Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Nervous System Diseases

Rare Diseases

Sarcoma

Liposarcoma

Histiocytoma, Malignant Fibrous

Testicular Neoplasms

Chondrosarcoma

Fibrosarcoma

Histiocytoma

Leiomyosarcoma

Rhabdomyosarcoma

Sarcoma, Synovial

Neurofibrosarcoma

Sarcoma, Alveolar Soft Part

Neoplasms, Connective and Soft Tissue

Myosarcoma

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Synovial Sarcoma

Malignant Peripheral Nerve Sheath Tumor

All Drugs and Chemicals

Vaccines

Immunomodulating Agents

Immunologic Factors

Autologous dendritic cell vaccine loaded with allogeneic tumor lysate expression of cancer testis antigens

Autologous dendritic cell vaccine

Yuriy Komarov, PhD

The purpose of this study is to achieving a six-month progression free survival (PFS) of patients receiving autologous dendritic cell vaccine (ADKV) loaded with allogeneic tumor lysate expression of cancer-testis antigens (CTA) in patients with soft tissue sarcomas

Vaccination is carried out on the planned days ± 3 days

1. All examinations must be performed before the vaccine is administered.

   * Full physical examination.
   * Assessment of vital signs (blood pressure, temperature, heart rate), the general condition of the patient and physical activity.
   * Evaluation of concomitant therapy.
   * Assessment of vital signs.
   * Laboratory safety and immunological indicators
   * Assessment of adverse events, symptoms and syndromes of the disease.
2. Introduction of CV in accordance with the dose determined for a given vaccination (see section 9.2. - procedures for delivery and use)
3. After administration, patients are observed for at least 1 hour. An assessment of vital indicators. Undesirable effects detected at the introduction are recorded.

Autologous Dendritic Cell Vaccine in Patients With Soft Tissue Sarcoma

Non-randomized Single-center Study Phase II Evaluating the Efficacy and Toxicity of Autologous Dendritic Cell Vaccine Loaded With Allogeneic Tumor Lysate Expression of Cancer Testis Antigens in Patients With Soft Tissue Sarcoma

Achieving a six-month time to progression (PFS) 40% of patients receiving ADKV loaded with allogeneic tumor lysate expressing PTA in patients with soft tissue sarcomas

The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse. In a clinical trial, measuring the progression-free survival is one way to see how well a new treatment works

The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that half of the patients in a group of patients diagnosed with the disease are still alive. In a clinical trial, measuring the median overall survival is one way to see how well a new treatment works

The percentage of patients whose cancer shrinks or disappears after treatment.

Сhanging level of T lymphocytes subpopulation in peripheral blood

N.N. Petrov National Medical Research Center of Oncology

Skin and Connective Tissue Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

HLA-A2.1 patients are vaccinated with dendritic cells loaded with MHC Class I restricted epitopes of tumor antigens gp100 and tyrosinase

HLA-A2.1 and HLA-DR4 patients are vaccinated with dendritic cells loaded with MHC Class I and II restricted epitopes of tumor antigens gp100 and tyrosinase

HLA-A2.1 and/or HLA-DR4 patients are vaccinated with dendritic cells transfected with mRNA encoding tumor antigens gp100 and tyrosinase

autologous dendritic cell vaccine

Prof. C.J.A. Punt, MD, PhD

Prof. G.J. Adema, PhD

Dendritic cells (DCs)are the most potent antigen-presenting cells of the immune system, as such they are able to direct the immune system specifically against cancer cells. Currently DCs are used in clinical vaccination studies and immunological and clinical responses have been observed. For inducing anti-tumor immunity, the DCs have to be loaded with tumor antigen (i.e. molecular structures that are presented by the tumor, that are recognized by the immune system). Currently most studies use tumor peptides (small protein fragments) for this purpose. This approach has several disadvantages: only patients with a certain HLA-type can be treated and the immune response that is induced by the vaccine is limited to the used peptides. These disadvantages do not exist when the DCs present antigen which is endogenously processed, for example after RNA transfection. For this reason we investigate the immunogenicity of DCs that are pulsed with peptides or transfected with mRNA encoding melanoma associated antigens in stage III and IV melanoma patients.

