Chronic Graft Versus Host Disease
Conditions
Keywords
Extracorporeal photopheresis therapy, Methoxsalen, cGVHD, hematopoietic stem cell transplantation
Brief summary
Chronic graft-versus-host disease (cGVHD) is a long-lasting complication that can occur after transplants. The transplanted cells seem to fight with the patient's own cells. Extracorporeal photopheresis (ECP) is a fairly new procedure for cGVHD. The participant gets a port to hook up to a machine. The machine removes the white blood cells, mixes them with a light-sensitive drug, shines light on it, and puts all the blood back in. This study will find out if patients respond better if they get ECP with methoxsalen, in addition to the pills normally used to treat cGVHD.
Detailed description
The investigation of extracorporeal photopheresis (ECP) plus standard of care (SoC) (SoC+ECP) in chronic graft-versus-host disease (cGVHD) within prospective, randomized clinical studies is limited, despite its frequent clinical use. This phase 1/pilot study was the first randomized, prospective study to investigate ECP use as first-line therapy in cGVHD, based on the 2015 National Institutes of Health (NIH) consensus criteria for diagnosis and response assessment. Adult patients with new-onset (≤3 years of hematopoietic stem cell transplantation) moderate or severe cGVHD were randomized 1:1 to 26 weeks of SoC+ECP vs SoC (corticosteroids and cyclosporine A/tacrolimus) between 2011 and 2015. The primary endpoint was overall response rate (ORR), defined as complete or partial response, at week 28 in the intention-to-treat population (ITT).
Interventions
DRUGECP Methoxsalen
Methoxsalen delivered by ECP
DRUGStandard of Care
Tapered prednisone with cyclosporine or tacrolimus via oral administration, consistent with local institutional practice (corticosteroids and cyclosporine A/tacrolimus)
Sponsors
Parexel
Mallinckrodt
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Pilot Study for the 2015 NIH Consensus Criteria to inform the design of subsequent studies
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
To be eligible for inclusion in this trial, the patient must have moderate to severe chronic graft-versus-host disease \[defined by the National Institutes of Health (NIH) 2015 Consensus Criteria\] that started within 3 years after hematopoietic stem cell transplantation (HSCT).
Exclusion criteria
* Is intolerant to corticosteroids or hypersensitive to methoxsalen * Received certain treatments during time periods disallowed by protocol * Has infections and/or requires treatment that (per protocol or in the opinion of the investigator) might compromise: 1. safety and well-being of participant or offspring 2. safety of study staff 3. analysis of results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With an Overall Response at Week 28 | Week 28 | Participants with overall response included those with partial response or complete response, according to study staff who did not know which treatment they received (blinded assessment). |
Countries
Austria, France, Germany, Hungary, Italy, Spain, United Kingdom, United States
Participant flow
Recruitment details
Patients were enrolled in Austria, France, Germany, Italy, Hungary, Spain, the United Kingdom, and the United States. Enrollment started in November 2011, and the last patient visit occurred in March 2015.
Pre-assignment details
All participants enrolled were included in the safety analysis set
Participants by arm
| Arm | Count |
|---|---|
| ECP Methoxsalen + SoC Participants receive ECP methoxsalen in addition to standard of care | 29 |
| Standard of Care (SOC) Participants receive only standard of care | 31 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 |
| Overall Study | Death | 3 | 0 |
| Overall Study | Lack of Efficacy | 0 | 3 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Study site closed | 0 | 5 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | ECP Methoxsalen + SoC | Total | Standard of Care (SOC) |
|---|---|---|---|
| Age, Customized 18-44 years | 8 Participants | 18 Participants | 10 Participants |
| Age, Customized 45-64 years | 19 Participants | 38 Participants | 19 Participants |
| Age, Customized 65 years and over | 2 Participants | 4 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 48 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 8 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Collected | 4 Participants | 10 Participants | 6 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 22 Participants | 46 Participants | 24 Participants |
| Region of Enrollment Austria | 3 participants | 6 participants | 3 participants |
| Region of Enrollment France | 4 participants | 10 participants | 6 participants |
| Region of Enrollment Germany | 11 participants | 18 participants | 7 participants |
| Region of Enrollment Hungary | 4 participants | 8 participants | 4 participants |
| Region of Enrollment Italy | 0 participants | 3 participants | 3 participants |
| Region of Enrollment Spain | 0 participants | 1 participants | 1 participants |
| Region of Enrollment United Kingdom | 1 participants | 2 participants | 1 participants |
| Region of Enrollment United States | 6 participants | 12 participants | 6 participants |
| Sex: Female, Male Female | 7 Participants | 20 Participants | 13 Participants |
| Sex: Female, Male Male | 22 Participants | 40 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 29 | 0 / 31 |
| other Total, other adverse events | 26 / 28 | 24 / 28 |
| serious Total, serious adverse events | 8 / 28 | 9 / 28 |
Outcome results
Primary
Number of Participants With an Overall Response at Week 28
Participants with overall response included those with partial response or complete response, according to study staff who did not know which treatment they received (blinded assessment).
Time frame: Week 28
Population: Intention to treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ECP Methoxsalen + SoC | Number of Participants With an Overall Response at Week 28 | 20 Participants |
| Standard of Care (SoC) | Number of Participants With an Overall Response at Week 28 | 14 Participants |
p-value: 0.373Fisher Exact