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A Phase I/II Study of an Antitumor Vaccination Using Alpha (1,3) Galactosyltransferase Expressing Allogeneic Tumor Cells in Patients With Hormone Refractory Prostate Cancer

Phase 1/Phase 2
19 Years
Not Enrolling
Prostate Cancer

Thank you

Trial Information

A Phase I/II Study of an Antitumor Vaccination Using Alpha (1,3) Galactosyltransferase Expressing Allogeneic Tumor Cells in Patients With Hormone Refractory Prostate Cancer

Prostate cancer is the most common type of cancer found in American men, other than skin
cancer. The American Cancer Society estimated that there were about 230,900 new cases of
prostate cancer in the United States in the year 2004. About 29,900 men will die of this
disease. Prostate cancer is the second leading cause of cancer death in men, exceeded only
by lung cancer. This protocol attempts to exploit an approach to prostate cancer
immunotherapy using a naturally occurring barrier to xenotransplantation in humans in an
attempt to vaccinate patients against their prostate cancer. The expression of the murine
alpha (1,3) galactosyltransferase [alpha (1,3) GT] gene results in the cell surface
expression of alpha (1,3) galactosyl-epitopes (alpha-gal) on membrane glycoproteins and
glycolipids. These epitopes are the major target of the hyperacute rejection response that
occurs when organs are transplanted from non-primate donor species into man. Human hosts
often have pre-existing anti-alpha-gal antibodies that bind alpha-gal epitopes and lead to
rapid activation of complement and cell lysis. The pre-existing anti-alpha-gal antibodies
found in most individuals are thought to be due to exposure to alpha-gal epitopes that are
naturally expressed on normal gut flora leading to chronic immunological stimulation. These
antibodies may comprise up to 1% of serum IgG. In this Phase I/II trial, patients with
hormone refractory prostate cancer will undergo a series of twelve intradermal injections
with a vaccine composed of irradiated allogeneic prostate cancer cell lines (HAP-1 and
HAP-2) that have been transduced with a recombinant Moloney murine leukemia virus
(MoMLV)-based retroviral vector expressing the murine alpha (1,3) GT gene. Endpoints of the
study include determination of dose-limiting toxicity (DLT), maximum tolerated dose (MTD),
tumor and immunological responses.

Inclusion Criteria:

- Phase I and Phase II Arm A: A histological diagnosis of prostate cancer with evidence
of metastatic disease by CT scan or bone scan. Phase II, Arm B: Evidence of hormone
refractive progressive disease by increasing PSA only.

- For patients enrolling in Phase II, Arm B: refractory to hormone therapy defined by:
two consecutive increases in PSA documented over a previous reference value, the
first occurring a minimum of 1 week from the reference value, with one value of at
least 4 ng/mL and the increase(s) must be by at least 1.0 ng/mL.

- Castrate testosterone levels < 50 ng/dl (0.50 ng/mL)

- AJCC Stage IV (any T, any N, M1), hormone refractory metastatic, progressive or
recurrent prostate carcinoma. Patients must have failed one attempt at hormonal
therapy and may have received 2 prior chemotherapy regimens.

- ECOG performance status less than or equal to 2.

- Serum albumin greater than or equal to 3.0 gm/dL.

- Expected survival greater than or equal to 6 months.

- Subjects must have a negative serology for Hep B, C, and HIV prior to entering study.

- Adequate organ function including:

Marrow: *Hemoglobin greater than or equal to 10.0 mg/dL, *absolute granulocyte count (AGC)
greater than or equal to 1,500/mm(3), *platelets greater than or equal to 100,000/mm(3),
*absolute lymphocyte count greater than or equal to 475/mm(3).

Hepatic: *serum total bilirubin less than or equal to 1.5 x upper limit of normal (ULN),
*ALT (SGPT) and AST (SGOT) less than or equal to 2.5 x ULN.

Renal: *serum creatinine less than or equal to 2.0 x ULN or creatinine clearance greater
than or equal to 30 mL/min.

- All on-study tests must be less than or equal to Grade I toxicity for patient to be
eligible for study, excluding serum LDH levels. PT, PTT must be less than or equal to
1.5 x ULN except for patients who are on therapeutic anticoagulant therapy.

- Measurable or bone metastases (Phase I, Phase II-Arm A) or non-measurable disease
(Phase II-Arm B).

- Patients must have been treated with hormonal therapy and may have been treated with
surgery and/or radiation therapy and/or less than or equal to 2 different
chemotherapy regimens (including neoadjuvant and adjuvant treatment).

- Patients must be greater than or equal to 4 weeks since major surgery, radiotherapy,
chemotherapy (6-weeks if they were treated with a nitrosourea or mitomycin) and
recovered from the toxicity of prior treatment to less than or equal to Grade 1,
exclusive of alopecia or fatigue.

- Patients must have the ability to understand the study, its risks, side effects,
potential benefits and is able to give written informed consent to participate.
Patients may not be consented by a durable power of attorney (DPA).

- Male subjects of child producing potential must agree to use contraception or
avoidance of pregnancy measures while enrolled on study and receiving the
experimental drug, and for one month after the last immunization.

- Patients taking bisphosphonates at the time of registration into the trial are
eligible, but bisphosphonates must be continued at a constant level throughout the
trial period. Bisphosphonate use must be initiated at least 28 days prior to first

Exclusion Criteria:

- Age less than 19 years of age.

- Active CNS metastases or carcinomatous meningitis.

- Hypercalcemia greater than 2.9 mmol/L, unresponsive to standard therapy.

- Other malignancy within last 5 years, unless the probability of recurrence of the
prior malignancy is less than 5%. Patients curatively treated for squamous and basal
cell carcinoma of the skin or patients with a history of malignant tumor in the past
that have been disease free for at least 5 years are also eligible for this study.

- History of organ transplant or active immunosuppressive therapy (such as
cyclosporine, tacrolimus, etc.).

- Subjects taking systemic corticosteroid therapy for any reason are not eligible.

- Significant or uncontrolled congestive heart failure, myocardial infarction or
significant ventricular arrhythmias within the last six months.

- Active infection or antibiotics within 1-week prior to study, including unexplained
fever (temp. greater than 38.1 degrees Celsius).

- Autoimmune disease (e.g., systemic lupus erythematosis, active rheumatoid arthritis,
etc). Patients with a remote history of asthma or mild active asthma are eligible.

- Other serious medical conditions that may be expected to limit life expectancy to
less than 2 years (e.g., liver cirrhosis).

- Any condition, psychiatric or otherwise, that would preclude informed consent,
consistent follow-up or compliance with any aspect of the study (e.g., untreated
schizophrenia or other significant cognitive impairment, etc).

- A known allergy to any component of the alpha (1,3) galactosyltransferase tumor
vaccine or cell lines from which it is derived.

- Concurrent therapy such as palliative radiation or opioid analgesics for
tumor-associated pain.

- Anti-androgen therapy within 42 days of first treatment.

- Treatment with cimetidine within 30 days of first treatment.

- Prior splenectomy.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety and efficacy of administration of HyperAcute-Prostate (HAP) cancer cells by injection into men with hormone refractory prostate carcinoma

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Charles J. Link, M.D.

Investigator Role:

Study Chair

Investigator Affiliation:

NewLink Genetics Corporation


United States: Food and Drug Administration

Study ID:




Start Date:

March 2005

Completion Date:

September 2007

Related Keywords:

  • Prostate Cancer
  • Prostatic Neoplasms



University of Nebraska Medical Center Omaha, Nebraska  68198-3330