Trial Outcomes & Findings for Methoxsalen and Extracorporeal Photopheresis (ECP) for the Treatment of Pediatric Participants With Steroid Refractory Acute Graft Versus Host Disease (NCT NCT02524847)
NCT ID: NCT02524847
Last Updated: 2020-09-11
Results Overview
OR using the modified IBMTR Severity Index is defined as complete response (CR) + partial response (PR) as follows: * CR: complete resolution of all signs and symptoms of aGvHD in all evaluable organs without addition of next-line systemic treatment * PR: improvement of 1 stage in 1 or more aGvHD target organs without progression in others and without addition of next-line systemic treatment
TERMINATED
PHASE3
29 participants
4 weeks
2020-09-11
Participant Flow
Participants were recruited by multiple treatment centers in the United States and Europe
Participant milestones
| Measure |
Methoxsalen With ECP
Participants receive methoxsalen 20 µg/ml in conjunction with extracorporeal photopheresis (ECP) procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
|
|---|---|
|
Overall Study
STARTED
|
29
|
|
Overall Study
Completed Treatment Up to Week 12
|
14
|
|
Overall Study
Started Second Line Treatment
|
5
|
|
Overall Study
COMPLETED
|
15
|
|
Overall Study
NOT COMPLETED
|
14
|
Reasons for withdrawal
| Measure |
Methoxsalen With ECP
Participants receive methoxsalen 20 µg/ml in conjunction with extracorporeal photopheresis (ECP) procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
|
|---|---|
|
Overall Study
Adverse Event
|
4
|
|
Overall Study
Unsatisfactory Therapeutic Effect
|
4
|
|
Overall Study
Condition no Longer Requires Treatment
|
4
|
|
Overall Study
Death
|
1
|
|
Overall Study
Reason not Specified
|
1
|
Baseline Characteristics
Methoxsalen and Extracorporeal Photopheresis (ECP) for the Treatment of Pediatric Participants With Steroid Refractory Acute Graft Versus Host Disease
Baseline characteristics by cohort
| Measure |
Methoxsalen With ECP
n=29 Participants
Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
|
|---|---|
|
Age, Continuous
|
8.6 years
STANDARD_DEVIATION 5.02 • n=99 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
24 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
2 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
White
|
22 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Other
|
4 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 4 weeksPopulation: All participants
OR using the modified IBMTR Severity Index is defined as complete response (CR) + partial response (PR) as follows: * CR: complete resolution of all signs and symptoms of aGvHD in all evaluable organs without addition of next-line systemic treatment * PR: improvement of 1 stage in 1 or more aGvHD target organs without progression in others and without addition of next-line systemic treatment
Outcome measures
| Measure |
Methoxsalen With ECP
n=29 Participants
Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
|
|---|---|
|
Number of Participants Achieving Overall Response (OR) Using the Modified International Bone Marrow Transplant Registry (IBMTR) Severity Index at Week 4
|
16 Participants
|
SECONDARY outcome
Timeframe: 16 weeksPopulation: All participants
Clinically significant changes in vital signs, laboratory values and investigations are reported as adverse events. Summary data are provided below, with details listed in the adverse events module.
Outcome measures
| Measure |
Methoxsalen With ECP
n=29 Participants
Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
|
|---|---|
|
Number of Participants With Adverse Events
Death for any cause
|
3 Participants
|
|
Number of Participants With Adverse Events
Any serious AE
|
12 Participants
|
|
Number of Participants With Adverse Events
Non-serious TEAE at 5% threshold
|
17 Participants
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: Evaluable Participants (Participants with appropriate efficacy data at the given time point)
OR using the modified IBMTR Severity Index is defined as complete response (CR) + partial response (PR) as follows: * CR: complete resolution of all signs and symptoms of aGvHD in all evaluable organs without addition of next-line systemic treatment * PR: improvement of 1 stage in 1 or more aGvHD target organs without progression in others and without addition of next-line systemic treatment
Outcome measures
| Measure |
Methoxsalen With ECP
n=19 Participants
Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
|
|---|---|
|
Percentage of Participants Achieving Overall Response (OR) Using Modified IBMTR Severity Index at Week 8
|
73.7 percentage of participants
Interval 48.8 to 90.9
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Evaluable Participants (Participants with appropriate efficacy data at the given time point)
OR using the modified IBMTR Severity Index is defined as complete response (CR) + partial response (PR) as follows: * CR: complete resolution of all signs and symptoms of aGvHD in all evaluable organs without addition of next-line systemic treatment * PR: improvement of 1 stage in 1 or more aGvHD target organs without progression in others and without addition of next-line systemic treatment
Outcome measures
| Measure |
Methoxsalen With ECP
n=14 Participants
Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
|
|---|---|
|
Percentage of Participants Achieving Overall Response (OR) Using Modified IBMTR Severity Index at Week 12
|
78.6 percentage of participants
Interval 49.2 to 95.3
|
SECONDARY outcome
Timeframe: 16 weeksPopulation: Population meeting the criterion
Duration of first response is presented for patients whose disease progressed. Duration of response is defined in the following way: Patients whose response failed: Date at which 1st disease progression occurs - date of 1st response +1. Patients whose response did not relapse: Date of 16 week follow-up or final assessment prior to week 16 (if patient withdrew early) - date of 1st response.
