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

Phase 2

Recruiting

• Conditions: Chronic Graft Versus Host Disease; cGVHD
• Interventions: Biological: Axatilimab; Procedure: Extracorporeal Photopheresis

• Registration Number: NCT06663722
• Lead Sponsor: University of Miami

Brief Summary

The purpose of this study is to see whether giving participants a combination treatment of Axatilimab and Extracorporeal Photopheresis (ECP) is effective against chronic Graft-versus-Host Disease (cGVHD).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-10-26
• Study First Submitted QC: 2024-10-26
• Study First Posted: 2024-10-29
• Status Verified: 2025-05
• Study Start: 2025-05-05
• Last Update Submitted: 2025-05-16
• Last Update Posted: 2025-05-20
• Primary Completion: 2030-05-05
• Study Completion: 2030-05-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 49

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Axatilimab in combination with ECP Group	Axatilimab	Participants in this group will receive Axatilimab in combination with extracorporeal photopheresis (ECP) therapy for up to seven (7) four-week cycles. Total participation duration is about 15 months.
Axatilimab in combination with ECP Group	Extracorporeal Photopheresis	Participants in this group will receive Axatilimab in combination with extracorporeal photopheresis (ECP) therapy for up to seven (7) four-week cycles. Total participation duration is about 15 months.

Primary Outcome Measures

Name	Time	Method
Best Overall Response Rate (ORR)	Up to 24 weeks	Best overall response rate (ORR) will be reported as the percentage of participants who achieve partial response (PR) or a complete response (CR) to study therapy, as defined by the 2014 National Institutes of Health (NIH) Consensus Development Project on Criteria for Clinical Trials in chronic graft-versus-host disease (cGVHD) while on study treatment.

Secondary Outcome Measures

Name	Time	Method
Proportion of participants experiencing serious adverse events (SAEs)	Up to 15 months	Proportion of participants experiencing serious adverse events (SAEs) will be reported, regardless of attribution to study treatment, as determined by the treating physician. SAEs will be assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
Change in cumulative dose of corticosteroid usage	Baseline, 24 weeks, 1 year	Change in cumulate dose corticosteroid usage among study participants will be reported, from baseline to 24 weeks and to 1-year post start of Axatilimab. Corticosteroid dosage, recorded as average dose in mg per day, will be recorded at each interval.
Duration of response (DOR)	Up to 15 months	Duration of response (DOR) is defined as the elapsed time in months from best response (partial response (PR) or complete response (CR)) to documented progression of chronic graft-versus-host disease (cGVHD), start of new therapy, or death for any reason.
Relapse-free survival (RFS)	Up to 15 months	Relapse-free survival (RFS) is defined as the elapsed time in months from the date of the first dose of study treatment to relapse or recurrence of the primary hematologic malignancy or disorder or death.
Proportion of participants experiencing treatment-related adverse events (AEs)	Up to 15 months	Proportion of participants experiencing treatment-related adverse events (AEs) will be reported. AEs, including serious adverse events (SAEs), will be assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Attribution of AEs and SAEs to study treatment will be reported as possibly, probably and definitely related, as determined by the treating physician.
Change in Quality of life (QoL) as measured by the modified Lee Symptom Scale (mLSS) score	Baseline, 24 weeks, 1 year	Changes in quality of life (QoL) from baseline, as measured by the modified Lee Symptom Scale (mLSS) score questionnaire, will be estimated at 24 weeks and 1 year and reported. The mLSS is a 30-item self-reported questionnaire, with seven (7) subscales (skin, eyes, mouth, lung, nutrition, energy and psych) containing 2-7 items which allow calculation of a summary score. Each item uses a 5-point Likert scale ranging from 0 points ("Not at all"/"No symptoms") to 4 points ("Extremely"/"Very severe"). Lower scores indicate improved quality of life. An improvement in \> 5-points is considered clinically significant.
Proportion of participants who develop subsequent sclerotic skin disease	Up to 15 months	The proportion of participants who develop subsequent sclerotic skin disease in those who present without such manifestations will be reported.
Rate of Complete Response (CR) at Best Response	Up to 24 weeks	The rate of complete response (CR) at best response will be reported as the percentage of patients who achieve CR at best response, as defined by the 2014 National Institutes of Health (NIH) Consensus Development Project on Criteria for Clinical Trials in chronic graft-versus-host disease (cGVHD) while on study treatment.

Trial Locations

Locations (1)

University of Miami; 🇺🇸 Miami, Florida, United States