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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT02362464

Collaborator

(none)

Enrollment

Location

Arm

82.4

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 TARP peptide vaccinations.

Eligibility:

Men who took part in 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.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms Neoplasms of Prostate Prostate Cancer Cancer Of Prostate Stage D0 Prostate Cancer	Biological: ME TARP vaccine	Phase 2

Detailed Description

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 (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 (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- >= 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 cell helper epitopes that will allow generation of better 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: ECOG 0-1 and life expectancy greater than or equal to 1 year.
Hemoglobin greater than or equal to 10.0 gm/dL, WBC greater than or equal to 2,500/mm3, ALC greater than or equal to 500/ mm3, ANC greater than or equal to 1,000/mm3, platelet

count greater than or equal to 100,000/mm3, and PT/PTT less than or equal to 1.5X ULN unless receiving clinically indicated anticoagulant therapy; SGPT/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 GFR (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); 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 patient s 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 DC vaccine: 20

x106 viable cells/dose) delivered intradermally at Weeks 3, 6, 9, 12, 15, and 24.

Study Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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.

Actual Study Start Date :

May 12, 2015

Actual Primary Completion Date :

Mar 25, 2022

Actual Study Completion Date :

Mar 25, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 intradermally given vaccine given at weeks 3, 6, 9, 12, 15 and 24.	Biological: ME 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.

Arm

Intervention/Treatment

Experimental: 1

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

Biological: ME 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.

Outcome Measures

Primary Outcome Measures

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. [Up to 30 days after week 24 vaccination]
The quantity of AEs each subject experiences at least possibly related to the vaccine treatment.

Secondary Outcome Measures

assess and compare the change in slope log PSA from pre-study baseline (-12 months to entry on the current study) to the changein slope log PSA at weeks 3-24 and 3-48 post ME TARP vaccination [weeks 3-24 and 3-48 post ME TARP vaccination]
change in slope log PSA
compare the change in slope log PSA versus the same change in slope log PSA parameters following 1st generation TARP vaccination on protocol 09-C-0139 [at weeks 3-24 and 3-48 following ME TARP vaccination]
change in slope log PSA
assess reactivity to WT27-35 and EE29-37-9V TARP peptides [Week 24 and Week 48 following immunization with the 2nd generation ME TARP]
measure of reactivity
compare TARP WT27-35 and EE29-37-9V TARP peptide IFN-? ELISPOT reactivity [Week 24 and 48 following ME TARP vaccination]
characteristics of WT27-35 and EE29-37-9V TARP peptide IFN-gamma ELISPOT reactivity

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

INCLUSION CRITERIA:
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: ECOG 0-1, life expectancy of greater than or equal to 1 year.
Hemoglobin greater than or equal to 10.0 gm/dL, WBC greater than or equal to 2,500/mm3, ALC greater than or equal to 500/mm3, ANC greater than or equal to 1,000/mm3, platelet count greater than or equal to 100,000/mm3.
PT/PTT less than or equal to 1.5X ULN unless receiving clinically indicated anticoagulant therapy.
SGOT/SGPT less than or equal to 2.5X ULN, total bilirubin less than or equal to 1.5X ULN, Cr less than or equal to 1.5X ULN, estimated GFR (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.
HIV negative
No use of investigational agents within 4 weeks of study enrollment or use of immunosuppressive or immunomodulating agents (including IVIG) within 8 weeks of study entry. Note: Use of topical, inhaled and intranasal steroid therapy is permitted.
Greater than or equal to 6 weeks since the receipt of chemotherapy or radiation therapy.
Standard of care medical management of current prostate cancer disease status by the patient s local oncologist, e.g. androgen deprivation therapy is allowed.
Able to understand and provide Informed Consent.
Must be able and willing to adhere to protocol requirements, visits and vaccination

timeline.

EXCLUSION CRITERIA:

Patients with a second malignancy requiring active treatment.
Patients with an active infection.
Patients on immunosuppressive therapy including:

--Systemic corticosteroid therapy for any reason. Patients receiving inhaled, intranasal or topical corticosteroids may participate.

Other significant or uncontrolled medical illness. Patients with a remote history of or active mild asthma may participate.
Patients who, in the opinion of the Principal Investigator, have significant medical or psychosocial problems that warrant exclusion including:
Other serious non-malignancy-associated medical conditions that may be expected to limit life expectancy to less than 2 years.
Any condition- medical, psychiatric or otherwise, that would preclude informed consent, consistent follow-up or compliance with any aspect of the study.