Trial Outcomes & Findings for Peginterferon and TIL Therapy for Metastatic Melanoma (NCT NCT02379195)
NCT ID: NCT02379195
Last Updated: 2020-01-22
Results Overview
Determine the safety of the administration of peginterferon in combination with TIL therapy including lymphodepleting chemotherapy and Interleukin-2 by reporting adverse events according to CTCAE v. 4.0
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
12 participants
Primary outcome timeframe
0-24 weeks
Results posted on
2020-01-22
Participant Flow
All patients were recruited from Danish melanoma centers.
Participant milestones
| Measure |
Arm A: TIL + IFNalpha
The patients are admitted to hospital day -8 and receive lymphodepleting chemotherapy with cyclophosphamide 60 mg/kg on day -7 and -6 and fludarabine 25 mg/m2 on day -5 to day -1.
TIL infusion: The maximum number of expanded TILs are infused over 30-45 min on day 0
Interleukin-2: Interleukin-2 are administered as a continuous i.v. infusion in a decrescendo regimen (18 MIU/m2 IL-2 over 6 hours, 18 MIU/m2 IL-2 over 12 hours, 18 MIU IL-2 over 24 hours followed by 4.5 MIU/m2 IL-2 over another 24 hours for three days)
Peginterferon alfa-2b: Peginterferon alpha-2b, 3 microgram/kg are administered as subcutaneous injection on day -2, day 7 and day 14.
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|---|---|
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Overall Study
STARTED
|
12
|
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Overall Study
COMPLETED
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12
|
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Arm A: TIL + IFNalpha
n=12 Participants
The patients are admitted to hospital day -8 and receive lymphodepleting chemotherapy with cyclophosphamide 60 mg/kg on day -7 and -6 and fludarabine 25 mg/m2 on day -5 to day -1.
TIL infusion: The maximum number of expanded TILs are infused over 30-45 min on day 0
Interleukin-2: Interleukin-2 are administered as a continuous i.v. infusion in a decrescendo regimen (18 MIU/m2 IL-2 over 6 hours, 18 MIU/m2 IL-2 over 12 hours, 18 MIU IL-2 over 24 hours followed by 4.5 MIU/m2 IL-2 over another 24 hours for three days)
Peginterferon alfa-2b: Peginterferon alpha-2b, 3 microgram/kg are administered as subcutaneous injection on day -2, day 7 and day 14.
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|---|---|
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Age, Continuous
|
57 years
n=12 Participants
|
|
Sex: Female, Male
Female
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6 Participants
n=12 Participants
|
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Sex: Female, Male
Male
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6 Participants
n=12 Participants
|
|
Region of Enrollment
Denmark
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12 participants
n=12 Participants
|
PRIMARY outcome
Timeframe: 0-24 weeksPopulation: 12 patients were treated with TIL.
Determine the safety of the administration of peginterferon in combination with TIL therapy including lymphodepleting chemotherapy and Interleukin-2 by reporting adverse events according to CTCAE v. 4.0
Outcome measures
| Measure |
Arm A: TIL + IFNalpha
n=12 Participants
The patients are admitted to hospital day -8 and receive lymphodepleting chemotherapy with cyclophosphamide 60 mg/kg on day -7 and -6 and fludarabine 25 mg/m2 on day -5 to day -1.
TIL infusion: The maximum number of expanded TILs are infused over 30-45 min on day 0
Interleukin-2: Interleukin-2 are administered as a continuous i.v. infusion in a decrescendo regimen (18 MIU/m2 IL-2 over 6 hours, 18 MIU/m2 IL-2 over 12 hours, 18 MIU IL-2 over 24 hours followed by 4.5 MIU/m2 IL-2 over another 24 hours for three days)
Peginterferon alfa-2b: Peginterferon alpha-2b, 3 microgram/kg are administered as subcutaneous injection on day -2, day 7 and day 14.
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|---|---|
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Number of Participants With Adverse Events/Serious Adverse Events
Adverse events
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12 Participants
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|
Number of Participants With Adverse Events/Serious Adverse Events
Treatment-related adverse events
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12 Participants
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|
Number of Participants With Adverse Events/Serious Adverse Events
Serious adverse events
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4 Participants
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SECONDARY outcome
Timeframe: Up to 12 monthsNumber of participants with detectable in vitro immune responses in the TIL infusion product using intracellular flow cytometry.
Outcome measures
| Measure |
Arm A: TIL + IFNalpha
n=12 Participants
The patients are admitted to hospital day -8 and receive lymphodepleting chemotherapy with cyclophosphamide 60 mg/kg on day -7 and -6 and fludarabine 25 mg/m2 on day -5 to day -1.
