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Peginterferon and TIL Therapy for Metastatic Melanoma

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ClinicalTrials.gov Identifier: NCT02379195
Recruitment Status : Active, not recruiting
First Posted : March 4, 2015
Last Update Posted : March 19, 2018
Sponsor:
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
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
Study Start Date : November 2014
Actual Primary Completion Date : January 2018
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine

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 and type of reported 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 ]
    To evaluate the immunological impact of peginterferon in combination with TIL therapy

  2. Objective response rate [ Time Frame: Up to 12 months ]
    Clinical responses will be evaluated by RECIST 1.1

  3. Overall survival [ Time Frame: Up to 12 months ]
    Overall survival (OS), defined as time from treatment initiation to death, will be described with use of Kaplan Meier curve

  4. Progression free survival [ Time Frame: Up to 12 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 Kaplan Meier curve.



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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
Criteria

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 ClinicalTrials.gov identifier (NCT number): NCT02379195


Locations
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Denmark
Center for Cancer Immune Therapy, Dept. of Haematology/Oncology
Copenhagen, Herlev, Denmark, 2730
Sponsors and Collaborators
Inge Marie Svane
Investigators
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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

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Responsible Party: Inge Marie Svane, Prof., MD, Herlev Hospital
ClinicalTrials.gov Identifier: NCT02379195     History of Changes
Other Study ID Numbers: MM1413
First Posted: March 4, 2015    Key Record Dates
Last Update Posted: March 19, 2018
Last Verified: March 2018
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Peginterferon alfa-2b
Interferon-alpha
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Interleukin-2
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents