Clinical trial NCT01946373: T Cell Transfer With or Without Dendritic Cell Vaccination in Patients With Melanoma
Official title: A Phase I Study to Evaluate Safety, Feasibility and Immunologic Response of Adoptive T Cell Transfer With or Without Dendritic Cell Vaccination in Patients With Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Melanoma
Keywords: Melanoma
Dendritic cell vaccination
Lymphodepletion
Adoptive cell transfer
T cells
Tumor infiltrating lymphocytes
Fludarabine
IL-2
Interleukin-2
Cyclophosphamide
Phase I study
Monocytes
Autologous
NY-ESO-1
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
First posted: 2013-09-19
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to learn if dendritic cell vaccine will increase the effect of tumor infiltrating lymphocytes given with chemotherapy and interleukin-2 in patients with melanoma.

Detailed description: The MAT02 clinical trial is a phase 1 clinical trial with the objective to assess the safety, feasibility and immunological efficacy of the combined application of two immunological treatment modalities in patients with metastatic melanoma:

1. Cohort A: After a non-myeloablative conditioning regimen, 5 patients will receive one bulk infusion of T cells. T cells will be expanded ex vivo from autologous tumor infiltrating lymphocytes (TIL). In vivo persistence of the infused cells will be supported by administration of IL-2, a T cell survival factor.
2. Cohort B: This adoptive cell transfer (ACT) step will in additional 10 patients be followed by a vaccination with autologous, in vitro-generated, dendritic cells (DC), loaded with autologous tumor lysate and a synthetically produced peptide derived from the tumor associated antigen NY-ESO 1.

Eligibility criteria: Inclusion Criteria:

* Patients with measurable (direct on body surface or by x-ray and/or CT) malignant melanoma (including uveal melanoma), that is advanced, inoperable stage III (advanced regional lymph node metastases, or more than 5 in-transit metastases, N2) or stage IV (distant metastasis, M1) according to the AJCC classification and confirmed by histology/cytology and appropriate radiological investigations.
* Patients with a palpable resectable lesion located in the skin or in a lymph node or a lesion accessible by (core) biopsy.
* Disease should be in progression and the patient should have exhausted other approved therapeutic options, if not the physician considers that an earlier study entry benefits the patient.
* Ambulatory performance status (ECOG 0, 1, 2).
* Age 18-74 and life expectancy greater than 3 months.

Exclusion Criteria:

* Any of the above criteria are not met.
* Significant history or current evidence of cardiovascular disease (e.g. uncontrolled congestive heart failure or hypertension, unstable coronary artery disease or serious arrhythmias) or major respiratory diseases. In questionable cases, a stress test should be performed.
* Recipients of a major organ allograft. Autoimmune diseases such as, but not limited to, inflammatory bowel disease or multiple sclerosis. Vitiligo is not an exclusion criterion. Other serious chronic diseases.
* Other serious illnesses, e.g. active infections requiring antibiotics, bleeding disorders.
* Has had prior systemic cancer therapy within the past four weeks at the time of the start of the lymphodepletion regimen.
* Patients diagnosed with prior malignancies (except adequately treated basal cell carcinomas of the skin or in situ carcinomas of the skin or in situ carcinomas of the cervix, surgically cured) within the past 5 years.
* Patients with second advanced malignancies concurrently.
* Active CNS metastases. (Note: Patients with brain metastases that have been completely resected at least one month prior to registration or have undergone gamma knife treatment with no evidence of recurrence on CT and who are neurologically stable, are not excluded).
* Organic brain syndrome or significant psychiatric disorder which would preclude participation in the full protocol and follow-up.
* Immunodeficiency, previous splenectomy or radiation therapy of the spleen.
* Screening laboratory values:

  a) Inadequate hematologic function defined by: i) White blood count (WBC) \<3.0 x 109/l ii) Platelet count \<100x109/l iii) Hemoglobin level \<100 g/l b) Inadequate hepatic function as defined by either: i) Total bilirubin level \>1.5 times the upper limit of normal (ULN) ii) Aspartate amino transferase (AST) or alanine amino transferase (ALT) \>3 times the ULN (if related to liver metastases \>5 times the ULN) c) Inadequate renal function defined as serum creatinine \>1.5 times the ULN
* Infectious diseases that can be transmitted via contact with blood, such as HIV, Hepatitis B and C.
* Women who are pregnant or nursing will be excluded because of the potentially dangerous effects of the preparative chemotherapy on the fetus.

Primary outcomes:
measure: Safety of the T cell therapy, with and without dendritic cell vaccine, as evaluated according to the NCI CTCAE scale version 4.0
timeFrame: 30 days
Secondary outcomes:
measure: Time to disease progression assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
Study officials:
affiliation: Karolinska University Hospital
name: Maria Wolodarski, MD
role: PRINCIPAL_INVESTIGATOR
References: