Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

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Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Vaccines

Intradermally given vaccine given at weeks 3, 6, 9, 12, 15 and 24.

dose of 20 x 10\^6 viable cells multiepitope TARP dendritic cell vaccine given intradermally at weeks 3, 6, 9, 12, 15 and 24.

Multi-epitope (ME) T-cell Receptor Alternate Reading Frame Protein (TARP) vaccine

Hoyoung M Maeng, M.D.

Background:

- Few studies or literature are available about the long-term safety of repeated peptide vaccinations in people over a period of time. Long-term vaccination may be needed to control tumors. Researchers gave a group of men a series of vaccine injections over 2 years. Now they want to give those same men the new version of the vaccine. They want to see if it produces different types of immune responses and also ensure that repeated vaccinations are safe.

Objectives:

- To find out the long-term safety of repeated T-cell receptor alternate reading frame protein (TARP) peptide vaccinations.

Eligibility:

- Men who took part in National Cancer Institute (NCI) protocol 09-C-0139.

Design:

* Participants will be screened with blood tests, scans, physical exam, medical history, and an evaluation of how well they perform everyday activities.
* Participants will have apheresis. Blood will be removed with a needle from one arm. A machine will separate the white blood cells. The blood, minus the white cells, will be returned through a needle in the other arm.
* Participants will have 14 visits. At each visit, they will have a physical exam and blood tests. They will discuss any side effects.
* Participants will get vaccine injections at weeks 3, 6, 9, 12, 15, and 24. The vaccine will be made from the participants own cells.
* Participants will get a Vaccine Report Card to complete after receiving vaccine.
* The study lasts 96 weeks.

TARP

* T-cell receptor gamma alternate reading frame protein (TARP) is an amino acid protein expressed by both normal and malignant prostate cancer tissue; 95% of prostate cancer specimens are positive for TARP expression. TARP is highly expressed in prostate cancers of all Gleason types, in primary as well as metastatic disease, and in hormone sensitive and castrate resistant prostate cancer. Therefore, TARP is an ideal tumor antigen target for a vaccine.
* A prospective, randomized pilot study of 1st generation TARP Peptide vaccination National Cancer Institute (NCI 09-C- 0139) utilizing TARP WT 27-35 and EE29-37-9V peptides was conducted in HLAA\* 0201positive men with stage D0 prostate cancer prostate specific-antigen (PSA) biochemical recurrence) and a PSA doubling time (PSADT) of greater than or equal to 3 months and less than or equal to 15 months. TARP vaccination was found to be immunogenic, safe and well tolerated, with adverse events limited to injection site reactions less than or equal to Grade 2. TARP vaccination was also associated with a decreased slope log PSA compared to pre-vaccination baseline in 72% of subjects reaching 24 weeks and 74% reaching 48 weeks (p=0.0012 and p=0.0004 for overall changes in slope log PSA, respectively); TARP vaccination also resulted in a 50% decrease in calculated tumor growth rate constant: prevaccine g = 0.0042/day, post-vaccine g = 0.0021/day (p=0.003); TARP-specific IFN- \>= enzyme-linked immunosorbent spot (ELISPOT) responses were detected in the majority of subjects but did not correlate with decreases in slope log (PSA).

Multi-Epitope (ME) TARP Vaccine

* The vaccine platform includes the original two 9-mer HLA-A\*0201 binding TARP peptide epitopes (WT27-35 and EE29-37-9V) utilized in NCI 09-C-0139 as well as an additional five 20-mer TARP peptides overlapping by 10 amino acids for a total of 7 peptides that span the amino acid sequence of the entire TARP protein.
* The advantage of this multi-epitope TARP peptide vaccine platform is that the overlapping epitopes cover the entire TARP protein, resulting in potential for induction of a multi-valent anti-TARP response. In addition, these longer synthetic peptides include TARP-specific MHC class II CD4 T lymphocytes (CD4+ T) cell helper epitopes that will allow generation of better cyctotoxic T cells (CD8+ T) cell responses with improved functional avidity and longevity as well as humoral anti-TARP antibody responses.

Study Objectives

Primary Objective:

-To assess the long-term safety of repeated TARP peptide vaccination following the use of a 1st generation bivalent (09-C-0139) and a 2nd generation ME TARP peptide vaccine. Specifically, to document if less than 10% of enrolled patients experience a vaccine-related Grade 3 adverse event (local injection site reactions or systemic reactions).

