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Peginterferon and TIL Therapy for Metastatic Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02379195
Recruitment Status : Completed
First Posted : March 4, 2015
Results First Posted : January 22, 2020
Last Update Posted : January 22, 2020
Information provided by (Responsible Party):
Inge Marie Svane, Herlev Hospital

Brief Summary:

Adoptive T cell therapy with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. The TILs are isolated from the patients own tumor tissue followed by in vitro expansion and activation for around 4-6 weeks. Before TIL infusion the patients receive 1 week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After TIL infusion Interleukin-2 are administered to support T cell activation and proliferation in vivo.

In this trial the therapy is combined with peginterferon (the pegylated form of interferon alpha 2b). Interferon alpha has immunomodulatory effects and is known to upregulate HLA expression on melanoma cells and are hypothesized to synergize with TIL therapy.

Condition or disease Intervention/treatment Phase
Metastatic Melanoma Drug: Cyclophosphamide Drug: Fludarabine Biological: TIL infusion Drug: Interleukin-2 Drug: Peginterferon alfa-2b Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: T Cell Therapy in Combination With Peginterferon for Patients With Metastatic Melanoma
Actual Study Start Date : November 2014
Actual Primary Completion Date : January 2018
Actual Study Completion Date : October 2018

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: A

All patients receive the same treatment.

All patients are hospitalized during treatment (approximately 3 weeks) and receive treatment only once.

The patients are admitted to hospital day -8 and receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine) on day -7 to day -1.

The TILs are infused on day 0 and Interleukin-2 therapy are administered on day 0 to day 5.

Interleukin-2 are administered in an i.v. continuous decrescendo regimen starting approximately 6 hours after TIL infusion with a duration of approximately 5 days

Subcutaneous injections of peginterferon alpha 2b are administered three time (day -2, day 7 and day 14)

Drug: Cyclophosphamide
Cyclophosphamide 60 mg/kg are administered i.v on day -7 and -6

Drug: Fludarabine
Fludarabine 25 mg/m2 are administered i.v on day -5 to -1
Other Names:
  • Fludarabinephosphate
  • Fludara

Biological: TIL infusion
The maximum number of expanded TILs are infused over 30-45 min on day 0
Other Name: T cell infusion

Drug: 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)
Other Names:
  • IL-2
  • Proleukin

Drug: Peginterferon alfa-2b
Peginterferon alpha-2b, 3 microgram/kg are administered as subcutaneous injection on day -2, day 7 and day 14.
Other Name: PegIntron

Primary Outcome Measures :
  1. Number of Participants With Adverse Events/Serious Adverse Events [ Time Frame: 0-24 weeks ]
    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

Secondary Outcome Measures :
  1. Treatment Related Immune Responses [ Time Frame: Up to 12 months ]
    Number of participants with detectable in vitro immune responses in the TIL infusion product using intracellular flow cytometry.

  2. Objective Response Rate [ Time Frame: Up to 36 months ]
    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

  3. Overall Survival [ Time Frame: Up to 36 months ]
    Overall survival (OS), defined as time from treatment initiation to death, described using the Kaplan Meier method

  4. Progression Free Survival [ Time Frame: Up to 36 months ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Histologically confirmed unresectable stage III or stage IV metastatic melanoma Metastasis available for surgical resection (about 2 cm3) and residual measurable disease after resection

ECOG performance status 0-1

Life expectancy ≥ 3 months

No significant toxicity from prior treatments

Adequate renal, hepatic and hematologic function

Women of childbearing potential (WOCBP) and men in a sexual relationship with a WOCBP must be using an effective method of contraception during treatment and for at least 6 months after completion af treatment.

Able to comprehend the information given and willing to sign informed consent


Exclusion Criteria:

Other Malignancies, unless followed for ≥ 5 years with no sign of disease, except squamous cell carcinoma or adequately treated carcinoma in situ colli uteri.

Cerebral metastasis. Patients with previously treated CNS metastases can participate if CNS metastases are surgically removed or treated with stereotactic radiosurgery and stable ≥ 28 days after treatment measured by MRI. Patients with asymptomatic, stable and untreated CNS metastasis can in be included according to investigators and sponsors decision.

Patients with ocular melanoma

Severe allergies, history of anaphylaxis or known allergies to the administered drugs.

Serious medical or psychiatric comorbidity

Creatinine clearance < 70 ml/min

Acute or chronic infection with e.g. HIV, hepatitis, tuberculosis

Severe and active autoimmune disease

Pregnant and nursing women

Need for immunosuppressive treatment, e.g. corticosteroids or methotrexate

Concomitant treatment with other experimental drugs

Patients with uncontrolled hypercalcemia

Less than four weeks since prior systemic antineoplastic treatment at the time of treatment.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02379195

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Center for Cancer Immune Therapy, Dept. of Haematology/Oncology
Copenhagen, Herlev, Denmark, 2730
Sponsors and Collaborators
Inge Marie Svane
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Study Director: Inge Marie Svane, Prof, PhD, MD Center for Cancer Immune Therapy, Dept of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730 Herlev, Denmark
Principal Investigator: Rikke Andersen, MD Center for Cancer Immune Therapy, Dept of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730 Herlev, Denmark
  Study Documents (Full-Text)

Documents provided by Inge Marie Svane, Herlev Hospital:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Inge Marie Svane, Prof., MD, Herlev Hospital Identifier: NCT02379195    
Other Study ID Numbers: MM1413
First Posted: March 4, 2015    Key Record Dates
Results First Posted: January 22, 2020
Last Update Posted: January 22, 2020
Last Verified: January 2020
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Peginterferon alfa-2b
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Antiviral Agents
Anti-Infective Agents