Neoplasms

Symptoms and General Pathology

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Neoplasm Metastasis

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Arm-A, patients will receive Dendritic Cell therapy during one year following randomization.

Arm-B, patients will initiate Dendritic Cell therapy only after documented recurrence of the melanoma that cannot be salvaged by local therapy.

Dendritic cell therapy

Bart Neyns, Phd Md

This is an open label, 2-arm, 1-stage, randomized controlled phase II study in patients with AJCC stage IIIB/C \& -IV melanoma. At baseline tumor assessment (using total body FDG-PET/CT), patients should be free from measurable tumor lesions (according to RECISTv1.1 definitions) following prior local therapy (e.g. following surgical resection, isolated limb perfusion, radiofrequency ablation, cryotherapy, radiotherapy, electrochemotherapy, ...). Patients should not have symptomatic non-measurable tumor lesions (e.g. bone metastasis, or pleural effusion), and lesions treated by prior local therapy should be free from progression. Patients should not have received any prior systemic therapy (non-experimental or experimental).

This is an open label, 2-arm, 1-stage, randomized controlled phase II study in patients with AJCC stage IIIB/C \& -IV melanoma. At baseline tumor assessment (using total body FDG-PET/CT), patients should be free from measurable tumor lesions (according to RECISTv1.1 definitions) following prior local therapy (e.g. following surgical resection, isolated limb perfusion, radiofrequency ablation, cryotherapy, radiotherapy, electrochemotherapy, ...). Patients should not have symptomatic non-measurable tumor lesions (e.g. bone metastasis, or pleural effusion), and lesions treated by prior local therapy should be free from progression. Patients should not have received any prior systemic therapy (non-experimental or experimental).

* Patients will be randomized between two treatment arms (Arm-A and -B). In study Arm-A, patients will receive DC-administrations during one year following randomization. Salvage treatment by local therapies will be allowed during the study treatment in Arm-A. In study Arm-B, patients will initiate DC-administrations only after documented recurrence of the melanoma that cannot be salvaged by local therapy.
* The primary endpoint of this clinical trial is to determine the rate (%) of patients who are free from macrometastases (: measurable tumor lesions and symptomatic non-measurable tumor lesions) at 1-year (= 52 weeks) after randomization.

Patients treated on Arm-B will serve as a contemporary control-arm to help interpreting the outcome of patients treated in Arm-A. By design (phase II) this trial will not be powered to statistically prove a predefined difference between the two study arms (this would require a phase III design). Patients treated in Arm-B will be able to initiate immunotherapy with autologous DC at the time of recurrence that can not be salvaged by local therapy. Documentation of the anti-tumor activity and survival following DC-treatment at recurrence in Arm-B patients will be a secondary objective of this clinical trial.

mRNA Electroporated Autologous Dendritic Cells for Stage III/IV Melanoma

Randomized Controlled Phase II Clinical Trial on mRNA Electroporated Autologous Dendritic Cells for Stage III/IV Melanoma Patients Who Are Disease-free Following the Local Treatment of Macrometastases.

Patients will be evaluated 52 weeks following randomization for their melanoma disease status (= macro-metastases present or absent)

Patients will be followed continuous during their study participation for adverse events

RIZIV

Universitair Ziekenhuis Brussel

Head of devision (Medical Oncology)

Blood and Lymph Conditions

Immune System Diseases

Behaviors and Mental Disorders

Recurrence

Lymphoma

Lymphoma, T-Cell

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Aggression

Lymphoma, Non-Hodgkin

Leukemia

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Disease Attributes

Leukemia, B-Cell

Leukemia, Lymphoid

Hematologic Diseases

Chronic Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Mantle Cell Lymphoma

Follicular Lymphoma

B-cell Lymphoma

Marginal Zone Lymphoma

Diffuse Large B-Cell Lymphoma

Chronic Graft Versus Host Disease

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Pembrolizumab

Vaccines

Immunoglobulins

Heptavalent Pneumococcal Conjugate Vaccine

Immunologic Factors

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive pembrolizumab IV on day 1. Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive dendritic cell therapy IT on days 2, 8, and 15 of cycles 2 and 3, and day 2 of cycles 4 and 5. Patients undergo cryosurgery on day 2 of cycle 2 and receive pneumococcal 13-valent conjugate vaccine by injection on day 2 of cycles 2-5. Treatment repeats every 21 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. Patients who are CR, PR, or SD after completion of therapy, may receive pembrolizumab for an additional 18 cycles in the absence of disease progression or unacceptable toxicity.

