Neoplasms

All Conditions

Rare Diseases

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Immunomodulating Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Leukapheresis before start of radiotherapy. Immunization with DCs starting first week after finalizing radiotherapy (2Gy x 30) and concomitant temozolomide.

Radiotherapy (2 Gy x30) with concomitant and adjuvant temozolomide.

Dendritic cell immunization

After a 4-week break, patients were then to receive up to six cycles of adjuvant temozolomide according to the standard 5-day schedule every 28 days at 150 mg per square meter for the first cycle and thereafter increase to 200 mg per square meter beginning with the second cycle.

Adjuvant temozolomide

Einar O Vik-Mo, MD, PhD

Soveig Bringsli

Solveig Bringsli

Iver A Langmoen, MD, PhD

Open, randomized study of a trivalent dendritic cell therapy compared to standard therapy in primary treated patients with IDH wild-type, MGMT-promotor methylated glioblastoma. The IMP is dendritic cells transfected with mRNA of survivin, hTERT og autologous tumor stem cells derived from tumorspheres.

Autologous leukapheresis for enrichment of PBMCs is performed after enrollment of the patient into the trial. Ex vivo generated DCs will be frozen and stored in the vapour phase of liquid nitrogen.

At first surgery, tumor biopsies will be cultured under sphere-forming conditions under ex vivo conditions for enrichment of glioblastoma stem cells. mRNA will purified and amplified from these autologous tumor stem cells.

At specified intervals patients randomized to the vaccine group will receive intradermal injections of DCs transfected with mRNA from autologous tumor stem cells, survivin and hTERT. Injections will be given as three separate injections at three separate sites.

Vaccination will be continued for as long as there are vaccines available.

Dendritic Cell Immunotherapy Against Cancer Stem Cells in Glioblastoma Patients Receiving Standard Therapy

Open Label Randomized Phase II/III Trial of Dendritic Cell Immunotherapy Against Cancer Stem Cells in Glioblastoma Patients Receiving Standard Therapy (DEN-STEM)

Defined as time from first surgery to first certain progress of contrast enhancing tumor or clinical progression, according to the Response Assessment in Neuro-Oncology (RANO) criteria.

Evaluated by EORTC Quality of Life Questionaire (QLQ-C30), a questionnaire developed to assess the quality of life of cancer patients. Scale 30 to 120 points, where higher is worse.

Evaluated by EORTC Quality of Life Questionaire, Brain module (QLQ-BN20). The brain cancer module is meant for use among brain cancer patients varying in disease stage and treatment modality. Scale 20 to 80 points, where higher is worse. It should always be complemented by the QLQ-C30.

Evaluated by delayed type hypersensitivity reaction in skin.

Classified according to Common Terminology Criteria for Adverse Events (CTCAE).

Oslo University Hospital

Senior consultant

Skin and Connective Tissue Diseases

Melanoma

Neuroendocrine Tumors

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Antirheumatic Agents

Anti-Infective Agents

Analgesics

Vaccines

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Aldesleukin

Interleukin-2

Mesna

Immunosuppressive Agents

Immunologic Factors

Antimetabolites

Analgesics, Non-Narcotic

Protective Agents

Cyclophosphamide 60 mg/kg/d by vein (IV) over 2 hours Days -7 and -6 (with Mesna) and Fludarabine 25 mg/m\^2 IV daily Days -5 to -1 before T cell infusion. On Day 0, up to 1.5 x 10\^11 T cells IV infusion over 30-60 minutes. Interleukin-2 12-16 hours after T cell infusion at standard dose of 720,000 IU/kg as intravenous bolus over 15 minute period every 8-16 hours for up to 15 doses on Days 1-5 and 22-26.

Group A has been closed to new patient entry as of January 14, 2016.

Chemotherapy and IL-2 plus T-cells and the vaccine of dendritic cells received by vein (IV) about 4 hours after T-cells and again on Day 21 (+/- 7 days). Cyclophosphamide 60 mg/kg/d IV over 2 hours Days -7 and -6 (with Mesna) and Fludarabine 25 mg/m\^2 IV daily Days -5 to -1 before T cell infusion. On Day 0, up to 1.5 x 10\^11 T cells IV infusion over 30-60 minutes. Interleukin-2 12-16 hours after T cell infusion at standard dose of 720,000 IU/kg as intravenous bolus over 15 minute period every 8-16 hours for up to 15 doses on Days 1-5 and 22-26.

T-cells: 5.0x109 TIL administered on Day 1 and 10x109 TIL on Day 15.

