Peginterferon and TIL Therapy for Metastatic Melanoma

NCT02379195 | Completed Phase 1 Results DMC

• 1 other identifier: MM1413
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Melanoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Treatment Related Immune Responses

  Up to 12 months

• Objective Response Rate

  Up to 36 months

• Overall Survival

  Up to 36 months

• Progression Free Survival

  Up to 36 months

Study Arms (1)

A

EXPERIMENTAL

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; Drug: Fludarabine; Biological: TIL infusion; Drug: Interleukin-2; Drug: Peginterferon alfa-2b

Interventions

Cyclophosphamide DRUG

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

A

Fludarabine DRUG

Fludarabine 25 mg/m2 are administered i.v on day -5 to -1

Also known as: Fludarabinephosphate, Fludara

A

TIL infusion BIOLOGICAL

The maximum number of expanded TILs are infused over 30-45 min on day 0

Also known as: T cell infusion

A

Interleukin-2 DRUG

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)

Also known as: IL-2, Proleukin

A

Peginterferon alfa-2b DRUG

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

Also known as: PegIntron

A

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Inge Marie Svane: lead

Study Sites (1)

Center for Cancer Immune Therapy, Dept. of Haematology/Oncology

Copenhagen, Herlev, 2730, Denmark

Location

Related Publications (1)

• Borch TH, Andersen R, Ellebaek E, Met O, Donia M, Svane IM. Future role for adoptive T-cell therapy in checkpoint inhibitor-resistant metastatic melanoma. J Immunother Cancer. 2020 Jul;8(2):e000668. doi: 10.1136/jitc-2020-000668.

  PMID: 32747469 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Interleukin-2; aldesleukin; peginterferon alfa-2b

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Limitations and Caveats

Only twelve patients were treated.

Results Point of Contact

• Title: Dr. Inge Marie Svane
• Organization: Center for Cancer Immune Therapy, Herlev Hospital

inge.marie.svane@regionh.dk

38683868

Study Officials

• 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

  STUDY DIRECTOR

• Rikke Andersen, MD

  Center for Cancer Immune Therapy, Dept of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730 Herlev, Denmark

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof., MD

Study Record Dates

• First Submitted: February 27, 2015
• First Posted: March 4, 2015
• Study Start: November 1, 2014
• Primary Completion: January 1, 2018
• Study Completion: October 1, 2018
• Last Updated: January 22, 2020
• Results First Posted: January 22, 2020

Record last verified: 2020-01

Locations

DK (1)