Ruxolitinib + Fostamatinib for Chronic Graft-versus-Host Disease

Recruiting in Palo Alto (17 mi)

Overseen byChenyu Lin, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Stefanie Sarantopoulos, MD, PhD.

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

Eligibility Criteria

This trial is for individuals with chronic Graft-versus-Host Disease (cGVHD) who haven't responded well to steroids. Participants should have specific conditions like Bronchiolitis Obliterans Syndrome and be able to receive both Ruxolitinib and Fostamatinib.

Inclusion Criteria

I have received a stem cell transplant from a donor.

I have chronic GvHD that's not responding well to steroids, regardless of other treatments.

Patient is able and willing to provide written informed consent prior to any study related screening procedures are performed

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Exclusion Criteria

I have had progressive multifocal leukoencephalopathy in the past.

I do not have any ongoing serious infections, or they are being treated and under control.

I do not have active significant viral infections like HIV or hepatitis.

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Treatment Details

Interventions

Fostamatinib (Other)
Ruxolitinib (Corticosteroid)

Trial OverviewThe study tests the safety and effectiveness of combining two drugs, Ruxolitinib and Fostamatinib, for cGVHD patients not responding to steroids. It starts by finding a safe dose before expanding to more patients who will help determine the best dose for future studies.

Participant Groups

6Treatment groups

Experimental Treatment

Group I: Dose escalation phase: Dose level 3Experimental Treatment2 Interventions

Fostamatinib at dose level 3 (dose of 100mg BID) in combination with standard of care ruxolitinib 10mg BID

Group II: Dose escalation phase: Dose level 2Experimental Treatment2 Interventions

Fostamatinib at dose level 2 (dose of 150mg QAM) in combination with standard of care ruxolitinib 10mg BID

Group III: Dose escalation phase: Dose level 1Experimental Treatment2 Interventions

Fostamatinib at dose level 1 (dose of 100mg QAM) in combination with standard of care ruxolitinib 10mg BID

Group IV: Dose escalation phase: Dose level 0Experimental Treatment2 Interventions

Fostamatinib at dose level 0 (dose of 50mg QAM) in combination with standard of care ruxolitinib 10mg BID

Group V: Candidate Dose #2Experimental Treatment2 Interventions

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.

Group VI: Candidate Dose #1Experimental Treatment2 Interventions

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.

Fostamatinib is already approved in United States for the following indications:

🇺🇸 Approved in United States as Tavalisse for: