Extracorporeal Photopheresis for Bronchiolitis Obliterans Syndrome

(ECP Trial)

Not currently recruiting at 22 trial locations

Overseen By Mary Clare Derfler, RN, MSN

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Washington University School of Medicine

Must not be taking: T lymphocyte depleting

Disqualifiers: Pregnancy, Lupus, Porphyria, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 24

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment called Extracorporeal Photopheresis (ECP) for individuals with Bronchiolitis Obliterans Syndrome (BOS), a condition that can develop after a lung transplant. The study aims to determine if ECP can benefit those whose BOS hasn't improved with other treatments or those newly diagnosed. Participants will receive either ECP or standard care to compare outcomes. It suits individuals who have had a lung transplant, are on Medicare, and have a diagnosis of BOS with ongoing lung function decline despite previous treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are currently participating in another clinical trial or using certain investigational agents, you may be excluded from this study.

What prior data suggests that Extracorporeal Photopheresis is safe for treating Bronchiolitis Obliterans Syndrome?

Research has shown that Extracorporeal Photopheresis (ECP) is generally well-tolerated by patients with bronchiolitis obliterans syndrome (BOS), particularly those unresponsive to treatments like azithromycin. Studies have found promising results with ECP in managing this condition, and no major safety issues have been reported. Additionally, Medicare covers ECP for BOS treatment, indicating confidence in its safety. While ECP is being tested specifically for BOS, its approval for other conditions suggests it is safe for patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Bronchiolitis Obliterans Syndrome?

Researchers are excited about extracorporeal photopheresis (ECP) for bronchiolitis obliterans syndrome (BOS) because it offers a unique approach compared to traditional treatments like immunosuppressive agents. Unlike these standard options, ECP works by modifying immune cells outside the body, potentially reducing inflammation and slowing disease progression without the side effects commonly associated with long-term immunosuppression. This method is particularly appealing because it targets the immune response more precisely, offering hope for patients with refractory BOS who don't respond well to existing treatments.

What evidence suggests that Extracorporeal Photopheresis might be an effective treatment for Bronchiolitis Obliterans Syndrome?

Studies have shown that Extracorporeal Photopheresis (ECP) can effectively treat Bronchiolitis Obliterans Syndrome (BOS), especially in patients unresponsive to standard treatments like azithromycin. In this trial, participants with newly diagnosed BOS will be randomized to receive either early ECP intervention or standard care. Meanwhile, those with refractory BOS will be assigned to either ECP treatment or observation based on specific criteria. Research indicates that ECP may improve lung function, measured by the forced expiratory volume in one second (FEV1), a key indicator of breathing ability. Patients receiving ECP have experienced better survival rates after lung transplants, suggesting a positive impact on long-term health. Additionally, ECP has been linked to a slower decline in lung function, offering hope for those with this challenging condition. Overall, these findings support the potential effectiveness of ECP for treating BOS. ^{1 2 4 6 7}

Who Is on the Research Team?

George Despotis, MD

Principal Investigator

Washington University St. Louis School of Medicine

Are You a Good Fit for This Trial?

This trial is for Medicare recipients aged 18 or older who have had a lung transplant and are diagnosed with Bronchiolitis Obliterans Syndrome (BOS). They must have documented declines in lung function, frequent spirometry tests, and no history of certain cancers or conditions that would affect the study. Pregnant individuals, those allergic to ECP treatment components, or currently in another BOS clinical trial cannot participate.

Inclusion Criteria

I have been diagnosed with BOS, showing a significant decline in lung function.

I have received a lung transplant.

Medicare-eligible status

Exclusion Criteria

You have a condition that may make it hard for you to do breathing tests.

I have not had ECP therapy in the last 6 months.

My BOS developed either before 2016 or after 2022.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Extracorporeal Photopheresis (ECP) treatment for Bronchiolitis Obliterans Syndrome (BOS). Newly diagnosed BOS patients are randomized to either ECP or standard care.

6 months

24 treatments over 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with spirometry every 30 days for the first year and then annually.

Up to December 2028

Annual visits

Long-term Follow-up

Participants are followed for long-term outcomes, including mortality and quality of life assessments.

