This is a Phase III, randomized, double-blind, placebo-controlled study to investigate the efficacy and safety of Prochymal® versus placebo in combination with corticosteroids as initial therapy for acute GVHD. Corticosteroids have been the primary therapy for patients with previously untreated acute GVHD and the historical published data define an expected 35% complete response (CR) at Day +28 using this therapy.
Participants will be treated with a total of 6 infusions of investigational agent during the first 4 weeks of the study. The first infusion of the investigational product (IP) will be administered within 72 hours of the start of systemic corticosteroid therapy. Four infusions will be administered during the first two weeks (twice weekly), then two infusions administered during the next two weeks (once weekly). Participants assigned to the active treatment group will receive Prochymal®. Participants assigned to the non active treatment group will receive placebo (excipient, less cells). It is recommended that all participants receive all six infusions. The discontinuation of investigational agent is allowed for GVHD worsening with subsequent need for salvage therapy. All infusions must be given at least 3 days apart. Participants will be evaluated for efficacy and safety until death, withdrawal or 90 study days after randomization, whichever occurs first. Study will be unblinded and data analyzed at Day 90 post 1st infusion (Day 0) following final participant enrollment. Participants will be followed for safety for 12 months post 1st infusion (Day 0).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
192
Prochymal® intravenous infusion.
Placebo-matching Prochymal® intravenous infusion.
Administration will be intravenously as prescribed by the caregiver.
Percentage of Participants with Treatment Success
Treatment was considered a success if all of the following conditions were met: Achieved induction of a complete response (CR) within 28 days after first infusion; CR followed by 28 days maintenance of a clinically meaningful response defined as the response that did not require an increase in corticosteroid dose (methylprednisolone doses \>2 milligram/kilogram/day \[mg/kg/d\] or prednisone doses \>2.5 mg/kg/d) for more than 7 consecutive days; Did not require second line/escalation therapy through Study Day 56; and survived 90 study days.
Time frame: 90 Days
Percentage of Participants with Overall Response
Overall Response was defined as participants who achieved complete response or partial response (CR+PR).
Time frame: Day 90
Percentage of Participants with Induction of a 2-grade decrease in (Graft Versus Host Disease) GVHD by Study Day 28 with maintenance of a 2-grade decrease in GVHD through Study Day 56
Time frame: Up to Day 56
Percentage of Participants with Induction of CR lasting for greater than or equal to 14 Days
Time frame: Day 14
Percentage of Participants with Induction of a CR after Study Day 28 and clinically managed with steroids with second line/escalation therapy through Study Day 56
Time frame: Up to Day 56
Percentage of Participants with Induction of PR during the first 28 days
Time frame: Up to Day 28
Time to achieve CR
Time frame: Up to Day 90
Number of CR per organ
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Time frame: Up to Day 90
Total corticosteroid dose administered
Time frame: Up to Day 90
Number of corticosteroid-related complications
Corticosteroid-related complications included hyperglycemia requiring insulin, corticosteroid myopathy and psychosis.
Time frame: Up to Day 90
Number of Infectious complications
Infectious complications included viral, fungal or bacterial complications.
Time frame: Up to Day 90
Number of Days of Hospitalization
Time frame: Up to Day 90
Average Daily Corticosteroid Dose
Time frame: Up to Day 90