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A Phase I/II Study of Autologous Dendritic Cells Pulsed With Apoptotic Tumor Cells (DC/LNCaP) Administered Subcutaneously to Prostate Cancer Patients.

Phase 1/Phase 2
18 Years
Not Enrolling
Prostate Cancer

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Trial Information

A Phase I/II Study of Autologous Dendritic Cells Pulsed With Apoptotic Tumor Cells (DC/LNCaP) Administered Subcutaneously to Prostate Cancer Patients.

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.

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


- 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


- At least 4 weeks since radiotherapy


- 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.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Outcome Measure:

Adverse Event

Outcome 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.

Outcome Time Frame:

End of blinded phase (wk 9)

Safety Issue:


Principal Investigator

Robert B. Darnell, MD, PHD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Rockefeller University


United States: Food and Drug Administration

Study ID:

RDA 0466



Start Date:

March 2002

Completion Date:

November 2008

Related Keywords:

  • Prostate Cancer
  • Prostatic Neoplasms



Rockefeller University Hospital New York, New York  10021-6399