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Safety and Effectiveness of a Vaccine for Prostate Cancer That Uses Each Patients' Own Immune Cells.

Primary Purpose

Prostate Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
vaccine vehicle only
DC/LNCaP
Sponsored by
Rockefeller University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria: Disease Characteristics Histologically confirmed prostate carcinoma Progressive, disease required, i.e.: elevated PSA documented to be rising on 3 occasions, either despite castrate testosterone levels (below 50 ng/dl), or after definitive local therapy (prostatectomy or radiation). Prior/Concurrent Therapy -Biologic therapy: Recovered from toxicity of any prior therapy -Chemotherapy: At least 4 weeks since chemotherapy -Endocrine evaluation/therapy 3 rising PSA values at least 2 weeks apart At least 2 weeks since concurrent corticosteroids (other than for replacement therapy for adrenal insufficiency) Medical hormonal therapy to maintain castrate testosterone levels permitted -Radiotherapy: At least 4 weeks since radiotherapy -Surgery: Prior surgery allowed Patient Characteristics Age: 18 and over, able to give written informed consent. Individuals unable to provide informed consent must have consent provided by the legal guardian, or person designated by the subject to give consent on his behalf. Performance status: Karnofsky 70-100% Life expectancy: At least 1 year Hematopoietic: obtained twice, once within 45 days prior to study entry, and again within 72 hours of study entry. WBC greater than 3,800 Absolute neutrophils greater than 1,500 Absolute lymphocytes greater than 500 Platelets greater than 120,000 Hb at least 10 g/dl Hepatic: --Bilirubin less than 2.0 mg/dl OR --SGOT less than 2 x ULN Renal: Creatinine no greater than 2.0 mg/dl OR Creatinine clearance at least 40 ml/min Rheumatologic: --ANA no greater than upper limit of normal, or ANA abnormal in absence of clinical signs of autoimmunity. Rheumatoid factor (RF) no greater than upper limit of normal, or RF abnormal in absence of clinical signs of autoimmunity. Anti-ds DNA no greater than upper limit of normal, or anti ds DNA abnormal in absence of clinical signs of autoimmunity. Immunologic: Influenza serology (assessment made at time of screening). Assessment of DTH response to a standard anergy panel (to include candida, trichophyton and tetanus) or to a Multitest CMI (a disposable kit for DTH testing with standardized preloaded antigens). Endocrine: --TSH, T3, and T4 no greater than upper limit of normal Radiographic: Baseline bone scan Baseline CT or MRI of abdomen and pelvis Exclusion Criteria: Disease Characteristics -No active CNS metastases Prior/Concurrent Therapy Biologic therapy: No prior autologous or allogeneic tumor vaccines No concurrent other immunotherapy Chemotherapy --Not previously treated with more than 2 chemotherapy regimens No concurrent chemotherapy Radiotherapy --No concurrent radiotherapy Patient Characteristics -Cardiovascular: No NYHA class III/IV status No active angina, clinically significant cardiac arrythmia, recent (6 months) myocardial infarction Pulmonary: --No severe debilitating pulmonary disease Other: No active infection requiring antibiotics No active pain requiring chronic opioid analgesics. Not HIV, hepatitis B or hepatitis C virus positive; anti-HIV, HbsAg and Hep C antibody negative No history of hypersensitivity to vaccine components No serious uncontrolled medical illness No currently active second malignancy other than non-melanoma skin cancer (note: a patient is NOT considered to have currently active malignancy if they have completed therapy and are now considered by their physician to be at less than 30% risk for relapse) No history of total lymph node irradiation No history of vasculitis, including but not limited to systemic necrotizing vasculitides (polyarteritis nodosa group), hypersensitivity vasculitis, Wegener's granulomatosis. No history of autoimmune disease. No use of hydroxyurea within 45 days of study entry No receipt of immune modulators or suppressors within 30 days prior to study entry, including but not limited to interferons and thalidomide. No active requirement for corticosteroids; prior use is acceptable. No psychiatric illness or social condition that, in the opinion of the investigator, would interfere with adherence to study requirements. No alcohol or drug use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.

