Ruxolitinib Plus Fostamatinib for Steroid Refractory cGvHD
- Conditions
- Chronic Graft Versus Host Disease
- Interventions
- Registration Number
- NCT06233110
- Lead Sponsor
- Stefanie Sarantopoulos, MD, PhD.
- 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 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 te expansion. 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 30
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose escalation phase: Dose level 0 Fostamatinib Fostamatinib at dose level 0 (dose of 50mg QAM) in combination with standard of care ruxolitinib 10mg BID Dose escalation phase: Dose level 0 Ruxolitinib Fostamatinib at dose level 0 (dose of 50mg QAM) in combination with standard of care ruxolitinib 10mg BID Dose escalation phase: Dose level 3 Ruxolitinib Fostamatinib at dose level 3 (dose of 100mg BID) in combination with standard of care ruxolitinib 10mg BID Dose escalation phase: Dose level 2 Ruxolitinib Fostamatinib at dose level 2 (dose of 150mg QAM) in combination with standard of care ruxolitinib 10mg BID Candidate Dose #1 Fostamatinib 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. Dose escalation phase: Dose level 1 Ruxolitinib Fostamatinib at dose level 1 (dose of 100mg QAM) in combination with standard of care ruxolitinib 10mg BID Dose escalation phase: Dose level 1 Fostamatinib Fostamatinib at dose level 1 (dose of 100mg QAM) in combination with standard of care ruxolitinib 10mg BID Dose escalation phase: Dose level 2 Fostamatinib Fostamatinib at dose level 2 (dose of 150mg QAM) in combination with standard of care ruxolitinib 10mg BID Dose escalation phase: Dose level 3 Fostamatinib Fostamatinib at dose level 3 (dose of 100mg BID) in combination with standard of care ruxolitinib 10mg BID Candidate Dose #1 Ruxolitinib 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. Candidate Dose #2 Fostamatinib 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. Candidate Dose #2 Ruxolitinib 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 Measures
Name Time Method Minimum safe and biologically effective dose 6 months Minimum safe and biologically effective dose will be determined by dose limiting toxicities and overall response rate of the combination regimen, as well as pharmacokinetic and pharmacodynamic markers of fostamatinib (if available)
- Secondary Outcome Measures
Name Time Method Overall response rate 6 months Overall response rate, as defined by achievement of a complete response (CR) or partial response (PR), using the 2014 NIH Consensus criterion, during the first 6 months of therapy.
Duration of Response 1 year The length of time that a patient's response to treatment lasts.
1-year cGvHD-free survival 1 year The cGVHD-free survival is a composite endpoint that measures survival free from the diagnosis of chronic GVHD at any stage. cGvHD activity assessment includes medical history, physical exam, and laboratory studies per the 2014 NIH Consensus Response Criteria.
Overall survival 1 year The length of time that a patient lives following treatment.
Trial Locations
- Locations (1)
Duke
🇺🇸Durham, North Carolina, United States