CD40-L Blockade for Prevention of Acute Graft-Versus-Host Disease

BMS-986004 will be administered in ascending dose cohorts in the phase I component of the trial. Based on prior PK and PD data, dose levels of 225 mg, 675 mg, and 1500 mg (3 total phase I dose levels) will be examined. BMS-986004 will be given intravenously (IV) every 2 weeks, starting from day -3 (i.e., three days prior to HCT) onward through a total of 100 days post-HCT. The maximum tolerated dose (MTD) identified in the phase I component of the trial will be carried forward as the recommended dose level in the phase 1 expansion cohort.

"Sirolimus and tacrolimus (standard of care pharmacologic immune suppression) will be given according to institutional standards.~Sirolimus (SIR) will be given as a loading dose on day -1 orally, then daily as maintenance therapy with target levels of 10-14ng/mL early post-HCT, then tapered to 5-14ng/mL range.~Program standards will be used for SIR and TAC level monitoring frequency and dose adjustments, including careful attention to drug-interactions."

"Sirolimus and tacrolimus (standard of care pharmacologic immune suppression) will be given according to institutional standards.~In brief, tacrolimus (TAC) will be started on day -3 IV, and transitioned to oral TAC when oral medications are tolerated; target level is 3-7ng/mL.~Program standards will be used for SIR and TAC level monitoring frequency and dose adjustments, including careful attention to drug-interactions."