Sites / Locations

  • Rockefeller University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

DC/LNCaP

Arm Description

12 patients in the placebo Arm for 8 weeks followed by DC/LNCAP, DC/LNCaP-M1 and DC/KLH immunizations over 8 weeks.

12 patients, receiving DC/LNCaP, DC/LNCaP-M1 and DC/KLH immunizations over 8 weeks

Outcomes

Primary Outcome Measures

Adverse Event
Occurrence of adverse events (AE) was compared between the placebo and vaccine groups during the blinded phase (the 1st 9 weeks). At the end of this phase, all were unblinded, and those who received placebo crossed over to now receive vaccine. All serious AEs and any other AEs that occurred 5 times or more are reported. The exact binomial test was used to compare the occurrence of each AE between groups.
Immunogenicity of the DC/LNCaP Vaccine. Pre- vs Post-vaccination Bulk T Cell Proliferation (3H Thymidine Incorporation) by Type of Antigen. The "Number" Indicated is the Median Difference of Post-Pre, of Each Antigen Group.
The difference between post minus pre-vaccination bulk T cell proliferation was calculated for each antigen.

Secondary Outcome Measures

Change in PSA Slope, Pre- vs Post-vaccination.
To model the evolution of PSA (in log-scale) during the three study phases (pre-vaccine, vaccine, and post-vaccine phases), a mixed linear spline model was used. Two knots (one at the start of the vaccine phase and the other at the start of the post-vaccine phase) were used to directly quantify the differences in slopes between each phase. To account for the heterogeneous treatment effect and the repeated measures structure, random effects are incorporated into the model. For the general model, random effects for the intercept, slope and the first knot were considered.

Full Information

First Posted
February 7, 2006
Last Updated
January 11, 2013
Sponsor
Rockefeller University
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1. Study Identification

