Ruxolitinib Plus Fostamatinib for Steroid Refractory cGvHD

Part of paid clinical trials in Durham, North Carolina.

Sponsor
Stefanie Sarantopoulos, MD, PhD.
Study ID
NCT06233110
Phase
PHASE1
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 80 Years
Healthy Volunteers
Not accepted

Interventions

  • Fostamatinib — DRUG
    Fostamatinib will be administered as part of the initial dose escalation cohort and then two candidate doses will be identified to be administered for the safety expansion cohort.
  • Ruxolitinib — DRUG
    Ruxolitinib 10mg BID will be administered in combination with Fostamatinib in each of the study arms.

Study Details

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 3+3 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 1:1 randomization will be sequentially backfilled to a total of 12 patients per cohort. A final analysis of safety, efficacy, and PK/PD 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.

Key Dates

Start date
Oct 29, 2025
Status verified
Jan 2026
Primary completion
Jan 1, 2029
Completion
Jul 1, 2029

Study Design

Enrollment
30 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Dose escalation phase: Dose level 0
    Fostamatinib at dose level 0 (dose of 50mg QAM) in combination with standard of care ruxolitinib 10mg BID
  • Experimental: Dose escalation phase: Dose level 1
    Fostamatinib at dose level 1 (dose of 100mg QAM) in combination with standard of care ruxolitinib 10mg BID
  • Experimental: Dose escalation phase: Dose level 2
    Fostamatinib at dose level 2 (dose of 150mg QAM) in combination with standard of care ruxolitinib 10mg BID
  • Experimental: Dose escalation phase: Dose level 3
    Fostamatinib at dose level 3 (dose of 100mg BID) in combination with standard of care ruxolitinib 10mg BID
  • Experimental: Candidate Dose #1
    In the safety expansion cohort, subjects will be randomized to one of two candidate doses of fostamatinib (identified from the dose escalation phase) in combination with ruxolitinib 10mg BID.
  • Experimental: Candidate Dose #2
    In the safety expansion cohort, subjects will be randomized to one of two candidate doses of fostamatinib (identified from the dose escalation phase) in combination with ruxolitinib 10mg BID.

Primary Outcome Measure

Minimum safe and biologically effective dose [ Time Frame: 6 months ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
DukeDurhamNorth Carolina27710
Chenyu Lin

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By research site
Duke· Durham, NC

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