Eligibility Criteria All Patients

* Males greater than or equal to 18 years of age with histologically confirmed adenocarcinoma of the prostate.
* Prior enrollment in NCI protocol 09-C-0139 with receipt of at least 5 doses of TARP peptide vaccine (i.e. completion of primary vaccination series).
* Performance Status: Eastern Cooperative Oncology Group (ECOG) 0-1 and life expectancy greater than or equal to 1 year.
* Hemoglobin greater than or equal to 10.0 gm/dL, white blood cell (WBC) greater than or equal to 2,500/mm\^3, ALC greater than or equal to 500/ mm\^3, absolute neutrophil count (ANC) greater than or equal to 1,000/mm\^3, platelet

count greater than or equal to 100,000/mm\^3, and prothrombin time (PT)/partial thromboplastin time (PTT) less than or equal to 1.5X upper limit of normal (ULN) unless receiving clinically indicated anticoagulant therapy; serum glutamate-pyruvate transaminase (SGPT)/serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 2.5X ULN, total bilirubin less than or equal to 1.5X ULN; creatinine less than or equal to 1.5X ULN and estimated glomerular filtration rate (eGFR) greater than or equal to 60 ml/min.

* Hepatitis B and C negative (unless the result is consistent with prior vaccination or prior infection with full recovery); human immunodeficiency virus (HIV) negative.
* No use of investigational agents within 4 weeks of study enrollment or use of immunosuppressive or immunomodulating agents within 8 weeks of study entry.
* Standard of care medical management of current prostate cancer disease status by the patients local oncologist e.g., androgen deprivation therapy is allowed.
* Must be able/willing to adhere to protocol requirements and vaccination timeline.

Exclusion Criteria All Patients

* Patients with active infection or other significant or uncontrolled medical illness. Patients with a remote history of asthma or active mild asthma may participate.
* Patients on immunosuppressive therapy including systemic corticosteroid therapy for any reason. Patients receiving inhaled or topical corticosteroids may participate.
* Patients who, in the opinion of the Principal Investigator, have significant medical or psychosocial problems that warrant exclusion.

Study Design

* Open label, prospective, non-randomized, long-term follow-up pilot study of 96 weeks to assess the long-term safety of repeated TARP vaccination in patients that have already received the first generation TARP vaccine. Sample size: N equals 40 maximum.
* All patients will undergo an 18L apheresis for mononuclear cell collection at Week 0.
* All patients will receive a total of 6 doses of autologous ME TARP peptide dendritic cell (DC) vaccine: 20x10\^6 viable cells/dose) delivered intradermally at Weeks 3, 6, 9, 12, 15, and 24.

Long-Term TARP Vaccination Using a Multi-Epitope TARP Peptide Autologous Dendritic Cell Vaccination in Previously Vaccinated Men on NCI 09-C-0139

A Pilot Study of Long Term TARP Vaccination Using A Multi-Epitope TARP Peptide Autologous Dendritic Cell Vaccine in Previously Vaccinated Men on NCI 09-C-0139.

All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. All collected IPD will be shared with collaborators under the terms of collaborative agreements.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

The number of Grade 3 adverse events probably related to the vaccine treatment. Adverse events were measured using the Common Terminology Criteria for Adverse Events (CTCAE v.4.0). Grade 3 is severe.

"PSA slope log" was calculated using Memorial Sloan Kettering Cancer Center Prostate Cancer Nomograms (http://nomograms.mskcc.org/Prostate/PsaDoublingTime.aspx) Slope log represents the speed of change of a series of values. Thus, it is reported without any units as it is with a concept of ratio. The clinical meaning of PSA slope change would be decrease or increase of the "speed (velocity)" of changes in PSA, not the changes in PSA values. Decreasing PSA slope after the investigational treatment would mean the PSA rise is slower than pre-treatment baseline. Lowered PSA slope has been reported to show a relationship with was reported as related to improved outcomes.

