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About Non-Hodgkin's Lymphoma and Accentia's Biovaxid Vaccine
What is Non-Hodgkin's Lymphoma (NHL)?
Non-Hodgkin's Lymphoma (NHL) is a cancer that starts in the lymphatic system. Most people are familiar with lymph nodes; however the lymphatic system is a complex network of organs, ducts and nodes that interact with the blood circulatory system. The system of lymphatic vessels run throughout the body and connect lymph organs (bone marrow, spleen, thymus and lymph nodes (glands)). Circulating through the lymph system are white blood cells called lymphocytes. The lymphocytes (white blood cells) are an important part of the body's immune system to fight infection and disease. The lymphocytes are further classified as B-cell and T-cell lymphocytes. Both B -cells and T- cells fight infection but in different ways.
Although all lymphomas (cancer of the lymphatic system) start in the lymphatic system, they are broadly classified into two major groups, B-cell lymphoma and T-cell lymphoma. B-cell lymphoma develops from an abnormal B-cell and T-cell lymphoma develops from an abnormal T-cell. B-cell Non-Hodgkin's Lymphoma is much more common than T-cell lymphoma. In fact about 85% of Non-Hodgkin's Lymphomas are B-cell. These abnormal cells multiply uncontrollably to form tumors and spread through the lymphatic system. These two major groups, B-cell and T-cell, are further classified into over 20 subtypes depending on the clinical symptoms, location of the lymphoma and what the cells look like under the microscope. The subtypes of lymphomas will progress differently, some will be very fast growing tumors (aggressive) and other will be slow growing tumors (which are called 'indolent').
The treatment of Non-Hodgkin's Lymphoma depends on the subtype (i.e. indolent follicular) and the stage (how long the person has had the cancer). To diagnose Non-Hodgkin's Lymphoma, the physician will take a biopsy of the tissue in the site thought to be cancerous. From this biopsy, the physician will determine if it is cancerous and if so the type. To determine the stage of the cancer, the physician will collect information from physical exams, blood tests, x-rays, CAT scans or ultrasounds of various organs and tissues. In some cases the physician may also collect biopsies of the bone marrow and lymph nodes.
What are the typical symptoms of Non-Hodgkin's Lymphoma?
The first and most common sign is often a painless swelling of the lymph nodes either in the neck, arm pit or groin. However lymph nodes can be enlarged for reasons other than cancer. Other symptoms include night sweats, weight loss, unexplained high temperatures and fatigue. If the disease has spread from the lymph nodes to other organs, other symptoms will appear. For example if the cancer has spread to the stomach, the patient will experience nausea, vomiting or stomach pain. Whereas if the cancer has spread to the brain, symptoms might include headache, vision changes or seizures. These symptoms could be signs of conditions other than cancer. It is important to realize that only your physician can make a diagnosis.
How common is Non-Hodgkin's Lymphoma?
Non-Hodgkin's Lymphoma is the sixth most common cancer in the USA. Although people of any age can develop NHL, the risk increases with age. More than half the cases are in people age 60 years and older. It is estimated that 56,000 new cases of NHL were diagnosed in the USA in 2003.
What causes Non-Hodgkin's Lymphoma?
There is no known cause of Non-Hodgkin's Lymphoma. It has been linked to pesticides, hair dyes, AIDS and immune suppressing therapies, although these have never been proven.
What are the treatment options for Non-Hodgkin's Lymphoma?
The treatment of NHL will depend on the type and stage. Some types of NHL are curable (disappearance of all evidence of disease) with existing therapies which include chemotherapy, radiation and monoclonal antibodies (antibody is made from a single clone of cells). However some types of Non-Hodgkin's Lymphoma are not curable with existing therapies and are eventually fatal. For these types of NHL, enrollment in a clinical trial studying new agents is an option many physicians and patients consider.
What new therapies are being studied in NHL?
Several approaches are being studied which include 'therapeutic' vaccines (a type of immunotherapy), antibodies and gene expression profiling.
What is a cancer vaccine?
Cancer vaccines are very different from the vaccines that are now given to prevent the flu and small pox. Cancer vaccines are given to treat the cancer after it has been diagnosed (i.e. given therapeutically). Cancer vaccines are also individualized for each patient and are called personalized or patient specific (also call 'autologous') vaccines. In order to make these personalized vaccines, the physician takes a biopsy (a sample or part of the cancerous tumor) before the patient undergoes chemotherapy. The biopsy is then sent to the lab where the cells in the biopsy undergo a very specialized process to create a vaccine unique to the individual patient's cancer. This highly technical process takes around six months to create a vaccine specific to the individual patient.