TIL infusion: The maximum number of expanded TILs are infused over 30-45 min on day 0
Interleukin-2: Interleukin-2 are administered as a continuous i.v. infusion in a decrescendo regimen (18 MIU/m2 IL-2 over 6 hours, 18 MIU/m2 IL-2 over 12 hours, 18 MIU IL-2 over 24 hours followed by 4.5 MIU/m2 IL-2 over another 24 hours for three days)
Peginterferon alfa-2b: Peginterferon alpha-2b, 3 microgram/kg are administered as subcutaneous injection on day -2, day 7 and day 14.
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|---|---|
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Treatment Related Immune Responses
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6 Participants
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SECONDARY outcome
Timeframe: Up to 36 monthsPopulation: 12 patients were treated with TIL. 1 patient was not evaluable.
Clinical responses will be evaluated by RECIST 1.1 (Response Criteria In Solid Tumors Criteria version 1.1) and assessed by CT scan. Complete response (CR), disapperance of all lesions; Partial response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Objective response (OR) = CR + PR
Outcome measures
| Measure |
Arm A: TIL + IFNalpha
n=11 Participants
The patients are admitted to hospital day -8 and receive lymphodepleting chemotherapy with cyclophosphamide 60 mg/kg on day -7 and -6 and fludarabine 25 mg/m2 on day -5 to day -1.
TIL infusion: The maximum number of expanded TILs are infused over 30-45 min on day 0
Interleukin-2: Interleukin-2 are administered as a continuous i.v. infusion in a decrescendo regimen (18 MIU/m2 IL-2 over 6 hours, 18 MIU/m2 IL-2 over 12 hours, 18 MIU IL-2 over 24 hours followed by 4.5 MIU/m2 IL-2 over another 24 hours for three days)
Peginterferon alfa-2b: Peginterferon alpha-2b, 3 microgram/kg are administered as subcutaneous injection on day -2, day 7 and day 14.
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|---|---|
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Objective Response Rate
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2 Participants
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SECONDARY outcome
Timeframe: Up to 36 monthsPopulation: 12 patients were treated with TIL. 1 patient was not evaluable.
Overall survival (OS), defined as time from treatment initiation to death, described using the Kaplan Meier method
Outcome measures
| Measure |
Arm A: TIL + IFNalpha
n=11 Participants
The patients are admitted to hospital day -8 and receive lymphodepleting chemotherapy with cyclophosphamide 60 mg/kg on day -7 and -6 and fludarabine 25 mg/m2 on day -5 to day -1.
TIL infusion: The maximum number of expanded TILs are infused over 30-45 min on day 0
Interleukin-2: Interleukin-2 are administered as a continuous i.v. infusion in a decrescendo regimen (18 MIU/m2 IL-2 over 6 hours, 18 MIU/m2 IL-2 over 12 hours, 18 MIU IL-2 over 24 hours followed by 4.5 MIU/m2 IL-2 over another 24 hours for three days)
Peginterferon alfa-2b: Peginterferon alpha-2b, 3 microgram/kg are administered as subcutaneous injection on day -2, day 7 and day 14.
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|---|---|
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Overall Survival
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11.75 months
Interval 0.13 to 27.33
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SECONDARY outcome
Timeframe: Up to 36 monthsPopulation: 12 patients were treated with TIL. 1 patient was not evaluable.
Progression free survival (PFS), defined as the time from treatment initiation to disease progression, relapse or death due to any cause, which ever comes first, will be described with the Kaplan Meier method.
Outcome measures
| Measure |
Arm A: TIL + IFNalpha
n=11 Participants
The patients are admitted to hospital day -8 and receive lymphodepleting chemotherapy with cyclophosphamide 60 mg/kg on day -7 and -6 and fludarabine 25 mg/m2 on day -5 to day -1.
TIL infusion: The maximum number of expanded TILs are infused over 30-45 min on day 0
Interleukin-2: Interleukin-2 are administered as a continuous i.v. infusion in a decrescendo regimen (18 MIU/m2 IL-2 over 6 hours, 18 MIU/m2 IL-2 over 12 hours, 18 MIU IL-2 over 24 hours followed by 4.5 MIU/m2 IL-2 over another 24 hours for three days)
Peginterferon alfa-2b: Peginterferon alpha-2b, 3 microgram/kg are administered as subcutaneous injection on day -2, day 7 and day 14.
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|---|---|
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Progression Free Survival
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2.8 months
Interval 0.13 to 18.4
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Adverse Events
Arm A: TIL + IFNalpha
Serious events: 4 serious events
Other events: 12 other events
Deaths: 8 deaths
Serious adverse events
| Measure |
Arm A: TIL + IFNalpha
n=12 participants at risk
The patients are admitted to hospital day -8 and receive lymphodepleting chemotherapy with cyclophosphamide 60 mg/kg on day -7 and -6 and fludarabine 25 mg/m2 on day -5 to day -1.
TIL infusion: The maximum number of expanded TILs are infused over 30-45 min on day 0
Interleukin-2: Interleukin-2 are administered as a continuous i.v. infusion in a decrescendo regimen (18 MIU/m2 IL-2 over 6 hours, 18 MIU/m2 IL-2 over 12 hours, 18 MIU IL-2 over 24 hours followed by 4.5 MIU/m2 IL-2 over another 24 hours for three days)
Peginterferon alfa-2b: Peginterferon alpha-2b, 3 microgram/kg are administered as subcutaneous injection on day -2, day 7 and day 14.
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|---|---|
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Respiratory, thoracic and mediastinal disorders
Respiratory distress
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8.3%
1/12 • Number of events 1 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
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8.3%
1/12 • Number of events 1 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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Ear and labyrinth disorders
Vertigo
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8.3%
1/12 • Number of events 1 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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Gastrointestinal disorders
Mucositis
|
8.3%
1/12 • Number of events 1 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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Blood and lymphatic system disorders
Platelet count decreased
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8.3%
1/12 • Number of events 1 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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Blood and lymphatic system disorders
Bone marrow hypocellular
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8.3%
1/12 • Number of events 1 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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Other adverse events
| Measure |
Arm A: TIL + IFNalpha
n=12 participants at risk
The patients are admitted to hospital day -8 and receive lymphodepleting chemotherapy with cyclophosphamide 60 mg/kg on day -7 and -6 and fludarabine 25 mg/m2 on day -5 to day -1.
TIL infusion: The maximum number of expanded TILs are infused over 30-45 min on day 0
Interleukin-2: Interleukin-2 are administered as a continuous i.v. infusion in a decrescendo regimen (18 MIU/m2 IL-2 over 6 hours, 18 MIU/m2 IL-2 over 12 hours, 18 MIU IL-2 over 24 hours followed by 4.5 MIU/m2 IL-2 over another 24 hours for three days)
Peginterferon alfa-2b: Peginterferon alpha-2b, 3 microgram/kg are administered as subcutaneous injection on day -2, day 7 and day 14.
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|---|---|
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Blood and lymphatic system disorders
Febrile neutropenia
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100.0%
12/12 • Number of events 12 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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Infections and infestations
Infection
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58.3%
7/12 • Number of events 7 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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General disorders
Fatique
|
100.0%
12/12 • Number of events 12 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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Gastrointestinal disorders
Nausea
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100.0%
12/12 • Number of events 12 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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Gastrointestinal disorders
Vomiting
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66.7%
8/12 • Number of events 8 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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Gastrointestinal disorders
Diarrhea
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91.7%
11/12 • Number of events 11 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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Gastrointestinal disorders
Constipation
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50.0%
6/12 • Number of events 6 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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|
Gastrointestinal disorders
Oral mucositis
|
50.0%
6/12 • Number of events 6 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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Skin and subcutaneous tissue disorders
Rash, maculo-papular
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50.0%
6/12 • Number of events 6 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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Musculoskeletal and connective tissue disorders
Myalgia
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66.7%
8/12 • Number of events 8 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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Respiratory, thoracic and mediastinal disorders
Dyspnea
|
100.0%
12/12 • Number of events 12 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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Respiratory, thoracic and mediastinal disorders
Pulmonary edema
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8.3%
1/12 • Number of events 1 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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Cardiac disorders
Atrial fibrillation
|
8.3%
1/12 • Number of events 1 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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Blood and lymphatic system disorders
Petechia
|
33.3%
4/12 • Number of events 4 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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Nervous system disorders
Confusion
|
50.0%
6/12 • Number of events 6 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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Ear and labyrinth disorders
Hearing impairment
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41.7%
5/12 • Number of events 5 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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Investigations
Hypophosphatemia
|
8.3%
1/12 • Number of events 1 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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General disorders
alopecia
|
100.0%
11/11 • Number of events 11 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
|
|
Eye disorders
Anterior uveitis
|
8.3%
1/12 • Number of events 1 • Adverse events were collected from starting treatment until 24 weeks after TIL infusion.
Adverse events were recorded in open-ended discussion and through scoring of adverse events according to AE recording forms by the treating physician.
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Additional Information
Dr. Inge Marie Svane
Center for Cancer Immune Therapy, Herlev Hospital
Phone: 38683868
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place