Axatilimab in Combination With Extracorporeal Photopheresis (ECP) in Chronic Graft-versus-Host Disease

Launched by UNIVERSITY OF MIAMI · Oct 26, 2024

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ClinConnect Summary

This clinical trial is studying a new treatment for chronic Graft-versus-Host Disease (cGVHD), a condition that can occur after a stem cell or bone marrow transplant. The researchers want to find out if a combination of two therapies, Axatilimab and Extracorporeal Photopheresis (ECP), can help improve symptoms in people who are not responding well to previous treatments. This trial is open to individuals aged 12 and older who have received a specific type of transplant and have been diagnosed with cGVHD that requires new therapy.

If you or a loved one qualify for this study, you can expect to receive the combination treatment and be closely monitored by the medical team. There are some important eligibility criteria: participants should have had at least two prior treatments for cGVHD, and they must have active symptoms that haven’t improved with steroid treatment. Additionally, individuals with certain health conditions or those who are pregnant or breastfeeding may not be eligible. The trial is not yet recruiting participants, but it's an opportunity for those who have struggled with cGVHD to potentially benefit from a new approach.

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Eligibility criteria

• Inclusion Criteria:
• • 1. Recipient of allogeneic hematopoietic cell transplantation (HCT).
• • 2. Age greater or equal to 12.
• 3. Chronic GVHD per 2014 National Institutes of Health Consensus Criteria (NCC) (Jagasia et al. 2015) or overlap syndrome requiring new therapy in patients with at least 2 prior lines of therapy, steroid refractoriness, or steroid dependence:
• • 1. Prior systemic lines of therapy may include corticosteroids, calcineurin inhibitor (CNI) or sirolimus, or other systemic immunosuppressive agent such as ruxolitinib, belumosudil, or ibrutinib. GVHD prophylaxis does not count as a prior line of therapy.
• 2. Steroid refractory is defined as any of the following criteria:
• • i. Manifestations progress despite the use of ≥ 1 mg/kg/day prednisone for at least 1 week
• • ii. Manifestations persist without improvement despite treatment with ≥ 0.5 mg/kg/day or 1 mg/kg every other day for at least four weeks.
• • iii. Recurrence after a CR, or
• • iv. Progression after a PR.
• • 3. Steroid dependence is defined as inability to control cGVHD symptoms while tapering prednisone below 0.25 mg/kg/day on at least two occasions separated by at least 8 weeks. There must be evidence of clinically active cGVHD.
• • 4. For patients receiving approved or commonly used agents, all GVHD systemic treatments should be discontinued except for corticosteroids and drugs being continued from GVHD prophylaxis at screening.
• • 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-3 as assessed at Screening.
• • 6. Platelet count \> 50,000 platelets/μL and absolute neutrophil count \> 1,000 cells/μL as measured at Screening.
• • 7. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN), unless attributed to presumed cGVHD as measured at Screening.
• • 8. Stable dose of corticosteroids for at least 14 days prior to treatment.
• • 9. Sexually mature individuals must use contraception as described in Section 4.12. For individuals less than 18 years of age, sexual maturity will be determined as per treating pediatrician.
• Exclusion Criteria:
• • 1. Pregnancy or breast-feeding.
• • 2. Active relapse of underlying malignancy.
• • 3. History or the presence of interstitial pneumonitis or drug-related pneumonitis.
• • 4. Active gastrointestinal (GI) bleeding.
• • 5. Inability to tolerate volume shifts associated with ECP (e.g., inadequate renal, hepatic, pulmonary and cardiac function (ejection fraction (EF) \< 40%) per Investigator discretion.
• • 6. History of myositis.
• • 7. History of splenectomy.
• • 8. History of pancreatitis.
• • 9. History of other malignancy (within 3 years of Screening) unless treated with curative intent and approved by Principal Investigator (PI).
• • 10. Significant, uncontrolled, or active comorbid conditions or are unable to adhere to the study requirements.
• • 11. Acquired Immune Deficiency Syndrome (AIDS) or active hepatitis B (Hep B) or active hepatitis C (Hep C) infection.
• • 12. Prior colony-stimulating factor-1 (CSF-1R) targeted therapies.
• • 13. Prior history of ECP treatment failure or intolerance.
• • 14. Intolerance to methoxsalen, heparin, or citrate products.
• • 15. Patients with aphakia due to risk of increased retinal damage or photosensitive disease (albinism, systemic lupus erythematosus, porphyria).
• • 16. Lack of stable IV access. Acceptable forms include central venous catheter, peripherally inserted central catheter (PICC), or peripheral IV line per institutional guidelines.
• • 17. Insurance denial of coverage for the ECP procedure.