Does the cancer vaccine work in both B-cell and T-cell lymphomas?
The BIOVAXID™ vaccine was originally developed and tested in B-cell lymphomas. The B-cell carries a unique special marker protein on its surface. It is this special marker on the B-cell that the vaccine is created to recognize. The vaccine has shown great promise in the treatment of B-cell lymphoma.
Why does the vaccine have to be individualized for each person?
Each person's cells are different and unique to the individual. As previously mentioned, each B-cell has a unique marker on the cell surface. The marker expressed by the B cell is a protein and this protein 'idiotype' is specific to the individual cell. The normal B-cells in the individual are different from one another. However, B-cell lymphoma occurs when one B-cell transforms' and becomes cancerous. This cancerous B-cell then 'clones' itself and each of these new 'clones' bears the protein idiotype that was specific to the original malignant cell. So each person's cancerous B-cells are unique to that person, therefore each vaccine has to be created to replicate the marker of the original malignant cell and its cancerous clones.
How is the BIOVAXID™ vaccine made for each patient?
The individual patient's cancerous B-cell is identified from the biopsy sent to Accentia BioPharmaceuticals manufacturing facility, Biovest. The 'special marker molecule' (called idiotype) on the cancerous B-cell is identified through a special process. Biovest takes this cell idiotype and turns it around to create a tumor-specific marker. The vaccine (BIOVAXID™) is then created by a molecular process from the individuals cells with this tumor-specific marker. The cancerous cells were not recognized by the individual's immune system as foreign or transformed because this marker closely resembled a normal cell. This allowed the cancer to grow. The lab takes the cell with the tumor specific marker and links it to a protein molecule called keyhole limpet hemocyanin ((KLH) By linking it to KLH, it makes the tumor's specific marker easily recognized by the individuals own immune system. This highly technical and precise process undergoes several quality checks to make sure all the 'points' on the special marker molecule or idiotype have been found and that a native, unaltered vaccine is created.
How does the BIOVAXID™ vaccine work?
As stated earlier, the lymphatic system is part of the immune system. Circulating through the lymphatic system are lymphocytes (white blood cells). These white blood cells are made up of B-cells and T-cells. The job of the B-cell is to circulate in the lymphatic system and to inactivate any foreign substance (a substance recognized as not belonging in the body, i.e. infection). The B-cell inactivates the 'foreign substance' (called antigen) by secreting an antibody onto the foreign substance. These antibodies secreted by the B-cell bind to and inactivate the foreign substance. Now this foreign substance is attached to a cell. This is important because T-cell can only recognize foreign substance attached to a cell. The job of the T-cell is to recognize this foreign substance and to kill this abnormal cell.
The vaccine is made up of the individual cancer cell 'idiotype' that has been made highly recognizable by the body by the addition of KLH. Now the body is able to recognize the cancerous B-cell as a foreign substance. The vaccine is administered with an immune booster to increase the immune response. The body's own immune system kicks into high gear and the normal B-cell recognize the cancerous B-cell and secrete an antibody to it's surface and binds to it making it 'inactive'. The T-cell then recognizes the foreign substance now attached to a cell and kills' the cancerous B-cell . Additionally, the body has stored a memory for what this cancer cell looks like and will start the immune response of B-cell and T-cell attacking it when or if it reappears.
Will the vaccine work in all patients with Non-Hodgkin's Lymphoma?
The vaccine is being studied in only follicular Non-Hodgkin's Lymphoma (slow growing B-cell lymphoma). Additionally it is currently being studied only in newly diagnosed patients.
When you say it is being studied, does that mean it is not yet approved?
The vaccine is currently in the final investigational research stage of clinical trials. It is not currently approved. To receive the vaccine, newly diagnosed patients with follicular Non-Hodgkin's Lymphoma must enroll in the phase III trial.
What is a Phase III trial?
Before the FDA will approve a drug, the sponsoring company must conduct several clinical studies. The studies are done in phases to determine what the side effects of the drug are and how effective it is in treating the disease. The earliest studies (pre-clinical, meaning in the lab before they are given to anyone) are to determine if the drug works in the way it was thought to work. Pre-clinical toxicology will look at the safety of the drug before it is given to anyone. Phase I trials evaluate the safety of the new therapy in a small number of human subjects. Phase II trials investigate the new therapy's safety in a larger group of humans, and determine the most effective dose and duration. Phase III trials are the last part of the clinical development process. In these studies, a large number of patients are treated with the dose regimen that was identified in the earlier trials in order to prove that the new medication is both safe and effective for its intended therapy. When the clinical trials are complete, these data will be submitted to the FDA for their review. When FDA has completed their review and makes a determination that safety and efficacy have been satisfactorily proven, they approve the new drug for commercial use.
