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T Cell Transfer With or Without Dendritic Cell Vaccination in Patients With Melanoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Karolinska University Hospital
Sponsor:
Information provided by (Responsible Party):
Roger Tell, Karolinska University Hospital
ClinicalTrials.gov Identifier:
NCT01946373
First received: September 12, 2013
Last updated: September 8, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Melanoma
Drug: Cyclophosphamide
Drug: Fludarabine
Biological: T cells
Biological: Interleukin-2
Biological: Dendritic cell vaccine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Karolinska University Hospital:

Primary Outcome Measures:
  • Safety of the T cell therapy, with and without dendritic cell vaccine, as evaluated according to the NCI CTCAE scale version 4.0 [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to disease progression assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: October 2013
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chemotherapy + T cells + IL-2
Cyclophosphamide 60 mg/kg/d by vein (IV) daily for 2 days followed by fludarabine 25 mg/m^2 IV daily for 5 days before T cell infusion. The day after chemotherapy up to 5 x 10^10 T cells IV infusion. Interleukin-2 90 minutes after T cell infusion at a dose of 100,000 IU/kg as IV bolus over15 minute period every 8-hours for up to 14 doses.
Drug: Cyclophosphamide
Other Names:
  • Sendoxan
  • Cytoxan
  • Neosar
Drug: Fludarabine
Other Names:
  • Fludarabine phosphate
  • Fludara
Biological: T cells Biological: Interleukin-2
Other Names:
  • IL-2
  • Proleukin
Experimental: Chemotherapy + T cells + IL-2 + DCV
Cyclophosphamide 60 mg/kg/d by vein (IV) daily for 2 days followed by fludarabine 25 mg/m^2 IV daily for 5 days before T cell infusion. The day after chemotherapy up to 5 x 10^10 T cells IV infusion. Interleukin-2 90 minutes after T cell infusion at a dose of 100,000 IU/kg as IV bolus over15 minute period every 8-hours for up to 14 doses. After completion of the IL-2 treatment 3-5 doses of weekly intradermal vaccinations with up to 1.5 x 10^7 Dendritic cells pulsed with autologous tumor lysate and NY-ESO-1 peptide.
Drug: Cyclophosphamide
Other Names:
  • Sendoxan
  • Cytoxan
  • Neosar
Drug: Fludarabine
Other Names:
  • Fludarabine phosphate
  • Fludara
Biological: T cells Biological: Interleukin-2
Other Names:
  • IL-2
  • Proleukin
Biological: Dendritic cell vaccine

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 5 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

Ages Eligible for Study:   18 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with measurable (direct on body surface or by x-ray and/or CT) malignant 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. The lesion should be confirmed to be melanoma by fine needle biopsy.
  • Disease should be in progression and the patient should have exhausted other approved therapeutic options.
  • Ambulatory performance status (ECOG 0, 1, 2).
  • Age 18-74 and life expectancy greater than 3 months.
  • Patients must have been evaluated with imaging studies (MRI/CT/US/PET-CT) to establish metastasis/advanced disease in the period of 30 days prior to the initiation of the trial.

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).
  • Patients with second advanced malignancies concurrently.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01946373

Contacts
Contact: Roger Tell, MD, PhD +46760293911 roger.tell@karolinska.se
Contact: Rolf Kiessling, MD, PhD +46733428848 rolf.kiessling@ki.se

Locations
Sweden
Karolinska University Hospital Recruiting
Stockholm, Sweden, SE-171 76
Contact: Roger Tell, MD, PhD    +46760293911    roger.tell@karolinska.se   
Principal Investigator: Roger Tell, MD, PhD         
Sponsors and Collaborators
Karolinska University Hospital
Investigators
Principal Investigator: Roger Tell, MD, PhD Karolinska University Hospital
  More Information

No publications provided

Responsible Party: Roger Tell, Dr, Karolinska University Hospital
ClinicalTrials.gov Identifier: NCT01946373     History of Changes
Other Study ID Numbers: MAT-02, 2012-000450-63
Study First Received: September 12, 2013
Last Updated: September 8, 2014
Health Authority: Sweden: Medical Products Agency

Keywords provided by Karolinska University Hospital:
Melanoma
IL-2
Interleukin-2
Dendritic cell vaccination
Lymphodepletion
Adoptive cell transfer
T cells
Tumor infiltrating lymphocytes
Fludarabine
Cyclophosphamide
Phase I study
Monocytes
Autologous
NY-ESO-1

Additional relevant MeSH terms:
Melanoma
Nevi and Melanomas
Interleukin-2
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Alkylating Agents
Analgesics
Analgesics, Non-Narcotic
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Central Nervous System Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014