T-cell Based Immunotherapy for of Melanoma

• ClinicalTrials.gov Identifier: NCT00937625
• Recruitment Status: Completed
• First Posted: July 13, 2009
• Last Update Posted: August 18, 2015
• Sponsor: Inge Marie Svane
• Information provided by (Responsible Party): Inge Marie Svane, Herlev Hospital

Tracking Information

• First Submitted Date: July 10, 2009
• First Posted Date: July 13, 2009
• Last Update Posted Date: August 18, 2015
• Study Start Date: June 2009
• Actual Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 10, 2009): toxicity [ Time Frame: week 0 to 20 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 10, 2009)

• immune response [ Time Frame: week 0 to 20 ]
• tumor response [ Time Frame: week 8 and every 3rd week until progression ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: T-cell Based Immunotherapy for of Melanoma
• Official Title: T-cell Based Immunotherapy for Treatment of Patients With Disseminated Melanoma.

Brief Summary

The aim of this study is to investigate the toxicity and clinical response of therapy with tumor infiltrating lymphocytes as treatment for advanced melanoma.

Patient will receive a single treatment consisting of conditioning chemotherapy for seven days (cyclophosphamide for two days and fludarabine for five days), intravenous infusion of high number of in vitro expanded tumor infiltrating lymphocytes followed by two weeks with daily low-dose interleukine-2. Patients will be evaluated for toxicity, tumor response, and immune response.

After the first 6 patients the treatment with IL-2 has been changed to include higher doses of IL-2 (see intervention)

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Melanoma

Intervention

Biological: cyclophosphamide, fludarabine, T-cells, Interleukin-2

Two days of cyclophosphamide (60 mg/kg i.v.) and five days of fludarabine (25 mg/m2 i.v.). Infusion of Tumor Infiltrating Lymphocytes (10e9-10e10 cells). Followed by daily sc injections of 2 MIE Interleukin-2 for two weeks. After the first 6 patients the dose of IL-2 has been changed to an i.v. decrescendo regimen using 18 MIU/m2 infused over 6, 12 and 24 hours and then 4.5 MIU/m2 infused over 24 hours for three days.

Other Names:

• Cyclophosphamide, Sendoxan®, Baxter A/S
• Fludarabine, Fludara®, Bayer Shering
• Interleukin-2, Proleukin®, Chiron B.V.

• Study Arms: Not Provided

Publications *

• Borch TH, Andersen R, Ellebaek E, Met Ö, Donia M, Marie Svane I. Future role for adoptive T-cell therapy in checkpoint inhibitor-resistant metastatic melanoma. J Immunother Cancer. 2020 Jul;8(2). pii: e000668. doi: 10.1136/jitc-2020-000668.
• Andersen R, Donia M, Ellebaek E, Borch TH, Kongsted P, Iversen TZ, Hölmich LR, Hendel HW, Met Ö, Andersen MH, Thor Straten P, Svane IM. Long-Lasting Complete Responses in Patients with Metastatic Melanoma after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and an Attenuated IL2 Regimen. Clin Cancer Res. 2016 Aug 1;22(15):3734-45. doi: 10.1158/1078-0432.CCR-15-1879. Epub 2016 Mar 22.
• Donia M, Hansen M, Sendrup SL, Iversen TZ, Ellebæk E, Andersen MH, Straten Pt, Svane IM. Methods to improve adoptive T-cell therapy for melanoma: IFN-γ enhances anticancer responses of cell products for infusion. J Invest Dermatol. 2013 Feb;133(2):545-52. doi: 10.1038/jid.2012.336. Epub 2012 Sep 27.
• Ellebaek E, Iversen TZ, Junker N, Donia M, Engell-Noerregaard L, Met Ö, Hölmich LR, Andersen RS, Hadrup SR, Andersen MH, thor Straten P, Svane IM. Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients. J Transl Med. 2012 Aug 21;10:169. doi: 10.1186/1479-5876-10-169.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 22, 2013): 31
• Original Estimated Enrollment (submitted: July 10, 2009): 6
• Actual Study Completion Date: January 2015
• Actual Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients with histological proven skin derived progressive metastatic or locally advanced malignant melanoma. Further inclusion criteria: Performance Status 0 to 1, surgical available metastasis, at least one measurable lesion, acceptable CBC and blood chemistry results. Acceptable organ functions.

Exclusion Criteria:

• Patients with a history of any other malignancies less than five years ago. Brain metastases. Other significant illness including severe allergy, asthma, DM, angina pectoris, congestive heart failure, chronic infections, or active autoimmune disease. Treatment with immune suppressive drugs, experimental drugs, or antineoplastic drugs.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Denmark

Administrative Information

• NCT Number: NCT00937625
• Other Study ID Numbers: MM0909
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Inge Marie Svane, Herlev Hospital
• Study Sponsor: Inge Marie Svane
• Collaborators: Not Provided

Investigators

• Study Director: Inge Marie Svane, Professor, MD; Department of Oncology, Copenhagen University Hospital, Herlev, Herlev Ringvej 75, DK-2730 Herlev, Denmark
• Principal Investigator: Rikke Andersen, MD; Center for Cancer Immune Therapy, department of Oncology, Herlev Hospital, Denmark

• PRS Account: Herlev Hospital
• Verification Date: August 2015