Ruxolitinib Plus Fostamatinib for Steroid Refractory cGvHD

Launched by STEFANIE SARANTOPOULOS, MD, PHD. · Jan 22, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a combination of two medications, ruxolitinib and fostamatinib, to see if they can help patients with chronic graft-versus-host disease (cGvHD) who haven't responded well to steroid treatments. cGvHD is a condition that can occur after a stem cell transplant, where the new immune cells attack the patient's body. The researchers aim to find a safe and effective dose of fostamatinib to use alongside ruxolitinib, which is already a standard treatment for this condition.

To be eligible for this trial, patients must be at least 18 years old and have undergone a stem cell transplant. They should also have cGvHD that is either not responding to steroids or requiring them continuously. Participants will receive one of the two doses of fostamatinib identified during the study, and their health will be monitored closely for safety and effectiveness. The trial is not yet recruiting, but once it starts, it will include about 24 to 30 patients. If you or someone you know might be interested, it's important to discuss it with a healthcare provider to see if they meet the criteria for participation.

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Eligibility criteria

• • Inclusion Criteria
• • 1. Patient is able and willing to provide written informed consent prior to any study related screening procedures are performed.
• • 2. Age ≥ 18 years old at the time of informed consent
• • 3. Have undergone allogeneic hematopoietic cell transplantation (HCT) from any donor source (matched unrelated donor, sibling, haploidentical) using bone marrow, peripheral blood, or cord blood stem cells.
• 4. Adequate bone marrow function defined as:
• • 4.1 Absolute neutrophil count (ANC) ≥ 750 /mm3 4.2 Platelet count ≥ 40,000 /mm3 4.3 Hemoglobin ≥ 8.0 g/dL without transfusion support Note: Use of growth factor supplementation (myeloid, erythroid or megakaryocytic) is permitted to meet eligibility criteria.
• 5. Patients with clinically diagnosed cGvHD staging of mild to severe according to NIH Consensus Criteria4 prior to Cycle 1 Day 1 and with confirmed steroid refractoriness or steroid dependence irrespective of the concomitant use of a calcineurin inhibitor, as follows:
• • 5.1 Disease progression after administration of a minimum dose of 1.0 mg/kg/day or equivalent for at least 1 week at any time following diagnosis of cGvHD OR 5.2 Disease persistence despite continued treatment with prednisone \> 0.5mg/kg/d or equivalent for at least 4 weeks OR 5.3 Increase to prednisone \> 0.25 mg/kg/d after 1 unsuccessful attempt to taper the dose.
• • 5.4 Recurrence of chronic GVHD after attaining a complete response 5.5 Progression of chronic GVHD after attaining a partial response
• • 6. Patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• • Exclusion Criteria
• • 1. Prior or ongoing treatment with ruxolitinib for treatment of cGvHD for longer than 3 weeks prior to anticipated C1D1.
• • 2. Prior treatment with fostamatinib or another SYK inhibitor for the treatment of acute or chronic GVHD. Prior use of fostamatinib for conditions other than GVHD is permitted.
• • 3. Ongoing systemic therapy for cGvHD other than corticosteroids, calcineurin inhibitor, or mycophenolate mofetil, aside from fewer than 3 weeks of ruxolitinib. Prior ruxolitinib use for the indication of acute GVHD is permitted.
• • 4. Patients with relapsed primary malignancy, or who have been treated for relapse after the allogeneic HCT was performed
• • 5. SR-cGvHD occurring after a non-scheduled donor lymphocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence. Patients who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible.
• • 6. History of progressive multifocal leuko-encephalopathy (PML)
• • 7. Active uncontrolled bacterial, fungal, parasitic, or viral infection. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of infection progression are present.
• • 8. Clinical evidence of active and clinically significant viral disease including HIV, CMV, HHV-6, HBV, HCV, or BK virus.
• • 9. Patients on mechanical ventilation or have a resting O2 saturation \< 90% by pulse oximetry
• • 10. Clinically significant and uncontrolled cardiovascular disease, including unstable angina, acute myocardial infarction, or stroke within 3 months, or NYHA Class III or IV congestive heart failure.
• • 11. Uncontrolled hypertension with systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg.
• • 12. Creatinine clearance by Cockcroft-Gault of \< 15 mL/min and not on dialysis
• • 13. Total bilirubin \> 3 times ULN, ALT \> 5 times ULN, or AST \> 5 times ULN
• • 14. QTc ≥ 470 ms as calculated by the Fridericia Formula
• • 15. Active pregnancy or breast feeding, or currently seeking active pregnancy
• • 16. Any patient who, in the opinion of the investigator, may not be able to comply with study procedures