Annually up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Extracorporeal Photopheresis (ECP)

Trial Overview

The study is testing Extracorporeal Photopheresis (ECP) effectiveness on patients with either refractory BOS—those not responding to treatments—or newly diagnosed BOS after lung transplantation. It aims to collect data on how well these patients respond to ECP as per Medicare requirements.

How Is the Trial Designed?

Group I: Standard of Care Comparator Retrospective Chart review Experimental Treatment 1 Intervention

Data for the SOC comparator will be obtained via a retrospective data capture mechanism either medical chart review or electronic medical record query that meet all of the inclusion criteria and through an IRB approved waiver of consent. The SOC comparator data will be identical to the data collected for the Refractory BOS patients with the exception of inclusion of all spirometry values after transplant.

Group II: Refractory Bronchiolitis Obliterans Syndrome (REFRACTORY BOS) Experimental Treatment 1 Intervention

Participants with REFRACTORY BOS will be electronically assigned to either ECP treatment or Observation based on the participant's pre-enrollment Forced Expiratory Volume in 1 second (FEV1). Values from pulmonary function tests from the preceding 12 months will be entered into a web-based treatment allocation which will perform an automated calculation. Patients who have a statistically significant rate of decline within the preceding 6 months, and a derived protocol defined slope, will be assigned to the ECP Treatment arm. If a patient does not meet these criteria, the participant will be assigned to the Observation arm. Two hundred and fifty-eight (258) participants were enrolled with Refractory BOS nationwide.

Group III: Newly Diagnosed Bronchiolitis Obliterans (NEW BOS) Experimental Treatment 1 Intervention

Participants with NEW BOS will be randomized to Early Photopheresis Intervention (EPI) or Control (Standard of Care). EPI patients will receive 24 treatments in a 6-month period and may continue maintenance treatments. Twenty-two (22) NEW BOS participants were enrolled nationwide. The Control group will receive local Standard of Care for the management of BOS. Therapy will involve changes in immunosuppressive agents.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Therakos, Inc

Collaborator

Centers for Medicare and Medicaid Services/ Coverage and Analysis Group

Collaborator

Trials

2

Recruited

9,000+

The Foundation for Barnes-Jewish Hospital

Collaborator

Trials

43

Recruited

6,600+

Mallinckrodt

Industry Sponsor

Trials

202

Recruited

15,700+

Mario Saltarelli

Mallinckrodt

Chief Medical Officer

MD

Siggi Olafsson

Mallinckrodt

Chief Executive Officer

PhD in Pharmacy

Centers for Medicare and Medicaid Services

Collaborator

Trials

41

Recruited

31,230,000+

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/29557913/

Extracorporeal Photopheresis for Bronchiolitis Obliterans ...

Extracorporeal photopheresis (ECP) has shown promising results in patients who develop BOS refractory to azithromycin treatment.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02181257

NCT02181257 | Extracorporeal Photopheresis for ...

The primary aims of this study is to determine the efficacy and tolerability of Extracorporeal Photopheresis (ECP) for the treatment of either Refractory ...

3.

journals.lww.com

journals.lww.com/transplantjournal/fulltext/2018/07000/extracorporeal_photopheresis_for_bronchiolitis.14.aspx

Extracorporeal Photopheresis for Bronchiolitis Obliterans...

Extracorporeal photopheresis (ECP) has shown promising results in patients who develop BOS refractory to azithromycin treatment.

4.

cms.gov

cms.gov/medicare/coverage/evidence/lung-transplant

Extracorporeal Photopheresis for Bronchiolitis Obliterans ...

improved forced expiratory volume in one second (FEV1), or decreased rate of decline of FEV1;; improved survival after transplant; and/or ...

5.

frontierspartnerships.org

frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2023.11551/full

A European Multi-Center Analysis of Extracorporeal ...

The primary endpoint was patient survival after initiation of ECP. This study included 631 patients, 87% suffered from bronchiolitis obliterans ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7228625/

Extracorporeal Photopheresis for Bronchiolitis Obliterans ...

Extracorporeal photopheresis (ECP) has shown promising results in patients who develop BOS refractory to azithromycin treatment.

7.

jhltonline.org

jhltonline.org/article/S1053-2498(12)01107-2/fulltext

A prospective interventional study on the use of ...

The aim of this prospective study was to evaluate the efficacy and safety of extracorporeal photopheresis (ECP) in patients with bronchiolitis obliterans ...