Participants slope log on study 09C0139 are compared with the slope log values for the same participants after receiving the updated ME-TARP vaccines on the current protocol 15C0076 in participants who were not treated with androgen deprivation. PSA slope log was calculated using Memorial Sloan Kettering Cancer Center Prostate Cancer Nomograms (http://nomograms.mskcc.org/Prostate/PsaDoublingTime.aspx) Slope log represents the speed of change of a series of values. Thus, it is reported without any units as it is with a concept of ratio. The clinical meaning of PSA slope change would be decrease or increase of the "speed (velocity)" of changes in PSA, not the changes in PSA values. Decreasing PSA slope after the investigational treatment would mean the PSA rise is slower than pre-treatment baseline. Lowered PSA slope has been reported to show a relationship with was reported as related to improved outcomes.

Measure of reactivity to WT27-35 and EE29-37-9V TARP peptides.

WT27-35 and EE29-37-9V TARP peptide IFN-gamma ELISPOT reactivity.

National Cancer Institute (NCI)

Principal Investigator

Intradermally given vaccine given at weeks 3, 6, 9, 12, 15 and 24.

Multi-epitope (ME) T-cell Receptor Alternate Reading Frame Protein (TARP) vaccine: dose of 20 x 10\^6 viable cells multiepitope TARP dendritic cell vaccine given intradermally at weeks 3, 6, 9, 12, 15 and 24.

Long Term T-cell Receptor Alternate Reading Frame Protein (TARP) Peptide Vaccinations

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Hoyoung Maeng

Number of Grade 3 Adverse Events (AEs) Probably Related to the Vaccine Treatment

Weeks 3-24

Weeks 3-48

Study participants who were in biochemically recurrent prostate cancer and not exposed to androgen deprivation therapy for the management of prostate cancer were evaluable for this endpoint.

Change in Slope Log PSA From Pre-study Baseline (-12 Months to Entry on the Current Study) to the Change in Slope Log PSA at Weeks 3-24 and 3-48 Post Multi-Epitope (ME) T-cell Receptor Alternate Reading Frame Protein (TARP) Vaccination

PSA slope log of the participants while on previous study 09C0139 at Weeks 3-24

PSA slope log of the participants while on current study 15C0076 at Weeks 3-24

PSA slope log of the participants while on previous study 09C0139 at Weeks 3-48

PSA slope log of the participants while on current study 15C0076 at Weeks 3-48

The participants who were evaluable for Memorial Sloan Kettering Cancer Center Prostate Cancer Nomograms are reported for this outcome measure.

Change in Slope Log Prostate Specific-antigen (PSA) Versus the Same Change in Slope Log PSA Parameters Following 1st Generation T-cell Receptor Alternate Reading Frame Protein (TARP) Vaccination on Protocol 09-C-0139

Assess Reactivity to WT27-35 and EE29-37-9V T-cell Receptor Alternate Reading Frame Protein (TARP) Peptides

TARP WT27-35 and EE29-37-9V T-cell Receptor Alternate Reading Frame Protein (TARP) Peptide Interferon (IFN)-Gamma Enzyme-linked Immunosorbent Spot (ELISpot) Reactivity

Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v.0)

Overall Study

Immunologic Factors

All patients to receive autologous multi-epitope T-cell receptor g alternate reading frame protein (TARP) DC vaccine before randomization

Autologous multi-epitope T-cell receptor g alternate reading frame protein (TARP) DC vaccine after randomization

Autologous elutriated monocyte vaccine placebo after randomization

20x10\^6 viable cells/dose at weeks 3, 6, 9, 12, 15 and 24

Autologus elutriated monocyte placebo vaccine

Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine

Background:

- Men who continue to have an elevated or rising prostate specific antigen (PSA) level after their primary prostate cancer treatment are at increased risk for their cancer to progress. The time it takes to progress is highly variable. One way to predict this progression is based on the change in PSA levels over time. This is called the PSA doubling time (PSADT). Researchers want to test a vaccine on men with Stage D0 prostate cancer. Stage D0 means the PSA has become detectable again or has started to rise after primary treatment, but has not spread to other organs.

Objectives:

- To test a vaccines effectiveness on the rate of PSA increase using PSADT and tumor growth rates.

Eligibility:

- Men with Stage D0 prostate cancer with a PSADT between 3 and 15 months.