Cryosurgery

Dendritic Cell Therapy

Laboratory Biomarker Analysis

Pneumococcal 13-valent Conjugate Vaccine

Quality-of-Life Assessment

Yi Lin

This phase I/II trial studies the best dose and side effects of dendritic cell therapy, cryosurgery and pembrolizumab in treating patients with non-Hodgkin lymphoma. Vaccines, such as dendritic cell therapy made from a person's tumor cells and white blood cells may help the body build an effective immune response to kill tumor cells. Cryosurgery kills cancer cells by freezing them. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving dendritic cell therapy, cryosurgery and pembrolizumab may work better at treating non-Hodgkin lymphoma.

PRIMARY OBJECTIVES:

I. Evaluate the optimal dose schedule, safety and tolerability as measured by the incidence of significant toxicity of combination therapy with anti-PD-1 monoclonal antibody, cryoablation, and intra-tumor injection of autologous dendritic cell into the cryoablated tumor. (Phase I) II. Test the efficacy (overall response rate) of combination therapy with anti-PD-1 monoclonal antibody, cryoablation, and intra-tumor injection of autologous dendritic cell vaccine. (Phase II)

SECONDARY OBJECTIVES:

I. Evaluate the feasibility of this combination immunotherapy. (Phase I) II. Evaluate patient quality of life. (Phase I) III. Evaluate the partial response (PR) and complete response (CR) rate of this combination immunotherapy. (Phase II) IV. Evaluate the progression free survival, treatment free survival, duration of response, disease-free rate at 2 years, and overall survival of this combination immunotherapy. (Phase II) V. Evaluate the safety of this combination immunotherapy. (Phase II)

CORRELATIVE OBJECTIVES:

I. Assess the effect of combination immunotherapy on patients' immune status and anti-tumor immune response. (Phase II) II. Assess the potential association between PD-1/PD-L1/PD-L2 expression in tumor and blood with clinical efficacy. (Phase II) III. Assess the potential association between tumor antigen mutations and antigen-specific immune response with clinical efficacy. (Phase II) IV. Evaluate patient quality of life. (Phase II)

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive pembrolizumab intravenously (IV) on day 1. Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive dendritic cell therapy intratumorally (IT) on days 2, 8, and 15 of cycles 2 and 3, and day 2 of cycles 4 and 5. Patients undergo cryosurgery on day 2 of cycle 2 and receive pneumococcal 13-valent conjugate vaccine by injection on day 2 of cycles 2-5. Treatment repeats every 21 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. Patients who are CR, PR, or stable disease (SD) after completion of therapy, may receive pembrolizumab for an additional 18 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months during the first year post-treatment, every 4 months during the second year post-treatment, and then every 6 months for up to 2 years.

Dendritic Cell Therapy, Cryosurgery, and Pembrolizumab in Treating Patients With Non-Hodgkin Lymphoma

Phase I/II Study of Dendritic Cell Therapy Delivered Intratumorally After Cryoablation and Anti-PD-1 Antibody (Pembrolizumab) for Patients With Non-Hodgkin Lymphoma

Measurements of index lesion(s) (non-cryoablated lesion) will be evaluated over time for each patient as a marker of systemic immune and treatment response to pembrolizumab and localized treatment with cryoablation and dendritic cell therapy. The index lesion(s) will be selected by the treating physician/investigator and are noncryoablated node. The percent change from baseline in index lesion measurements will be assessed over time. Differences in values over time will be summarized descriptively and graphically. The whole body computed tomography (CT) or positron emission tomography/CT will be used to assess overall clinical response and time to progression using the standard Cheson criteria.

