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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 Pancreatic Cancer

Phase 1/Phase 2
18 Years
Not Enrolling
Pancreatic Cancer

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Trial Information

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

According to statistics of the American Cancer Society, an estimated 31,000 individuals will
be diagnosed with pancreatic cancer and 25,000 will die of the disease, making it the fifth
leading cause of U.S. cancer deaths this year despite all current therapy. This protocol
attempts to exploit an approach to pancreatic cancer immunotherapy using a naturally
occurring barrier to xenotransplantation in humans in an attempt to vaccinate patients
against their pancreatic 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 surgically
resected pancreatic cancer will undergo a series of twelve intradermal injections with a
vaccine composed of irradiated allogeneic pancreatic cancer cell lines (HAPa-1 and HAPa-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:

- A histological diagnosis of adenocarcinoma or other exocrine carcinoma of the
pancreas. The patient's pathology must be reviewed and confirmed by Northwestern
University's Pathology Department.

- AJCC Stage I or II Pancreatic carcinoma. Patients must have undergone surgical
resection for the tumor.

- Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2.

- Serum albumin greater than or equal to 2.5 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.

- 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.

- Adequate organ function including:

Marrow: hemoglobin greater than or equal to 10.0 gm/dL, absolute granulocyte count (AGC)
greater than or equal to 1500/mm3, platelets greater than or equal to 100,000/mm3,
absolute lymphocyte count greater than or equal to 475/mm3.

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

Renal: serum creatinine (sCr) less than or equal to 2.0 x ULN, or creatinine clearance
(Ccr) greater than or equal to 30 mL/min.

- Prior therapy for pancreatic cancer that may include surgery and/or different
neoadjuvant chemotherapy or adjuvant chemo-radiation regimens, or radiation therapy.
Patients who undergo surgical resection and refuse chemotherapy or radiation therapy
will be eligible.

- Patients must be greater than or equal to 4 weeks since surgery if treated with
neoadjuvant therapy or greater than or equal to 4 weeks since conclusion of
chemo-radiation if treated with post-operative adjuvant therapy and recovered from
the toxicity of prior treatment to less than or equal to Grade I, exclusive of
alopecia or fatigue.

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

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

Exclusion Criteria:

- Age <18-years-old.

- Active metastases.

- Hypercalcemia > 2.9 mmol/L, unresponsive to standard therapy (e.g., I.V. hydration,
diuretics, calcitonin or bisphosphonate therapy).

- Other malignancy within five years, unless the probability of recurrence of the prior
malignancy is <5%. Patient's 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 five years are also eligible for this study.

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

- Subjects taking systemic corticosteroid therapy for any reason are not eligible.
Subjects receiving inhaled or topical corticosteroids are eligible. Subjects who
require systemic corticosteroids after beginning vaccination, will be removed from

- Significant or uncontrolled congestive heart failure (CHF), 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 > 38.1C).

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

- Other serious medical conditions that may be expected to limit life expectancy to
less than 2 years (e.g., liver cirrhosis) or a serious illness in medical opinion of
the clinical investigator.

- 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.

- Prior splenectomy.

- Pregnant or nursing women due to the unknown effects of vaccination on the developing
fetus or newborn infant. (For patients with child bearing potential, a βHCG must be
completed within 7 days of first vaccination).

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:

To assess the side effects, dose-limiting toxicity and maximum tolerated dose.

Outcome Time Frame:

6 months

Principal Investigator

Mary Mulcahy, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Northwestern University


United States: Food and Drug Administration

Study ID:




Start Date:

November 2005

Completion Date:

September 2007

Related Keywords:

  • Pancreatic Cancer
  • Pancreatic Neoplasms



Northwestern UniversityChicago, Illinois  60611