Local Modulation of Immune Receptors to Enhance the Response to Dendritic Cell Vaccination in Metastatic Melanoma

Stopped early · Phase 1

Conditions studied: Metastatic Melanoma

In brief

Our proposed study is designed to test the safety of a new vaccine against melanoma. The induction of immune activity against cancers such as melanoma is a promising approach to cancer treatment, but to date, only a few clinically significant immune responses have been seen following vaccine therapy. This is an important problem, since there are very limited treatment options for patients with metastatic melanoma (melanoma that has spread to lymph nodes and organs). Studies suggest that monoclonal antibodies (mAbs) that block inhibitory receptors on immune cells can enhance the immune responses against cancer, but the intravenous injection of such mAbs has caused severe side effects in animals and humans. In our laboratory, we have developed a method to deliver mAbs and other proteins that block such inhibitory receptors locally at the site where immune responses against melanoma proteins are stimulated by vaccination, enhancing anti-melanoma immunity while avoiding the side-effects associated with intravenous injection of these immune modulators. This is achieved by loading dendritic cells, a type of immune cell, with RNA that encodes the immune modulator. The RNA-loaded dendritic cells then make the immune modulatory proteins and release them locally. By mixing these dendritic cells with additional dendritic cells loaded with melanoma proteins, the immune modulators are released at the site where anti-melanoma immune cells are stimulated. In this phase I trial, subjects with metastatic melanoma will undergo the process of leukapheresis, in which white blood cells are removed from the body. Monocytes, a type of immune cell, will then be purified from the white blood cells and cultured under conditions that will change them into dendritic cells. Half of these dendritic cells are then loaded with melanoma antigen RNA, which will lead to the production of melanoma antigen proteins within the dendritic cells. The remaining half of the dendritic cells will be either untreated or loaded with RNA encoding immune modulators so that these dendritic cells will release immune modulators at the site of vaccination. These dendritic cells will be mixed with the melanoma antigen-loaded dendritic cells and injected as a vaccine into lymph nodes. Each subject will receive six weekly injections of their own dendritic cells. Safety and toxicity will be closely monitored. In addition, immune responses against melanoma, as well as clinical responses, will be assessed.

Key facts

Study ID

NCT01216436

Run by

Duke University

People needed

2

Starts

2010-01-01

Expected to finish

2013-10-01

Last updated by the study team

2015-05-25

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients with confirmed metastatic melanoma
• Karnofsky performance status greater than or equal to 70%.
• Estimated life expectancy > 6 months.
• Age > 17 years.
• Adequate hematologic function with:
• WBC >= 3000 mm3
• hemoglobin >= 9 mg/dl
• platelets >= 100,000/mm3
• Adequate renal and hepatic function with:
• serum creatinine < 2.5 mg/dl
• bilirubin < 2.0 mg/dl
• AST/SGOT < 70 U/L
• ALT/SGPT < 70 U/L
• Alkaline Phosphatase ≤ 135 U/L
• Ability to understand and provide signed informed consent that fulfills Institutional Review Board guidelines.
• Ability to return to Duke University Medical Center for adequate follow-up as required by this protocol.

You may not qualify if…

• Subjects undergoing concurrent chemotherapy, radiation therapy, or immunotherapy will be excluded.
• The subject has previously irradiated, surgically treated, or newly diagnosed central nervous system (CNS) metastases will be excluded (Pre-enrollment head CT is not required if not indicated by clinical signs or symptoms).
• Subjects with a history of autoimmune disease such as, but not restricted to, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis will be excluded.
• Subjects with serious concurrent chronic or acute illness such as pulmonary (asthma or COPD), cardiac (NYHA class III or IV) or hepatic disease, or other illness considered by the principal investigator to constitute an unwarranted high risk for investigational drug administration will be excluded.
• Subjects with medical or psychological impediment to probable compliance with the protocol will be excluded.
• Subjects with concurrent second malignancy other than melanoma or non-melanoma skin cancer will be excluded. In the event of prior non-melanoma malignancies treated surgically, the subject must be considered NED (no evidence of disease) for a minimum of 3 years prior to enrollment.
• Presence of an active acute or chronic infection, including symptomatic urinary tract infection, HIV (as determined by ELISA and confirmed by Western Blot) or viral hepatitis (as determined by HBsAg and Hepatitis C serology) will lead to subject exclusion.
• Subjects receiving steroid therapy (or other immunosuppressive agents such as azathioprine or cyclosporine A) are excluded on the basis of potential immune suppression.
• Subjects with inadequate peripheral vein access to undergo leukapheresis will be excluded.
• Female subjects with a positive pregnancy test, as well as those who have not previously undergone hysterectomy and/or bilateral oophorectomy and are unwilling to utilize a medically approved form of contraception, from the time of enrollment until 6 weeks after the final immunization, will be excluded.
• Male subjects, not previously surgically sterilized, who are unwilling to use a condom with spermicide during any sexual activity occurring over the entire immunization period and for the 6 weeks that immediately follow the final immunization will be excluded.
• Subjects with a documented history of severe allergic reaction to beta-lactams, eggs or soy products.

Where it is running

• Duke University Medical Center — Durham, North Carolina, United States

Full record on ClinicalTrials.gov

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