Will be evaluated and summarized both quantitatively and graphically. Each of the correlative endpoints will be summarized individually, but will also be evaluated in terms of their relationships to one another; i.e., will use Spearman rank correlation coefficient to assess the correlations between baseline levels as well as between changes before and after treatment in these immunologic markers. In addition, these immunologic markers will be correlated with cancer and treatment- related outcomes (e.g. response, toxicities). Relationships will also be explored graphically using scatter plots.

MTD will be defined as the dose level that does not induce dose limiting toxicity in at least one-third of patients.

The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated.

The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated. The response rate will be calculated, in each individual cohort as supplementary.

The distribution of survival time will be estimated using the method of Kaplan-Meier.

The distribution of treatment-free survival will be estimated using the method of Kaplan-Meier.

The distribution of duration of complete response will be estimated using the method of Kaplan-Meier.

Will be assessed by Common Terminology Criteria for Adverse Events version 4.0. The maximum grade for each type of adverse event at each evaluation will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Longitudinal analysis techniques will be utilized to determine the effect of time on treatment adverse events.

Will be measured using the Functional Assessment of Cancer Therapy-lymphoma. The assessment will be scored according to the scoring algorithm. Changes from baseline will be calculated at each assessment time points. Mean change scores at each time point will be calculated to determine if quality of life is reduced over the course of treatment. Longitudinal techniques will be employed to describe changes over time.

National Cancer Institute (NCI)

Mayo Clinic

Antirheumatic Agents

Anti-Infective Agents

Cyclophosphamide

Immunomodulating Agents

Imiquimod

Immunosuppressive Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Adjuvants, Immunologic

Interferons

TAPA-Pulsed DC Vaccine Cyclophosphamide Pill Imiquimod Topical Cream

Subjects will given the vaccine which contains 1 x 10\^7 TAPA-pulsed dendritic cells and is administered ID. A total of three (3) cycles therapy will be administered weekly.

TAPA-pulsed DC vaccine

Subjects will be given low-dose cyclophosphamide by mouth for 5 days starting 5 to 7 days prior to the vaccine cycle.

Cyclophosphamide Pill

Topical Imiquimod Cream will be applied after vaccination.

Imiquimod Topical Cream

Anthony Tolcher, MD

Patients diagnosed with progressive and/or refractory solid malignancies, who have failed conventional therapy, and have no available, potentially curative therapeutic options, will be candidates for this Phase I/II study. Following confirmation of disease progression and/or refractoriness, eligible patients who agree to participate and sign an informed consent form will have their tumor cells/tissues and/or blood analyzed for the expression of a specific panel of Tumor Associated Peptide Antigens (TAPAs), including Sp17, ropporin, AKAP-4, PTTG1, Span-xb, Her-2/neu, HM1.24, NY-ESO-1 and MAGE-1.

For patients whose tumors express one (1) or more of these TAPAs (Sp17, ropporin, AKAP-4, PTTG1, Span-xb, Her-2/neu, HM1.24, NY-ESO-1 and MAGE-1), whole blood will be obtained by phlebotomy and/or leukapheresis performed for generation of autologous DCs. Patient's DCs will be generated in Kiromic's Cell Processing GMP facility, according to established Standard Operating Procedures, and activated by pulsing/loading them with the TAPA(s) relevant for each particular patient. Patients will receive five (5) days of low-dose cyclophosphamide 5 to 7 days prior to each vaccination with TAPA-pulsed DCs to decrease Treg activity. Patients will also receive a single dose of topical Imiquimod cream after each vaccination. TAPA-pulsed DCs will be administered at a fixed dose of up to 1 X 107 DCs. DC vaccination schedule will be weekly via intradermal (ID) injections for a total of 3 vaccinations. Topical Imiquimod cream will also be administered once after the vaccination. Patients will be followed on a weekly basis (or more frequently if required) to evaluate treatment-related toxicity. Immune efficacy and anti-tumor responses will be evaluated per protocol specifications. Continuation and stopping rules for the study will be defined based on toxicity/tolerability (Phase I) and immune efficacy (Phase II).

Cyclophosphamide, TAPA-Pulsed Dendritic Cell Therapy and Imiquimod in Progressive and/or Refractory Solid Malignancies

Phase I/II Study of Low-Dose Cyclophosphamide, Tumor Associated Peptide Antigen-Pulsed Dendritic Cell Therapy and Imiquimod, in Patients With Progressive and/or Refractory Solid Malignancies

Grade, causality, start/stop dates (duration), resolutions for adverse events will be monitored and recorded.

