Ignite Creation Date:
2024-05-06 @ 8:03 PM
Last Modification Date:
2024-10-26 @ 3:19 PM
Study NCT ID:
NCT06233110
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-11
First Post:
2024-01-22
Brief Title:
Ruxolitinib Plus Fostamatinib for Steroid Refractory CGvHD
Sponsor:
Stefanie Sarantopoulos MD PhD
Organization:
Duke University
Study Overview
Official Title:
Phase I Trial of Ruxolitinib Plus Fostamatinib for the Treatment of Steroid Refractory Chronic Graft Versus Host Disease
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is an open-label phase I study of fostamatinib in combination with ruxolitinib for the treatment of chronic GvHD with a suboptimal response to corticosteroids The primary objective is to identify a minimum safe and biologically effective dose of fostamatinib when combined with standard of care ruxolitinib for the treatment of steroid refractory and steroid dependent cGVHD The secondary objective is to estimate the efficacy of the combination of ruxolitinib and fostamatinib for the treatment of steroid refractory and steroid dependent cGVHD
The target enrollment is 24-30 subjects The study will begin with an initial dose escalation cohort employing a modified 33 design to investigate up to three doses of fostamatinib Using safety efficacy pharmacodynamic PD and pharmacokinetic data PK an interim assessment will be performed to determine two candidate doses of the biologically optimal dose to investigate further A safety expansion cohort will be opened to backfill these two candidate doses up to a total 12 patients per dose including those in the dose escalation cohort who received the candidate doses Patients will then be randomized to one of these two candidate doses in the expansion If there is an imbalance in the two expansion cohorts the remaining patient slots after 11 randomization will be sequentially backfilled to a total of 12 patients per cohort A final analysis of safety efficacy and PKPD data in patients who received the two candidate doses will be conducted to determine a minimum safety and biologically effective dose which will be the recommended phase II dose RP2D
The primary hypothesis is that Fostamatinib combined with ruxolitinib is a safe therapy for and has synergistic activity in cGvHD The recommended phase II dose will be determined by the study investigators in collaboration with the sponsors The decision to select the recommended phase II dose will occur only after all patients in the part 1 have completed at least 28 days of therapy The decision will be based on the valuation of all relevant available data and not solely on dose-limiting toxicities
The target enrollment is 24-30 subjects The study will begin with an initial dose escalation cohort employing a modified 33 design to investigate up to three doses of fostamatinib Using safety efficacy pharmacodynamic PD and pharmacokinetic data PK an interim assessment will be performed to determine two candidate doses of the biologically optimal dose to investigate further A safety expansion cohort will be opened to backfill these two candidate doses up to a total 12 patients per dose including those in the dose escalation cohort who received the candidate doses Patients will then be randomized to one of these two candidate doses in the expansion If there is an imbalance in the two expansion cohorts the remaining patient slots after 11 randomization will be sequentially backfilled to a total of 12 patients per cohort A final analysis of safety efficacy and PKPD data in patients who received the two candidate doses will be conducted to determine a minimum safety and biologically effective dose which will be the recommended phase II dose RP2D
The primary hypothesis is that Fostamatinib combined with ruxolitinib is a safe therapy for and has synergistic activity in cGvHD The recommended phase II dose will be determined by the study investigators in collaboration with the sponsors The decision to select the recommended phase II dose will occur only after all patients in the part 1 have completed at least 28 days of therapy The decision will be based on the valuation of all relevant available data and not solely on dose-limiting toxicities
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None