B GVHD if:

1. other causes of diarrhea had been ruled out (eg, Clostridium difficile, adenovirus or cytomegalovirus \[CMV\] infection, or oral magnesium administration), and if

2. the low stool volume reflected the effects of fasting, narcotics, or antidiarrheal medications.

5. Participant must have adequate renal function as defined by a calculated creatinine clearance of \>30 mL/min per 1.73 m\^2. For participants 1 to 18 years of age, creatinine clearance is calculated using the Bedside Schwartz equation:

Glomerular filtration rate (GFR, in mL/min per 1.73 m\^2) = (0.413 \* height \[cm\])/serum creatinine (mg/dL)

For participants younger than 1 year of age, renal function is determined using the Schwartz equation adjusted for this age group:

Creatinine clearance (mL/min per 1.73 m\^2= (height \[cm\] x 0.45)/ (serum creatinine \[mg/dL\]).

6. Participant has a minimum Karnofsky/Lansky Performance Level of at least 30 at the time of study entry.

7. Participant (or legal representative where appropriate) must be capable of providing written informed consent.

8. Female participants of childbearing potential (≥10 years of age) are required to use a medically accepted method of contraception and to agree to continue use of this method for the duration of the study and for the follow-up time period. Acceptable methods of contraception include abstinence, barrier method with spermicide, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method.

9. Male participants with partners of childbearing potential must agree to use adequate contraception (barrier method or abstinence) during the study, including the follow-up time period.

10. The participant must be willing and able to comply with study requirements, remain at the clinic, and return to the clinic for the follow-up evaluation during the study period, as specified in this protocol.

What this study is about