Peptide-pulsed vs. RNA-transfected Dendritic Cell Vaccines in Melanoma Patients

In Vivo Responses of DC Vaccines Presenting HLA Class I and II Restricted Tumor Epitopes Either by Peptide-pulsing or mRNA Transfection in Melanoma Patients

Dutch Cancer Society

Radboud University Medical Center

Antineoplastic Agents

Analgesics

Interleukin-2

Daily 3 MU Interleukin 2 will be administered subcutaneously for 5 days starting from the second day after each vaccine dose. Vaccine doses will be given intradermally in two sites close to inguinal or axillary lymphnode stations that had not site of previous surgical exeresis.The first dose (WK1) will consist of freshly prepared vaccine, whereas for all the further doses cryopreserved aliquots will be utilized. The remaining 5 doses will be administered every 4 weeks to complete six months of therapy (six vaccines).

Arm B: Patients will undergo laboratory and clinical assessment, tumor re-staging, blood collection for immunological biomarkers every 12 weeks until relapse.

The Dendritic Cells vaccine is given intradermally with 5 injections in sites close to inguinal or axillary lymphnode stations that had not site of previous surgical exeresis; as a rule, vaccine administrations should be performed by alternating injections sites. Two days after each vaccine administration, daily 3 MU Interleukin 2 will be administered subcutaneously for 5 days.

Autologous Dendritic Cell vaccine

Laura Ridolfi, MD

This phase II, randomized, open-label trial aims to assess whether the vaccination increase RFS in disease free melanoma patients after surgery. Patients will be randomized between Intradermal Autologous Dendritic Cell Vaccine loaded with autologous tumor lysate or homogenate (6 vaccines every 4 weeks) and observation.

This study will be a randomized phase II trial (1:1 allocation ratio) in resected stage III/IV melanoma patients. The randomization list will be stratified by stage (III and IV M1a-b and IVM1c), and time from primitive tumor to first metastasis (≤ 2 years versus \> 2 years). Five randomization lists will be defined, one for each stratum.

On the basis of literature, the investigators assume a median relapse-free survival of 7.0 months for the standard group. With a two-sided tailed alpha of 0.10 and power of 80%, assuming a median relapse-free survival of 11.7 months in the experimental arm (hazard ratio 0.60), it will be necessary to recruit 60 patients per arm over a period of 24 months and to have a subsequent 12 months of follow-up. In the context of data monitoring board activities, an interim analysis for futility, according to the Bayesian approach, will be performed at 18 months in order to control the safety.

Primary endpoints will be relapse free survival. Secondary end points will be OS, In vivo and in vitro immunomonitoring. Immunologic efficacy will be measured by best Delayed Type Hypersensitivity score (reactivity to lysate or KLH) obtained after at least 4 vaccine doses, alone or combined with Interferon-g ELISPOT analysis of tumor antigen-specific circulating effectors obtained after a minimum of 4 vaccine doses, both compared with prevaccine samples. In vivo monitoring will focus on functional phenotyping of circulating immune effectors/regulators, functional characterization of circulating tumor antigen-specific immune effectors and regulators, and identification of serum markers that are predictive of response.

Complementary Vaccination With Dendritic Cells Pulsed With Autologous Tumor Lysate in Resected Stage III and IV Melanoma Patients.

Complementary Vaccination With Dendritic Cells Pulsed With Autologous Tumor Lysate in Resected Stage III and IV Melanoma Patients: a Phase II Randomized Trial (ACDC Adjuvant Trial)

Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Symptoms and General Pathology

Infections

Blood and Lymph Conditions

Immune System Diseases

Syndrome

Mycoses

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Mycosis Fungoides

Lymphoma, T-Cell, Cutaneous

Sezary Syndrome

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Peripheral T-cell Lymphoma

Cutaneous T-cell Lymphoma

Autologous Dendritic Cell Vaccine

Larisa J. Geskin, M.D.

This research is being done to look at the safety and value of a vaccine for a cancer found in the blood and skin known as Cutaneous T-cell lymphoma (CTCL) and Sezary Syndrome.

In the laboratory, researches found that special white blood cells, called dendritic cells (DCs), are able to stimulate the immune system (groups of cells that protect the body from germs and diseases) in a way that helps your body fight cancer. Autologous (from your own body) DCs will be prepared (mixed together) in the laboratory with your cancer cell (Sezary cells) to allow your DCs to pick up parts of your Sezary cells to make the vaccine for you.

Although the etiology of CTCL is not completely understood, immunologic factors appear to play an important role.

Dendritic Cell (DC)-tumor cell vaccines have several features that suggest applications for the immunotherapy of human tumors. Importantly, DC-tumor cell immunization has the potential to simultaneously stimulate CD4+ and CD8+ T cell-mediated immunity against multiple tumor antigens.