Design:

* Participants will be screened with blood tests, scans, physical exam, and medical history. Their prostate cancer will be confirmed.
* Participants will undergo apheresis. Blood will be removed with a needle from one arm. A machine will separate the white blood cells. The blood, minus the white cells, will be returned through a needle in the other arm.
* Participants will have 14 visits. At each visit, they will have a physical exam and blood tests. They will discuss any side effects.
* Participants will get injections of either the vaccine or placebo at weeks 3, 6, 9, 12, 15, and 24. Both will be made from the participants own cells.
* Participants will be selected randomly to receive either active vaccine or placebo. For every two participants assigned to active vaccine, one participant will be assigned to placebo vaccine.
* Participants will get a Vaccine Report Card to to complete after receiving vaccine.
* The study lasts 96 weeks.

TARP

* T-cell receptor g alternate reading frame protein (TARP) is a 58 amino acid protein expressed by both normal and malignant prostate cancer tissue; 95% of prostate cancer specimens are positive for TARP expression. TARP is highly expressed in prostate cancers of all Gleason types, in primary as well as metastatic disease, and in hormone sensitive and castrate resistant prostate cancer. Therefore, TARP is an ideal tumor antigen target for a vaccine.
* A prospective, randomized pilot study of 1st generation TARP Peptide vaccination (National Cancer Institute (NCI) 09-C-0139) utilizing TARP WT 27-35 and EE29-37-9V peptides was conducted in human leukocyte antigen serotype within the HLA-A serotype group (HLA-A 0201) positive men with stage D0 prostate cancer (prostate specific antigen (PSA) biochemical recurrence) and a PSA doubling time (PSADT) of greater than or equal to 3 months and less than or equal to 15 months. TARP vaccination was found to be immunogenic, safe and well tolerated, with adverse events limited to injection site reactions less than or equal to Grade 2. TARP vaccination was also associated with a decreased slope log PSA compared to pre-vaccination baseline in 72% of subjects reaching 24 weeks and 74% reaching 48 weeks (p=0.0012 and p=0.0004 for overall changes in slope log PSA, respectively); TARP vaccination also resulted in a 50% decrease in calculated tumor growth rate constant: pre-vaccine g = 0.0042/day, post-vaccine g = 0.0021/day (p=0.003); TARP-specific interferon gamma (IFN-g) enzyme-linked immune absorbent spot (ELISPOT) responses were detected in the majority of subjects but did not correlate with decreases in slope log (PSA).

Multi-Epitope (ME) TARP Vaccine

* The vaccine platform includes the original two 9-mer HLA-A\*0201 binding TARP peptide epitopes (WT27-35 and EE29-37-9V) utilized in NCI 09-C-0139 as well as an additional five 20-mer TARP peptides overlapping by 10 amino acids for a total of 7 peptides that span the amino acid sequence of the entire TARP protein.
* The advantage of this multi-epitope TARP peptide vaccine platform is that the overlapping epitopes cover the entire TARP protein, resulting in potential for induction of a multi-valent anti-TARP response. In addition, these longer synthetic peptides include TARP-specific major histocompatibility complex (MHC)class II cluster of differentiation 4 (CD4)+ T cell helper epitopes that will allow generation of better cluster of differentiation 8 (CD8)+ T cell responses with improved functional avidity and longevity as well as humoral anti-TARP antibody responses.

Study Objectives:

Primary:

-To assess the difference in the slope log (PSA) for Weeks3-24 minus that formed for the 12 months prior to enrollment on study (referred to as slope324 pre-slope) as well as the slope log (PSA) for weeks 3-48 versus the same pre-treatment slope log (PSA) (referred to as slope 348 preslope) in patients na(SqrRoot) ve to TARP vaccination receiving active, multi-epitope TARP vaccination vs. placebo.

Eligibility:

* Males greater than or equal to 18 years of age with histologically confirmed adenocarcinoma of the prostate.
* Stage D0 disease with documented biochemical progression documented by rising PSA and no evidence of metastatic disease by physical examination, computed tomography (CT) scan or bone scan.
* Prostate specific antigen doubling time (PSADT) greater than or equal to 3 months and less than or equal to 15 months:

  ----Patients must have greater than or equal to 3 PSA measurements over greater than or equal to 3 months.

  --- The interval between PSA measurements must be greater than or equal to 4 weeks.
* Performance Status: Eastern Cooperative Oncology Group (ECOG) 0-1.
* No other concurrent anticancer therapy or prior prostate cancer vaccines expressing TARP.

