Peginterferon and TIL Therapy for Metastatic Melanoma

Metastatic Melanoma Clinical Trial

Official title:

T Cell Therapy in Combination With Peginterferon for Patients With Metastatic Melanoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02379195
• Other study ID #: MM1413
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 2014
• Est. completion date: October 2018

Study information

• Verified date: January 2020
• Source: Herlev Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: October 2018
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

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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.

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Related Conditions & MeSH terms

• Melanoma
• Metastatic Melanoma

Intervention

Drug:
• Cyclophosphamide
Cyclophosphamide 60 mg/kg are administered i.v on day -7 and -6
• Fludarabine
Fludarabine 25 mg/m2 are administered i.v on day -5 to -1

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

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)
• Peginterferon alfa-2b
Peginterferon alpha-2b, 3 microgram/kg are administered as subcutaneous injection on day -2, day 7 and day 14.

Locations

Country	Name	City	State
Denmark	Center for Cancer Immune Therapy, Dept. of Haematology/Oncology	Copenhagen	Herlev

Sponsors (1)

Lead Sponsor	Collaborator
Inge Marie Svane

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events/Serious Adverse Events	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	0-24 weeks
Secondary	Treatment Related Immune Responses	Number of participants with detectable in vitro immune responses in the TIL infusion product using intracellular flow cytometry.	Up to 12 months
Secondary	Objective Response Rate	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	Up to 36 months
Secondary	Overall Survival	Overall survival (OS), defined as time from treatment initiation to death, described using the Kaplan Meier method	Up to 36 months
Secondary	Progression Free Survival	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.	Up to 36 months