Unique Protocol Identification Number
NCT00289341
Brief Title
Safety and Effectiveness of a Vaccine for Prostate Cancer That Uses Each Patients' Own Immune Cells.
Official Title
A Phase I/II Study of Autologous Dendritic Cells Pulsed With Apoptotic Tumor Cells (DC/LNCaP) Administered Subcutaneously to Prostate Cancer Patients.
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
March 2002 (undefined)
Primary Completion Date
November 2008 (Actual)
Study Completion Date
November 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rockefeller University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to assess the safety and activity of a type of vaccine as immune therapy for prostate cancer. This vaccine will be made for each participant's own immune cells (called dendritic cells) obtained by blood donation. Dendritic cells are immune cells, whose role is to identify foreign antigens (bacteria, viruses, or tumor cells, for example) in the body and to activate other cells of the immune system to mount an attack on that foreign antigen. Each participant will be randomized into either Arm 1 (experimental treatment only) or Arm 2 (placebo first, then the experimental treatment). Participants will be given the vaccine and three boosters as an injection. After the placebo phase, each participant in Arm 2 will crossover to the treatment phase so that all participants will eventually receive the experimental treatment.
Detailed Description
This is a Phase I/II dendritic cell vaccine study for patients with prostate cancer. Our laboratory has demonstrated that effective tumor immunity in humans is associated with, and likely mediated at least in part by tumor antigen-specific killer T cells (Albert et al., 1998a; Darnell, 1999; Darnell and Posner, 2003). Moreover, we have demonstrated that apoptotic material derived from dying tumor cells are a potent means of delivering antigen to DCs and subsequently triggering tumor antigen-specific T cell responses ex vivo (Albert et al., 1998a; Albert et al., 1998c). In this study, patients with 3 consecutive rises in PSA measured at least 2 week apart, after definite local therapy (prostatectomy or radiation) will be recruited. Peripheral blood monocytes will be collected by leukapheresis and dendritic cells will be generated in the Cleanroom in the Laboratory of Molecular Neuro-Oncology. These dendritic cells will be pulsed with apoptotic prostate cancer cells from a cell line (LNCaP), harvested, tested for certain release criteria, and then injected as vaccine. When patients are found to be eligible for the study, they will be randomized into either the experimental group or the placebo group for the purposes of comparing adverse events between groups only. Vaccine plus 3 boosters (or placebo) will be given, each two weeks apart. After the third booster, patients will be unblinded. Those receiving the vaccine will when enter the follow up phase which includes a post treatment leukapheresis. Those in the placebo group will cross over and receive the vaccine and boosters. The primary outcomes to be evaluated are toxicity and activity. Patients will be evaluated for both local and systemic toxicity. For activity, we measure both immunological and clinical responses to the vaccine, comparing measures taken before and after vaccination, combining patients in both arms.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
12 patients in the placebo Arm for 8 weeks followed by DC/LNCAP, DC/LNCaP-M1 and DC/KLH immunizations over 8 weeks.
Arm Title
DC/LNCaP
Arm Type
Experimental
Arm Description
12 patients, receiving DC/LNCaP, DC/LNCaP-M1 and DC/KLH immunizations over 8 weeks
Intervention Type
Biological
Intervention Name(s)
vaccine vehicle only
Intervention Description
Subcutaneous injection of vaccine vehicle only (5% DMSO in normal saline), followed by cross-over to Arm 1 design.
Intervention Type
Biological
Intervention Name(s)
DC/LNCaP
Intervention Description
Subcutaneous injection of DC/LNCaP, DC/LNCaP-M1, DC/KLH
Primary Outcome Measure Information:
Title
Adverse Event
Description
Occurrence of adverse events (AE) was compared between the placebo and vaccine groups during the blinded phase (the 1st 9 weeks). At the end of this phase, all were unblinded, and those who received placebo crossed over to now receive vaccine. All serious AEs and any other AEs that occurred 5 times or more are reported. The exact binomial test was used to compare the occurrence of each AE between groups.
Time Frame
End of blinded phase (wk 9)
Title
Immunogenicity of the DC/LNCaP Vaccine. Pre- vs Post-vaccination Bulk T Cell Proliferation (3H Thymidine Incorporation) by Type of Antigen. The "Number" Indicated is the Median Difference of Post-Pre, of Each Antigen Group.
Description
The difference between post minus pre-vaccination bulk T cell proliferation was calculated for each antigen.
Time Frame
pre- vs post-vaccination. Pre-vaccination T cells were collected at Wk 0 and post-vaccination T cells were collected at Wk 13
Secondary Outcome Measure Information:
Title
Change in PSA Slope, Pre- vs Post-vaccination.
Description
To model the evolution of PSA (in log-scale) during the three study phases (pre-vaccine, vaccine, and post-vaccine phases), a mixed linear spline model was used. Two knots (one at the start of the vaccine phase and the other at the start of the post-vaccine phase) were used to directly quantify the differences in slopes between each phase. To account for the heterogeneous treatment effect and the repeated measures structure, random effects are incorporated into the model. For the general model, random effects for the intercept, slope and the first knot were considered.
Time Frame
pre- vs post- vaccination PSA slopes.

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Disease Characteristics Histologically confirmed prostate carcinoma Progressive, disease required, i.e.: elevated PSA documented to be rising on 3 occasions, either despite castrate testosterone levels (below 50 ng/dl), or after definitive local therapy (prostatectomy or radiation). Prior/Concurrent Therapy -Biologic therapy: Recovered from toxicity of any prior therapy -Chemotherapy: At least 4 weeks since chemotherapy -Endocrine evaluation/therapy 3 rising PSA values at least 2 weeks apart At least 2 weeks since concurrent corticosteroids (other than for replacement therapy for adrenal insufficiency) Medical hormonal therapy to maintain castrate testosterone levels permitted -Radiotherapy: At least 4 weeks since radiotherapy -Surgery: Prior surgery allowed Patient Characteristics Age: 18 and over, able to give written informed consent. Individuals unable to provide informed consent must have consent provided by the legal guardian, or person designated by the subject to give consent on his behalf. Performance status: Karnofsky 70-100% Life expectancy: At least 1 year Hematopoietic: obtained twice, once within 45 days prior to study entry, and again within 72 hours of study entry. WBC greater than 3,800 Absolute neutrophils greater than 1,500 Absolute lymphocytes greater than 500 Platelets greater than 120,000 Hb at least 10 g/dl Hepatic: --Bilirubin less than 2.0 mg/dl OR --SGOT less than 2 x ULN Renal: Creatinine no greater than 2.0 mg/dl OR Creatinine clearance at least 40 ml/min Rheumatologic: --ANA no greater than upper limit of normal, or ANA abnormal in absence of clinical signs of autoimmunity. Rheumatoid factor (RF) no greater than upper limit of normal, or RF abnormal in absence of clinical signs of autoimmunity. Anti-ds DNA no greater than upper limit of normal, or anti ds DNA abnormal in absence of clinical signs of autoimmunity. Immunologic: Influenza serology (assessment made at time of screening). Assessment of DTH response to a standard anergy panel (to include candida, trichophyton and tetanus) or to a Multitest CMI (a disposable kit for DTH testing with standardized preloaded antigens). Endocrine: --TSH, T3, and T4 no greater than upper limit of normal Radiographic: Baseline bone scan Baseline CT or MRI of abdomen and pelvis Exclusion Criteria: Disease Characteristics -No active CNS metastases Prior/Concurrent Therapy Biologic therapy: No prior autologous or allogeneic tumor vaccines No concurrent other immunotherapy Chemotherapy --Not previously treated with more than 2 chemotherapy regimens No concurrent chemotherapy Radiotherapy --No concurrent radiotherapy Patient Characteristics -Cardiovascular: No NYHA class III/IV status No active angina, clinically significant cardiac arrythmia, recent (6 months) myocardial infarction Pulmonary: --No severe debilitating pulmonary disease Other: No active infection requiring antibiotics No active pain requiring chronic opioid analgesics. Not HIV, hepatitis B or hepatitis C virus positive; anti-HIV, HbsAg and Hep C antibody negative No history of hypersensitivity to vaccine components No serious uncontrolled medical illness No currently active second malignancy other than non-melanoma skin cancer (note: a patient is NOT considered to have currently active malignancy if they have completed therapy and are now considered by their physician to be at less than 30% risk for relapse) No history of total lymph node irradiation No history of vasculitis, including but not limited to systemic necrotizing vasculitides (polyarteritis nodosa group), hypersensitivity vasculitis, Wegener's granulomatosis. No history of autoimmune disease. No use of hydroxyurea within 45 days of study entry No receipt of immune modulators or suppressors within 30 days prior to study entry, including but not limited to interferons and thalidomide. No active requirement for corticosteroids; prior use is acceptable. No psychiatric illness or social condition that, in the opinion of the investigator, would interfere with adherence to study requirements. No alcohol or drug use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert B. Darnell, MD, PHD
Organizational Affiliation
Rockefeller University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rockefeller University Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
25475068
Citation
Frank MO, Kaufman J, Parveen S, Blachere NE, Orange DE, Darnell RB. Dendritic cell vaccines containing lymphocytes produce improved immunogenicity in patients with cancer. J Transl Med. 2014 Dec 5;12:338. doi: 10.1186/s12967-014-0338-3.
Results Reference
derived
PubMed Identifier
20824184
Citation
Frank MO, Kaufman J, Tian S, Suarez-Farinas M, Parveen S, Blachere NE, Morris MJ, Slovin S, Scher HI, Albert ML, Darnell RB. Harnessing naturally occurring tumor immunity: a clinical vaccine trial in prostate cancer. PLoS One. 2010 Sep 1;5(9):e12367. doi: 10.1371/journal.pone.0012367.
Results Reference
derived

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Safety and Effectiveness of a Vaccine for Prostate Cancer That Uses Each Patients' Own Immune Cells.

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