The vaccine will be prepared from the subject's own blood, obtained during leukapheresis. From leukapheresed blood, monocyte-derived DCs and malignant lymphocytes will be isolated. The DCs will then be loaded with lymphocyte-derived tumor antigens. Formulations and release criteria must be met before vaccine can be administered.

Completion date provided represents the completion date of the grant per OOPD records

Immunization Against Tumor Cells in Sezary Syndrome

Phase II Evaluation of Immunization Against Tumor Cells in Subjects With Sezary Syndrome Using Autologous Mature Dendritic Cells

University of Pittsburgh

vaccination with autologous dendritic cells treated with mRNA electroporation for single-step antigen loading and TLR activation (TriMix-DC)

vaccination with autologous dendritic cells treated with mRNA electroporation for antigen loading and separately for TLR activation

Autologous monocyte-derived dendritic cells electroporated with mRNA encoding gp100 and tyrosinase (for antigen loading), active TLR4 and CD70 (for activation). Dendritic cells are vaccinated intranodally 3 times with biweekly intervals every 6 months, if no signs of progression, for a total of 9 vaccinations

Autologous monocyte-derived dendritic cells electroporated with mRNA encoding gp100 and tyrosinase and matured with either cytokines or TLR ligands. Dendritic cells are vaccinated intranodally 3 times with biweekly intervals every 6 months, if no signs of progression, for a total of 9 vaccinations

C.J.A. Punt, prof.dr.

Objectives: This is an exploratory study, consisting of two parts. In part I dose escalation is performed and the primary objective is the safety of different doses of TLR-DC and Trimix DC. In part II Trimix DC vaccination will be compared with TLR-DC vaccination and the primary objective of this part is the immunological response, with toxicity and clinical efficacy being secondary objectives. These studies will provide important data on the safety and immunological effects of TLR-DC and Trimix DC.

Study design: Part I of this study is an open label dose escalation study. Part II of this study is an open label randomized phase II study.

Study population: Our study population consists of melanoma patients, with proven expression of melanoma associated tumor antigens gp100 and tyrosinase. Melanoma patients with regional lymph node metastasis in whom a radical lymph node dissection is performed within 2 months of inclusion in this study (further referred to as stage III) and melanoma patients with measurable distant metastases (further referred to as stage IV) will be included.

1. Rationale Immunotherapy applying ex vivo generated and tumor-antigen-loaded dendritic cells (DC) has now successfully been introduced in the clinic. A limited, but consistent, number of objective immunological and clinical responses have been observed. Thusfar it remains unclear why some patients respond and others not, but there is a general consensus that the current protocols applied to generate DC may not result in the induction of optimal Th1 responses. The investigators and others have demonstrated that DC maturation is one of the crucial factors, not only for effective DC migration but also to induce effective anti-tumor immune responses in cancer patients. Currently, the "golden standard" used to mature DC consists of a cocktail of pro-inflammatory cytokines (IL-1b, IL-6, TNFa) and prostaglandin E2 (PGE2). Recent mouse data demonstrated, however, that maturation of DC by solely pro-inflammatory cytokines yielded DC that supported T cell clonal expansion, but failed to efficiently direct effector T cell differentiation. Interestingly, DC matured in the presence of Toll like receptor (TLR) ligands were able to induce full T cell effector function and unleashed more potent immune responses. The investigators recently identified vaccines against infectious diseases that contain TLR ligands and are capable of inducing DC maturation. This knowledge provides a new application for these clinical applicable agents: clinical grade DC stimulators. A clinical grade DC maturation protocol is developed in which TLR ligands (preventive vaccines) and PGE2 are combined which resulted in the generation of mature DC that secrete high levels of the key cytokine IL-12. Moreover, these TLR-ligand matured DC (TLR-DC) induced T cells secreting at least 20-fold higher levels of the effector cytokines IFNa and TNFa as compared to DC matured in the absence of TLR ligands.

   In the group of Kris Thielemans and it was shown that the T-cell stimulatory capacity of peptide-pulsed DC can be greatly enhanced by providing them with three different molecular adjuvants through electroporation with mRNA encoding a so-called TriMix of CD40 ligand (CD40L), CD70, and a constitutively active form of TLR4 (caTLR4). The combination of CD40L and caTLR4 electroporation would mimic CD40 ligation and TLR4 signaling of the DC and generates phenotypically mature, cytokine/chemokine-secreting DC, as has been shown for CD40 and TLR4 ligation through addition of soluble CD40L and lipopolysaccharide. On the other hand, the introduction of CD70 into the DC would provide a costimulatory signal to CD27+ naive T cells by inhibiting activated T cell apoptosis and by supporting T cell proliferation.

   In conclusion, these in vitro data demonstrate that both TLR-DC and Trimix DC are promising candidates to improve immunological and clinical responses in cancer immunotherapy.
2. Objectives This is an exploratory study, consisting of two parts. In part I dose escalation is performed and the primary objective is the safety of different doses of TLR-DC and Trimix DC. In part II Trimix DC vaccination will be compared with TLR-DC vaccination and the primary objective of this part is the immunological response, with toxicity and clinical efficacy being secondary objectives. These studies will provide important data on the safety and immunological effects of TLR-DC and Trimix DC.
3. Study design Part I of this study is an open label dose escalation study. Part II of this study is an open label randomized phase II study.
4. Study population Our study population consists of melanoma patients, with proven expression of melanoma associated tumor antigens gp100 and tyrosinase. Melanoma patients with regional lymph node metastasis in whom a radical lymph node dissection is performed within 2 months of inclusion in this study (further referred to as stage III) and melanoma patients with measurable distant metastases (further referred to as stage IV) will be included.
5. Main study endpoints The primary objectives of the study are to investigate the toxicity of TLR-DC and Trimix DC by dose escalation of DC numbers in part I, and to investigate immunological responses upon DC vaccination in part II of the study.

Immunological responses are:

1. The activation of immune cells in vivo.
2. The immunological response induced with TLR-DC and Trimix DC loaded with mRNA encoding melanoma-associated tumor antigens (gp100 and tyrosinase).

Safety and clinical efficacy are secondary objectives.

Single-step Antigen Loading and TLR Activation of Dendritic Cells in Melanoma Patients

Single-step Antigen Loading and TLR Activation of Dendritic Cells by mRNA Electroporation for Vaccination in Stage III and IV Melanoma Patients

The immunological response induced with TLR-DC and Trimix DC loaded with mRNA encoding melanoma-associated tumor antigens (gp100 and tyrosinase) will be evaluated by using 1. tetramer screening of skin-test biopsy derived cell-cultures and peripheral blood, 2. cytokine-bead assay to measure specific cytokine production of skin-test biopsy derived cell-cultures upon differential stimulation and 3. KLH-specific antibody and proliferative responses

toxicity will be reported with regard to 1. flu-like symptoms, 2. local injection site reaction and 3. other signs and symptoms, graded according to CTC version 3.0, numbers of patients and CTC grade will be reported

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Autologous Dendritic Cell Vaccine in Patients With Soft Tissue Sarcoma	NCT01883518	Sarcoma Neoplasms, Conn...	Autologous dend...	18 Years -	N.N. Petrov National Medical Research Center of Oncology
Peptide-pulsed vs. RNA-transfected Dendritic Cell Vaccines in Melanoma Patients	NCT00243529	Melanoma Stage ...	autologous dend...	18 Years - 75 Years	Radboud University Medical Center
Complementary Vaccination With Dendritic Cells Pulsed With Autologous Tumor Lysate in Resected Stage III and IV Melanoma Patients.	NCT02718391	Malignant Melan... Adjuvant Drug T... Vaccin Therapy	Autologous Dend...	18 Years -	Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Immunization Against Tumor Cells in Sezary Syndrome	NCT00099593	Cutaneous T-cel... Sezary Syndrome	Autologous Dend...	18 Years -	FDA Office of Orphan Products Development
Single-step Antigen Loading and TLR Activation of Dendritic Cells in Melanoma Patients	NCT01530698	Melanoma	autologous dend... autologous dend...	18 Years - 70 Years	Radboud University Medical Center
Peptide-pulsed vs. RNA-transfected Dendritic Cell Vaccines in Melanoma Patients	NCT00243529	Melanoma Stage ...	autologous dend...	18 Years - 75 Years	Radboud University Medical Center
Peptide-pulsed vs. RNA-transfected Dendritic Cell Vaccines in Melanoma Patients	NCT00243529	Melanoma Stage ...	autologous dend...	18 Years - 75 Years	Radboud University Medical Center
Single-step Antigen Loading and TLR Activation of Dendritic Cells in Melanoma Patients	NCT01530698	Melanoma	autologous dend... autologous dend...	18 Years - 70 Years	Radboud University Medical Center

Spots Global Cancer Trial Database for autologous dendritic cell vaccine