Study Design:

* Phase II, prospective, single-blinded, randomized, placebo controlled study of 96 weeks duration in men with Stage D0 prostate cancer. Men with a PSADT greater than or equal to 3 months and less than or equal to 15 months will be randomized 2:1 to receive multi-epitope (ME) TARP autologous dendritic cell (DC) vaccination or a control eleutriated monocyte vaccine placebo.
* An initial lead-in of 6 patientswill be enrolled to allow preliminary assessment of the safety of the ME TARP vaccine platform through 12 weeks before enrollment of prospectively randomized subjects blinded to treatment assignment begins.
* All patients will receive a total of 6 doses of vaccine (20 x10(6) viable cells/dose) delivered intradermally at Weeks 3, 6, 9, 12, 15, and 24. All patients will undergo a 15-18L apheresis at Week 0 and restaging at Weeks 48 and 96 to confirm maintenance of Stage D0 disease.

Sample size: N = 72 (6 lead-in patients for safety assessment, 2:1 randomization: TARP N = 44; placebo N =22).

Multi-Epitope TARP Peptide Autologous Dendritic Cell Vaccination in Men With Stage D0 Prostate Cancer

A Randomized, Placebo-Controlled Phase II Study of Multi-Epitope TARP Peptide Autologous Dendritic Cell Vaccination in Men With Stage D0 Prostate Cancer

All IPD recorded in the medical record will be shared with intramural investigators upon request. All collected individual participant data (IPD) will be shared with collaborators under the terms of collaborative agreements.

Here is the number of participants with non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

PSA Doubling Time (PSADT) and slope log (PSA) were calculated at every study visit using the PSADT Memorial Sloane Kettering nomogram. The values were calculated to demonstrate the rate of rise of PSA, expressed as the velocity in nanograms/mL/year, or the PSA doubling time, in months or years. PSA is a tumor marker for prostate cancer and after surgery (undetectable - e.g. \<0.2 ng/mL) or radiation PSA should fall to a very low level when the disease is effectively treated. When PSA increases (\>2.0 ng/mL) after surgery or radiation that could mean recurrence of the disease. If prostate cancer is growing slower or shrinking after the treatment, PSADT can be longer while PSA slope log is shorter as tumor will make less PSA.

PFS is defined as the duration of time from start of vaccine treatment to time of progression or death. Given the study population in biochemically recurrent prostate cancer, progression is defined as 1)"radiographic progression" by computed tomography (CT) or bone scan, 2) prostate-specific antigen doubling time (PSADT) that is 3 month or shorter, 3) PSADT decrease 50% or more compared to enrollment PSADT.

Cohort 1 All patients to receive autologous multi-epitope T-cell receptor g alternate reading frame protein (TARP) DC vaccine before randomization

Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine: 20x10\^6 viable cells/dose at weeks 3, 6, 9, 12, 15 and 24

1/Lead-in T-cell Receptor g Alternate Reading Frame Protein Dendritic Cell (DC) Vaccine Treatment

Cohort 2 Autologous multi-epitope T-cell receptor g alternate reading frame protein (TARP) DC vaccine after randomization

Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine: 20x10\^6 viable cells/dose at weeks 3, 6, 9, 12, 15 and 24

2/Active T-cell Receptor g Alternate Reading Frame Protein Dendritic Cell (DC) Vaccine Treatment

Total

Pre treatment

One participant in the lead in group had no data for week 48 due to other treatment, thus data could not be used. And one participant in the active group had no data for week 3-24 and 3-48 due to other treatment, thus data could not be used.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Long-Term TARP Vaccination Using a Multi-Epitope TARP Peptide Autologous Dendritic Cell Vaccination in Previously Vaccinated Men on NCI 09-C-0139	NCT02362464	Prostatic Neopl... Neoplasms of Pr... Prostate Cancer Cancer Of Prost... Stage D0 Prosta...	Multi-epitope (...	18 Years -	National Institutes of Health Clinical Center (CC)
Multi-Epitope TARP Peptide Autologous Dendritic Cell Vaccination in Men With Stage D0 Prostate Cancer	NCT02362451	Prostatic Neopl... Prostate Cancer	Autologus elutr... Multi-epitope (...	18 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for d0 prostate cancer