Actively Recruiting
Ruxolitinib Plus Fostamatinib for Steroid Refractory cGvHD
Led by Stefanie Sarantopoulos, MD, PhD. · Updated on 2026-01-22
30
Participants Needed
1
Research Sites
191 weeks
Total Duration
On this page
Sponsors
S
Stefanie Sarantopoulos, MD, PhD.
Lead Sponsor
I
Incyte Corporation
Collaborating Sponsor
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
Ruxolitinib Plus Fostamatinib for Steroid Refractory cGvHD
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Able and willing to provide written informed consent before any study procedures
- Aged 18 years or older at the time of consent
- Have had an allogeneic hematopoietic cell transplant from any donor source
- Adequate bone marrow function with neutrophils ≥ 750/mm3, platelets ≥ 40,000/mm3, and hemoglobin ≥ 8.0 g/dL without transfusions
- Diagnosed with mild to severe chronic graft versus host disease (cGvHD) according to NIH criteria
- Confirmed steroid refractory or steroid dependent cGvHD with disease progression or persistence despite prednisone treatment
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
You will not qualify if you...
- Prior or ongoing ruxolitinib treatment for cGvHD longer than 3 weeks before study start
- Previous treatment with fostamatinib or another SYK inhibitor for GVHD
- Current systemic therapy for cGvHD beyond corticosteroids, calcineurin inhibitors, or mycophenolate mofetil, except less than 3 weeks of ruxolitinib
- Relapsed primary malignancy or treatment for relapse after transplant
- cGvHD occurring after unscheduled donor lymphocyte infusion for malignancy
- History of progressive multifocal leukoencephalopathy (PML)
- Active uncontrolled bacterial, fungal, parasitic, or viral infections
- Active viral diseases including HIV, CMV, HHV-6, HBV, HCV, or BK virus
- On mechanical ventilation or resting oxygen saturation below 90%
- Uncontrolled significant cardiovascular disease or recent major cardiovascular events
- Uncontrolled hypertension with systolic >160 mmHg or diastolic >100 mmHg
- Severe kidney impairment with creatinine clearance below 15 mL/min and not on dialysis
- Elevated liver enzymes or bilirubin beyond specified limits
- QTc interval ≥ 470 ms
- Active pregnancy, breastfeeding, or seeking pregnancy
- Any condition that may prevent compliance with study procedures
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
Duke
Durham, North Carolina, United States, 27710
Actively Recruiting
Research Team
C
Chenyu Lin, MD
CONTACT
L
Lauren Hill, BS
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
SINGLE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
6
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here