IL-2: 1.2 MIU of IL- 2 on Days 2, 4, 9, 11, 16 and 18 as tolerated. After this period, patient receives twice weekly IL-2 that will be gradually changed to weekly IL-2. After 4-6 weeks, patients switched to IL-2.

1x10\^7 to 2.5x10\^8 MART-1 peptide-pulsed Dendritic Cells given by vein over 20-30 minutes approximately 4 hrs after receiving T cells.

Dendritic Cell Immunization

60 mg/kg/d by vein over 2 hours on Days -7 and -6 before T cell infusion

25 mg/m\^2 by vein daily over 30 minutes on Days -5 to -1 before T cell infusion.

On Days 0, up to 1.5 x 10\^11 T-cells by vein infusion over 30-60 minutes.

T-Cells

12-16 hours after completing the T cell infusion, all will receive high dose IL-2 on an inpatient basis at the standard dose of 720,000 IU/kg as an intravenous bolus over approximately a 15 minute period every 8-16 hours for up to 15 doses on Days 1-5 and 22-26 (+/- 7 days), as tolerated.

60 mg/kg with D5W or NS at 125 ml/hr infused intravenously over 24 hours on Day -7 and -6.

5.0x10\^9 T-cells administered on Day 1, and 10x10\^9 T-cells on Day 15. 1.2 MIU of IL- 2 on Day 2, 4, 9, 11, 16 and 18 as tolerated.

Intrathecal T-Cells

1.2 MIU of IL- 2 on Day 2, 4, 9, 11, 16 and 18 as tolerated. Then, patient receives twice weekly IL-2 that will be gradually changed to weekly IL-2. After 4-6 weeks patients switched to IL-2 maintenance.

Intrathecal Interleukin-2

Rodabe N. Amaria, MD

Objectives:

The primary objective will be to determine whether patients receiving the combination of dendritic cells and high dose IL-2 (Cohort A) have sustained persistence of infused T cells compared to patients treated with T cells and high dose IL-2 alone.

Secondary endpoints will include evaluations for tumor response and studies to determine whether dendritic cells enhance the infused T cells in anti-tumor activity and their ability to migrate to the tumor site. In addition, we will evaluate the characteristics of the infused T cells that correspond with effectiveness in vivo.

Additionally, secondary objectives will include correlation of clinical parameters with survival (overall survival and progression-free survival) for all cohorts.

COHORT C

In a separate cohort (Cohort C) the primary endpoint will be the overall response rate of TIL treatment for patients who have not achieved PR or CR or have progressive disease from treatment of the BRAF inhibitor alone.

COHORT D

The primary objective of Cohort D is to confirm the safety of adoptively transferred, TIL into the CSF.

The secondary objective is the evaluation of clinical imaging and CSF response. Correlative objectives will assess if the intrathecally-infused T cells persist in the CSF, assess circulating tumor cells in the CSF, and assess various cytokine and other analyses,as feasible.

COHORT E

The primary objective of Cohort E is to determine the overall response rate of TIL treatment with cells grown by the TIL 3.0 pre-REP (Turnstile 1) phase of cellular growth.

Lymphodepletion Plus Adoptive Cell Transfer With or Without Dendritic Cell Immunization in Patients With Metastatic Melanoma

Objective response (OR) defined as immune-related Best Overall Response (irBOR). irBOR is best confirmed immune-related response criteria (irRC) overall response over the study as a whole, recorded between the date of first dose until the last tumor assessment before subsequent therapy (except for local palliative radiotherapy for painful bone lesions) for the individual subjects in the study.

Longitudinal immune response defined as: Conversion of positive to negative cytology. Any perceptible improvement of the MRI findings confirmed by radiologist and/or the investigator confirmed by 2 successive MRIs 4 weeks apart. Any clinical improvement in terms of neurological symptoms.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Dendritic Cell Immunotherapy Against Cancer Stem Cells in Glioblastoma Patients Receiving Standard Therapy	NCT03548571	Glioblastoma	Dendritic cell ... Adjuvant temozo...	18 Years - 70 Years	Oslo University Hospital
Lymphodepletion Plus Adoptive Cell Transfer With or Without Dendritic Cell Immunization in Patients With Metastatic Melanoma	NCT00338377	Melanoma	Dendritic Cell ... Cyclophosphamid... Fludarabine T-Cells Interleukin-2 Mesna Intrathecal T-C... Intrathecal Int...	12 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for dendritic cell immunization