T-cell Based Immunotherapy for of Melanoma

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ClinicalTrials.gov Identifier: NCT00937625

Recruitment Status : Completed

First Posted : July 13, 2009

Last Update Posted : August 18, 2015

Sponsor:

Information provided by (Responsible Party):

Inge Marie Svane, Herlev Hospital

Study Description

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)

Condition or disease	Intervention/treatment	Phase
Melanoma	Biological: cyclophosphamide, fludarabine, T-cells, Interleukin-2	Phase 1 Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	31 participants
Allocation:	N/A
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	T-cell Based Immunotherapy for Treatment of Patients With Disseminated Melanoma.
Study Start Date :	June 2009
Actual Primary Completion Date :	January 2015
Actual Study Completion Date :	January 2015

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma

MedlinePlus related topics: Melanoma

Drug Information available for: Cyclophosphamide Fludarabine Fludarabine phosphate

Genetic and Rare Diseases Information Center resources: Neuroendocrine Tumor Neuroepithelioma

U.S. FDA Resources

Arms and Interventions

Intervention Details:

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.

Outcome Measures

Primary Outcome Measures :

toxicity [ Time Frame: week 0 to 20 ]

Secondary Outcome Measures :

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

Eligibility Criteria

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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:

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.

Contacts and Locations

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): NCT00937625

Locations

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Denmark
Department of Oncology, Copenhagen University Hospital, Herlev
Herlev, Denmark, 2730

Sponsors and Collaborators

Inge Marie Svane

Investigators

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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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kristensen NP, Heeke C, Tvingsholm SA, Borch A, Draghi A, Crowther MD, Carri I, Munk KK, Holm JS, Bjerregaard AM, Bentzen AK, Marquard AM, Szallasi Z, McGranahan N, Andersen R, Nielsen M, Jönsson GB, Donia M, Svane IM, Hadrup SR. Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma. J Clin Invest. 2022 Jan 18;132(2). pii: e150535. doi: 10.1172/JCI150535.

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.

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Responsible Party:	Inge Marie Svane, Professor, Herlev Hospital
ClinicalTrials.gov Identifier:	NCT00937625
Other Study ID Numbers:	MM0909
First Posted:	July 13, 2009 Key Record Dates
Last Update Posted:	August 18, 2015
Last Verified:	August 2015

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 Vidarabine 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 Peripheral Nervous System Agents

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