Outcome measures
| Measure |
Methoxsalen With ECP
n=18 Participants
Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
|
|---|---|
|
Duration of Response (Days) Within 16 Weeks Using Modified IBMTR Severity Index
|
13.5 days
Interval 4.0 to 50.0
|
SECONDARY outcome
Timeframe: 4 weeks, 8 weeks, and 12 weeksPopulation: All participants with a score at the given time point
ORR is defined as the percentage of patients who achieve an overall response after 4 weeks, 8 weeks, and 12 weeks of ECP treatment according to a scoring algorithm applied to calculate the grade of aGvHD using the modified Glucksberg Criteria.
Outcome measures
| Measure |
Methoxsalen With ECP
n=29 Participants
Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
|
|---|---|
|
Overall Response Rate (ORR) According to the Modified Glucksberg Criteria
Week 4
|
50 percentage of participants
Interval 29.1 to 70.9
|
|
Overall Response Rate (ORR) According to the Modified Glucksberg Criteria
Week 8
|
63.2 percentage of participants
Interval 38.4 to 83.7
|
|
Overall Response Rate (ORR) According to the Modified Glucksberg Criteria
Week 12
|
78.6 percentage of participants
Interval 49.2 to 95.3
|
SECONDARY outcome
Timeframe: From diagnosis of aGvHD to 12 WeeksPopulation: All participants
Steroids administered from diagnosis of aGvHD to 12 Weeks after initiation of ECP treatment
Outcome measures
| Measure |
Methoxsalen With ECP
n=29 Participants
Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
|
|---|---|
|
Cumulative Dose of Daily Steroids
|
1917 mg
Interval 192.0 to 6895.0
|
SECONDARY outcome
Timeframe: at 4, 8 and 12 weeksPopulation: All participants with scores at the given time point
Number of patients whose skin was rated as Stage 0 - 4 using the modified Glucksberg criteria based on the Graft versus Host Disease (GvHD) rash - Stages are defined as 0=No GvHD rash, 1=Maculopapular rash on \<25% body surface area (BSA), 2=Maculopapular rash on 25-50% BSA, 3=Maculopapular rash on \>50% BSA, and 4=Generalized erythroderma plus bullous formation, which are blisters bigger than 5 mm across
Outcome measures
| Measure |
Methoxsalen With ECP
n=29 Participants
Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
|
|---|---|
|
Number of Patients With Skin Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 8 · Stage 1
|
5 Participants
|
|
Number of Patients With Skin Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 8 · Stage 2
|
1 Participants
|
|
Number of Patients With Skin Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 4 · Stage 0
|
9 Participants
|
|
Number of Patients With Skin Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 4 · Stage 1
|
8 Participants
|
|
Number of Patients With Skin Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 4 · Stage 2
|
3 Participants
|
|
Number of Patients With Skin Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 4 · Stage 3
|
3 Participants
|
|
Number of Patients With Skin Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 4 · Stage 4
|
0 Participants
|
|
Number of Patients With Skin Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 8 · Stage 0
|
11 Participants
|
|
Number of Patients With Skin Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 8 · Stage 3
|
1 Participants
|
|
Number of Patients With Skin Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 8 · Stage 4
|
0 Participants
|
|
Number of Patients With Skin Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 12 · Stage 0
|
10 Participants
|
|
Number of Patients With Skin Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 12 · Stage 1
|
2 Participants
|
|
Number of Patients With Skin Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 12 · Stage 2
|
1 Participants
|
|
Number of Patients With Skin Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 12 · Stage 3
|
1 Participants
|
|
Number of Patients With Skin Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 12 · Stage 4
|
0 Participants
|
SECONDARY outcome
Timeframe: at 4, 8 and 12 weeksPopulation: All participants with scores at the given time point
Number of patients whose liver was rated as Stage 0 - 4 on the modified Glucksberg criteria - Stages are based on level of bilirubin, defined as: Stage 0 = Bilirubin \< 2.0 mg/dL, Stage 1 = Bilirubin 2.0-3.0 mg/dL, Stage 2 = Bilirubin 3.1-6.0 mg/dL, Stage 3 = Bilirubin 6.1-15.0 mg/dL, and Stage 4 = Bilirubin \> 15.0 mg/dL
Outcome measures
| Measure |
Methoxsalen With ECP
n=29 Participants
Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
|
|---|---|
|
Number of Patients With Liver Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 4 · Stage 0
|
19 Participants
|
|
Number of Patients With Liver Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 12 · Stage 1
|
0 Participants
|
|
Number of Patients With Liver Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 4 · Stage 1
|
1 Participants
|
|
Number of Patients With Liver Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 4 · Stage 2
|
1 Participants
|
|
Number of Patients With Liver Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 4 · Stage 3
|
0 Participants
|
|
Number of Patients With Liver Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 4 · Stage 4
|
0 Participants
|
|
Number of Patients With Liver Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 8 · Stage 0
|
13 Participants
|
|
Number of Patients With Liver Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 8 · Stage 1
|
0 Participants
|
|
Number of Patients With Liver Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 8 · Stage 2
|
0 Participants
|
|
Number of Patients With Liver Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 8 · Stage 3
|
0 Participants
|
|
Number of Patients With Liver Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 8 · Stage 4
|
0 Participants
|
|
Number of Patients With Liver Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 12 · Stage 0
|
12 Participants
|
|
Number of Patients With Liver Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 12 · Stage 2
|
0 Participants
|
|
Number of Patients With Liver Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 12 · Stage 3
|
0 Participants
|
|
Number of Patients With Liver Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Week 12 · Stage 4
|
0 Participants
|
Adverse Events
Methoxsalen With ECP
Serious adverse events
| Measure |
Methoxsalen With ECP
n=29 participants at risk
Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
|
|---|---|
|
Infections and infestations
Aspergilloma
|
3.4%
1/29 • Up to 16 weeks
|
|
Infections and infestations
Bk virus infection
|
3.4%
1/29 • Up to 16 weeks
|
|
Infections and infestations
Cellulitis
|
3.4%
1/29 • Up to 16 weeks
|
|
Infections and infestations
Cystitis viral
|
3.4%
1/29 • Up to 16 weeks
|
|
Infections and infestations
Cytomegalovirus infection
|
3.4%
1/29 • Up to 16 weeks
|
|
Infections and infestations
Device related infection
|
3.4%
1/29 • Up to 16 weeks
|
|
Infections and infestations
Hepatitis E
|
3.4%
1/29 • Up to 16 weeks
|
|
General disorders
Pyrexia
|
6.9%
2/29 • Up to 16 weeks
|
|
General disorders
General physical health deterioration
|
3.4%
1/29 • Up to 16 weeks
|
|
Immune system disorders
Acute graft versus host disease
|
6.9%
2/29 • Up to 16 weeks
|
|
Immune system disorders
Acute graft versus host disease in intestine
|
3.4%
1/29 • Up to 16 weeks
|
|
Immune system disorders
Acute graft versus host disease in liver
|
3.4%
1/29 • Up to 16 weeks
|
|
Immune system disorders
Graft versus host disease
|
3.4%
1/29 • Up to 16 weeks
|
|
Blood and lymphatic system disorders
Autoimmune haemolytic anaemia
|
3.4%
1/29 • Up to 16 weeks
|
|
Blood and lymphatic system disorders
Pancytopenia
|
3.4%
1/29 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
3.4%
1/29 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
3.4%
1/29 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
3.4%
1/29 • Up to 16 weeks
|
|
Renal and urinary disorders
Cystitis haemorrhagic
|
3.4%
1/29 • Up to 16 weeks
|
|
Renal and urinary disorders
Renal failure
|
3.4%
1/29 • Up to 16 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.4%
1/29 • Up to 16 weeks
|
|
Nervous system disorders
Haemorrhage intracranial
|
3.4%
1/29 • Up to 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
3.4%
1/29 • Up to 16 weeks
|
|
Vascular disorders
Hypertension
|
3.4%
1/29 • Up to 16 weeks
|
Other adverse events
| Measure |
Methoxsalen With ECP
n=29 participants at risk
Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
13.8%
4/29 • Up to 16 weeks
|
|
Gastrointestinal disorders
Nausea
|
13.8%
4/29 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
10.3%
3/29 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
10.3%
3/29 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
6.9%
2/29 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
6.9%
2/29 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Malnutrition
|
6.9%
2/29 • Up to 16 weeks
|
|
Vascular disorders
Hypertension
|
13.8%
4/29 • Up to 16 weeks
|
|
Vascular disorders
Hypotension
|
10.3%
3/29 • Up to 16 weeks
|
|
Infections and infestations
Clostridium difficile infection
|
6.9%
2/29 • Up to 16 weeks
|
|
Infections and infestations
Cytomegalovirus infection
|
6.9%
2/29 • Up to 16 weeks
|
|
Infections and infestations
Pneumonia
|
6.9%
2/29 • Up to 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
13.8%
4/29 • Up to 16 weeks
|
|
General disorders
Pyrexia
|
10.3%
3/29 • Up to 16 weeks
|
|
Immune system disorders
Hypogammaglobulinaemia
|
10.3%
3/29 • Up to 16 weeks
|
|
Investigations
Immunoglobulins decreased
|
6.9%
2/29 • Up to 16 weeks
|
|
Psychiatric disorders
Depression
|
6.9%
2/29 • Up to 16 weeks
|
Additional Information
Medical Information Call Center
Mallinckrodt Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place