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

Primary Purpose

Melanoma

Status
Recruiting
Phase
Phase 1
Locations
Sweden
Study Type
Interventional
Intervention
Cyclophosphamide
Fludarabine
T cells
Interleukin-2
Dendritic cell vaccine
Sponsored by
Karolinska University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma focused on measuring 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

Eligibility Criteria

18 Years - 74 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Karolinska University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Chemotherapy + T cells + IL-2

Chemotherapy + T cells + IL-2 + DCV

Arm Description

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 over 15 minute period every 8-hours for up to 14 doses.

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 over 15 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.

Outcomes

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

Secondary Outcome Measures

Time to disease progression assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Full Information

First Posted
September 12, 2013
Last Updated
October 3, 2022
Sponsor
Karolinska University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01946373
Brief Title
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

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 2013 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Karolinska University Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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: 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. 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.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Chemotherapy + T cells + IL-2
Arm Type
Experimental
Arm Description
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 over 15 minute period every 8-hours for up to 14 doses.
Arm Title
Chemotherapy + T cells + IL-2 + DCV
Arm Type
Experimental
Arm Description
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 over 15 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.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Sendoxan, Cytoxan, Neosar
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludarabine phosphate, Fludara
Intervention Type
Biological
Intervention Name(s)
T cells
Intervention Type
Biological
Intervention Name(s)
Interleukin-2
Other Intervention Name(s)
IL-2, Proleukin
Intervention Type
Biological
Intervention Name(s)
Dendritic cell vaccine
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Time to disease progression assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Time Frame
4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maria Wolodarski, MD
Phone
+46851770000
Email
maria.wolodarski@regionstockholm.se
First Name & Middle Initial & Last Name or Official Title & Degree
Rolf Kiessling, MD, PhD
Phone
+46733428848
Email
rolf.kiessling@ki.se
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maria Wolodarski, MD
Organizational Affiliation
Karolinska University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Karolinska University Hospital
City
Stockholm
ZIP/Postal Code
SE-171 76
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria Wolodarski, MD
Phone
+46851770000
Email
maria.wolodarski@regionstockholm.se
First Name & Middle Initial & Last Name & Degree
Maria Wolodarski, MD

12. IPD Sharing Statement

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

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