The response of T-cells present in the peripheral blood mononuclear cells (PBMCs) population to the peptides used to pulse a patient's dendritic cell vaccine is evaluated by measuring the expression of Th1/CTL-type cytokines (IFN-γ and/or TNF-α and/or IL-17) by a standard ELI-Spot assay using 500,000 PBMCs per experimental replicate and a minimum of 3 experimental replicates for each stimulation. The results are expressed as the average number of spots obtained from the stimulation of 500,000 PBMCs

DTH skin test will be performed on subject's forearm or within 5 cm from the site of prior DC vaccination, if possible

Kiromic BioPharma Inc.

TAPA-Pulsed DC Vaccine Cyclophosphamide Pill Imiquimod Topical Cream

TAPA-pulsed DC vaccine: Subjects will given the vaccine which contains 1 x 10\^7 TAPA-pulsed dendritic cells and is administered ID. A total of three (3) cycles therapy will be administered weekly.

Cyclophosphamide Pill: Subjects will be given low-dose cyclophosphamide by mouth for 5 days starting 5 to 7 days prior to the vaccine cycle.

Imiquimod Topical Cream: Topical Imiquimod Cream will be applied after vaccination.

CYP, TAPA-pulsed DC Vaccine, Imiquimod

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

CMO and Head of Clinical Operations

Adverse Events Due to Administration of TAPA-Pulse DC Vaccine

Immune Response

Positive DTH Skin Tests With Relevant TAPA

Overall Study

Glioma

Neoplasms, Neuroepithelial

Neoplasms, Glandular and Epithelial

Gastrointestinal Agents

Amino Acids

Poly I-C

Carboxymethylcellulose Sodium

Poly ICLC

Laxatives

Cathartics

Antiviral Agents

Lysine

Patients undergo leukapheresis 10 days prior to first injection. Patients then receive ppDC ID with poly ICLC IM in both arms Q2W for total 3 doses and then every 6 months for up to 3 doses. Patients undergo MRI throughout the trial. Patients also undergo blood sample collection throughout the trial in addition to stool sample collection during screening and on the trial.

Undergo blood and stool sample collection

Biospecimen Collection

Leukapheresis

Magnetic Resonance Imaging

Sichen Li

Sichen C. Li

Anthony C. Wang, MD

Anthony C Wang, MD

This phase I trial tests the safety and side effects, and best dose of a vaccine (neoantigen-target ppDC) in treating patients with H3 G34-mutant diffuse hemispheric glioma. Vaccines made from the patient's own white blood cells and peptide-pulsed dendritic cells may help the body build an effective immune response to kill tumor cells. Giving neoantigen-targeted ppDC may be safe, tolerable and/or effective in treating patients with diffuse hemispheric glioma with a H3 G34 mutation.

PRIMARY OBJECTIVE:

I. To evaluate the safety and feasibility of neoantigen-targeted ppDC in adult patients with diffuse hemispheric glioma (DHG).

SECONDARY OBJECTIVES:

I. To evaluate the immunogenicity of neoantigen-targeted ppDC in adult patients with DHG.

II. To determine whether neoantigen-targeted ppDC facilitates systemic T cell-mediated adaptive immune activation in DHG patients.

III. To determine whether neoantigen-targeted ppDC facilitates a target-specific anti-tumor T cell expansion in DHG patients.

IV. To determine whether pro-inflammatory phenotypic changes in systemic immune cell populations are detected in peripheral blood in response to neoantigen-targeted ppDC vaccination in DHG patients.

EXPLORATORY OBJECTIVES:

I. To estimate the potential efficacy of neoantigen-targeted ppDC in DHG patients.

II. To correlate physiologic and metabolic magnetic resonance imaging (MRI) with systemic immunologic response after neoantigen-targeted ppDC in DHG patients.

III. To isolate and sequence immunodominant anti-tumor T cell T-cell receptor (TCRs) stimulated by neoantigen-targeted ppDC in DHG patients.

