Peginterferon and TIL Therapy for Metastatic Melanoma

Back to results

Primary Purpose

Status

Completed

Phase

Phase 1

Locations

Denmark

Study Type

Interventional

Intervention

Cyclophosphamide

Fludarabine

TIL infusion

Interleukin-2

Peginterferon alfa-2b

About this trial

This is an interventional treatment trial for Metastatic Melanoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

-

Sites / Locations

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

A

Arm Description

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)

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Treatment Related Immune Responses

Number of participants with detectable in vitro immune responses in the TIL infusion product using intracellular flow cytometry.

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

Overall Survival

Overall survival (OS), defined as time from treatment initiation to death, described using the Kaplan Meier method

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.

Full Information

NCT ID

NCT02379195

First Posted

February 27, 2015

Last Updated

January 13, 2020

Sponsor

Inge Marie Svane

1. Study Identification

Unique Protocol Identification Number

NCT02379195

Brief Title

Peginterferon and TIL Therapy for Metastatic Melanoma

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2020

Overall Recruitment Status

Completed

Study Start Date

November 2014 (Actual)

Primary Completion Date

January 2018 (Actual)

Study Completion Date

October 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Inge Marie Svane

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Melanoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

A

Arm Type

Experimental

Arm Description

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)

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Fludarabine

Other Intervention Name(s)

Fludarabinephosphate, Fludara

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

TIL infusion

Other Intervention Name(s)

T cell infusion

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Interleukin-2

Other Intervention Name(s)

IL-2, Proleukin

Intervention Description

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)

Intervention Type

Drug

Intervention Name(s)

Peginterferon alfa-2b

Other Intervention Name(s)

PegIntron

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of Participants With Adverse Events/Serious Adverse Events

Description

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

Time Frame

0-24 weeks

Secondary Outcome Measure Information:

Title

Treatment Related Immune Responses

Description

Number of participants with detectable in vitro immune responses in the TIL infusion product using intracellular flow cytometry.

Time Frame

Up to 12 months

Title

Objective Response Rate

Description

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

Time Frame

Up to 36 months

Title

Overall Survival

Description

Overall survival (OS), defined as time from treatment initiation to death, described using the Kaplan Meier method

Time Frame

Up to 36 months

Title

Progression Free Survival

Description

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.

Time Frame

Up to 36 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

No

Eligibility 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. -

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Inge Marie Svane, Prof, PhD, MD

Organizational Affiliation

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

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Rikke Andersen, MD

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

Copenhagen

State/Province

Herlev

ZIP/Postal Code

2730

Country

Denmark

12. IPD Sharing Statement

Citations:

PubMed Identifier

32747469

Citation

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.

Results Reference

derived

Metastatic Melanoma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial