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

Official title

A Phase II b Study of Axatilimab in Combination With Extracorporeal Photopheresis (ECP) in Chronic Graft-versus-Host Disease

Overview

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).

Interventions

• Biological Axatilimab
  Axatilimab will be administered intravenously (IV) at a dose of 0.3 mg/kg, beginning as a pre-phase dose two weeks prior to initiation of Extracorporeal Photopheresis (ECP) therapy. Thereafter, Axatilimab will be administered with a frequency of one treatment session bi-weekly during each treatment cycle.
• Procedure Extracorporeal Photopheresis
  Mandatory ECP therapy will be administered at a frequency of two treatment sessions per week during Cycles 1 through 3, two treatment bi-weekly during Cycles 4 through 6, and two treatments during week 1 of Cycle 7. Optional ECP therapy will be administered at a frequency of two treatment sessions during weeks 2 and 4 of Cycles 4 through 6, when mandatory ECP is not administered. Optional ECP therapy will also be administered as two treatment sessions during week 3 of Cycle 7. After Cycle 7, p

Primary outcome measures

• Best Overall Response Rate (ORR) [Time frame: Up to 24 weeks]

Secondary outcome measures (8)

• Proportion of participants experiencing treatment-related adverse events (AEs) [Time frame: Up to 15 months]
• Proportion of participants experiencing serious adverse events (SAEs) [Time frame: Up to 15 months]
• Change in cumulative dose of corticosteroid usage [Time frame: Baseline, 24 weeks, 1 year]
• Duration of response (DOR) [Time frame: Up to 15 months]
• Relapse-free survival (RFS) [Time frame: Up to 15 months]
• Change in Quality of life (QoL) as measured by the modified Lee Symptom Scale (mLSS) score [Time frame: Baseline, 24 weeks, 1 year]
• Proportion of participants who develop subsequent sclerotic skin disease [Time frame: Up to 15 months]
• Rate of Complete Response (CR) at Best Response [Time frame: Up to 24 weeks]

Eligibility criteria

Inclusion criteria

• Recipient of allogeneic hematopoietic cell transplantation (HCT).
• Age greater or equal to 12.
• 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:

• 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.
• 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.
• 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.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-3 as assessed at Screening.
• Platelet count > 50,000 platelets/μL and absolute neutrophil count > 1,000 cells/μL as measured at Screening.
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN), unless attributed to presumed cGVHD as measured at Screening.
• Stable dose of corticosteroids for at least 14 days prior to treatment.
• 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

• Pregnancy or breast-feeding.
• Active relapse of underlying malignancy.
• History or the presence of interstitial pneumonitis or drug-related pneumonitis.
• Active gastrointestinal (GI) bleeding.
• Inability to tolerate volume shifts associated with ECP (e.g., inadequate renal, hepatic, pulmonary and cardiac function (ejection fraction (EF) < 40%) per Investigator discretion.
• History of myositis.
• History of splenectomy.
• History of pancreatitis.
• History of other malignancy (within 3 years of Screening) unless treated with curative intent and approved by Principal Investigator (PI).
• Significant, uncontrolled, or active comorbid conditions or are unable to adhere to the study requirements.
• Acquired Immune Deficiency Syndrome (AIDS) or active hepatitis B (Hep B) or active hepatitis C (Hep C) infection.
• Prior colony-stimulating factor-1 (CSF-1R) targeted therapies.
• Prior history of ECP treatment failure or intolerance.
• Intolerance to methoxsalen, heparin, or citrate products.
• Patients with aphakia due to risk of increased retinal damage or photosensitive disease (albinism, systemic lupus erythematosus, porphyria).
• Lack of stable IV access. Acceptable forms include central venous catheter, peripherally inserted central catheter (PICC), or peripheral IV line per institutional guidelines.
• Insurance denial of coverage for the ECP procedure.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 3 centers

• University of California, San Francisco — San Francisco
• University of Miami — Miami
• Ann & Robert H. Lurie Children's Hospital of Chicago — Chicago

Identifiers

NCT: NCT06663722 · 20240116

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