IV. To explore whether study participants demonstrating immune-reactive responses to neoantigen-targeted ppDC harbor significantly different gastrointestinal microbiota profiles in comparison to unresponsive participants.

OUTLINE:

Patients undergo leukapheresis 10 days prior to first injection. Patients then receive ppDC intradermally (ID) with poly ICLC intramuscularly (IM) in both arms every 2 weeks (Q2W) for total 3 doses and then every 6 months for up to 3 doses. Patients undergo magnetic resonance imaging (MRI) throughout the trial. Patients also undergo blood sample collection throughout the trial in addition to stool sample collection during screening and on the trial.

After completion of study treatment, patients are followed up at 30 and 120 days and then up to 24 months.

A Vaccine (Neoantigen-Targeted ppDC) for the Treatment of H3 G34-mutant Diffuse Hemispheric Glioma

A Pilot Study to Evaluate the Safety and Feasibility of Neoantigen-Targeted Dendritic Cell Vaccination in Diffuse Hemispheric Glioma, H3 G34-Mutant

Will be graded in severity according to Common Terminology Criteria for Adverse Events version 5.0 (CTCAE, v 5.0) guidelines, monitoring for 30 days following each dose for adverse event recording, and for 120 days following each dose for serious adverse event recording.

Peripheral blood mononuclear cells (PBMCs) will be evaluated by ribonucleic acid sequence for significant increase in gamma-interferon (IFN) gene expression signature, comparing baseline PBMCs with PBMCs obtained after each dose phase of peptide-pulsed dendritic cells (ppDC).

PBMCs obtained before and after each ppDC dose phase will be analyzed for significant clonal T cell expansion by bulk V beta-T cell receptor (TCR) sequencing.

The targets of clonal cytotoxic T cell expansion in PBMCs in response to ppDC assessed by using target-specific major histocompatibility complex (MHC) oligomers binding assays.

The pro-inflammatory phenotypic changes in immune cell populations in response to ppDC assessed by cellular indexing of transcriptomes, epitopes-sequencing and a multi-color fluorescence-activated cell sorting panel.

The changes in immune cell subset expansion and contraction in T cell and myeloid-derived cell populations in response to ppDC assessed by cellular indexing of transcriptomes and epitopes-sequencing and a multi-color fluorescence-activated cell sorting panel.

The profile changes of the markers for immune cell activity, suppression, and exhaustion in T cell and myeloid-derived cell populations in response to ppDC assessed by cellular indexing of transcriptomes and epitopes-sequencing and a multi-color fluorescence-activated cell sorting panel.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
mRNA Electroporated Autologous Dendritic Cells for Stage III/IV Melanoma	NCT01676779	Malignant Melan... Malignant Melan...	Dendritic cell ...	18 Years -	Universitair Ziekenhuis Brussel
Dendritic Cell Therapy, Cryosurgery, and Pembrolizumab in Treating Patients With Non-Hodgkin Lymphoma	NCT03035331	Aggressive Non-... Indolent Non-Ho... Recurrent Diffu... Recurrent Folli... Recurrent Mantl... Recurrent Margi... Recurrent Non-H... Recurrent Prima... Recurrent T-Cel... Small Lymphocyt...	Cryosurgery Dendritic Cell ... Laboratory Biom... Pembrolizumab Pneumococcal 13... Quality-of-Life...	18 Years -	Mayo Clinic
Cyclophosphamide, TAPA-Pulsed Dendritic Cell Therapy and Imiquimod in Progressive and/or Refractory Solid Malignancies	NCT02224599	Progressive Sol... Refractory Soli... Cancer	TAPA-pulsed DC ... Cyclophosphamid... Imiquimod Topic...	-	Kiromic BioPharma Inc.
A Vaccine (Neoantigen-Targeted ppDC) for the Treatment of H3 G34-mutant Diffuse Hemispheric Glioma	NCT06342908	Diffuse Hemisph...	Biospecimen Col... Dendritic Cell ... Leukapheresis Magnetic Resona... Poly ICLC	18 Years - 50 Years	Jonsson Comprehensive Cancer Center

Spots Global Cancer Trial Database for dendritic cell therapy