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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 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.
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Inclusion and exclusion criteria
Inclusion Criteria
Patient is able and willing to provide written informed consent prior to any study related screening procedures are performed.
Age ≥ 18 years old at the time of informed consent
Have undergone allogeneic HCT from any donor source (matched unrelated donor, sibling, haploidentical) using bone marrow, peripheral blood, or cord blood stem cells.
Adequate bone marrow function defined as:
Patients with clinically diagnosed cGvHD staging of mild to severe according to NIH Consensus Criteria prior to Cycle 1 Day 1, and who have confirmed corticosteroid dependence or refractoriness irrespective of the concomitant use of a calcineurin inhibitor, as follows:
Patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Exclusion Criteria
Primary purpose
Allocation
Interventional model
Masking
30 participants in 6 patient groups
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Central trial contact
Lauren Hill, BS; Chenyu Lin, MD
Data sourced from clinicaltrials.gov
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