Why is it only for newly diagnosed patients?
The biopsy needed to make the vaccine must be taken from a cancerous site that has not yet undergone any treatment.
What about patients that relapsed after a few years but were previously treated with chemotherapy or radiation?
BIOVAXID is not currently being studied in previously treated patients with Non-Hodgkin's who relapse. However some new therapies are being studied. For information on those clinical trials you should contact the National Cancer Institute at 1-888-NCI-1937 or visit the following web sites for more information:
Will I still have to have chemotherapy prior to the vaccine therapy?
Yes. One course of chemotherapy is given to reduce the tumor burden (amount of cancerous cells). Chemotherapy is generally given monthly over a course of 6 months. In the BIOVAXID trial, patients are then given a 'rest' period of 6 to 12 months before vaccine therapy is given. The rest period is to allow the immune system to rebound from the chemotherapy.
What is the course of treatment with BIOVAXID™?
BIOVAXID is given as a monthly subcutaneous injection (injection just under the skin) after the rest period in months 1, 2, 3, 4 and a fifth booster injection in month 6. It is administered with an immune booster called GM-CSF. GM-CSF is given on days 1-4 in months 1, 2, 3, 4 and 6.
If the chemotherapy works and I am in complete remission afterwards, why would I want to enroll in the phase III trial?
Unfortunately indolent (slow growing) follicular Non-Hodgkin's Lymphoma is not considered curable with current treatments.
What have the results been with the vaccine?
The first clinical trials were conducted at Stanford in 1988 and involved 41 patients with indolent (slow growing) form of B-cell lymphoma. These patients were given chemotherapy which they had either a complete response (no detectable tumor) or a partial response (reduction in tumor burden of at least 50%). Of the 41 patients, 32 were in remission following their first course of therapy. The remaining 9 patients achieved remission following two or three courses of chemotherapy. The vaccine was given to patients in remission and positive immune response was seen in 20 of the 41 patients given the vaccine. This includes 14 of the 32 patients who were in complete remission following the first course of chemotherapy. The patients were followed and the long term follow up was published in 'Blood' in May 1997. The long term follow-up results showed that the patients who had a positive immune response had a median time to relapse of 7.9 years (time between remission and reappearance of detectable cancer) compared to 1.3 years in those who did not have a positive immune response. In 1997 when the study was published, the median long term survival of all 41 patients was analyzed. The Stanford physician investigators concluded that the long term survival in the vaccination patients was significantly longer than those patients with identical diseases that had not received the vaccination.
The second trial (phase II) was conducted by the National Cancer Institute (NCI) and published in 'Nature Medicine' in October 1999. In this trial, 20 patients were enrolled who had achieved complete remission after chemotherapy (however using a very sensitive DNA-based test, 11 of the 20 considered in complete remission were shown to still have cancer cells in their blood). Of these 20 patients, 95% had significant positive immune response to the vaccine. This included 73% (8 of the 11) who had been determined to still have cancer cells in the blood after chemotherapy. At the end of the study (23 to 53 months), 90% of patients remained in complete remission. Follow up after seven years, median time to relapse had exceeded 7 years in the group who had received the vaccine.
What have the side effects been?
Most patients receiving the vaccine have had redness or swelling and some pain at the injection site. These side effects generally only occur with each injection and disappear within a few days.
As with any medication, there is a possibility of an allergic reaction, in this case to KLH (immune stimulant). It is unlikely that an allergic reaction would be related to the vaccine as it made from the patient own cells.
Where can I learn more about becoming a participant in the BIOVAXID™clinical trial?
Click here for site locations, physician name and contact information
Where can I find out more information about Non-Hodgkin's Lymphoma?
There are some excellent organizations dedicated to providing comprehensive, up-to-date information for patients and their families on the disease information, current treatments, research, clinical trials and support services. Below are the organizations and their web sites.
- Lymphoma Research Foundation
- » www.lymphoma.org
- The Leukemia and Lymphoma Society
- » www.leukemia-lymphoma.org
- Lymphoma Focus
- » www.lymphomafocus.org
- American Cancer Society
- » www.cancer.org
- National Cancer Institute
- » www.cancer.gov
- Cancer Vaccine Fact Sheet developed by the National Cancer Institute
- » www.cancer.gov/newscenter/pressreleases/cancervaccines
- Patients Against Lymphoma
- » http://www.lymphomation.org
Where can I go to find out about all the clinical trials ongoing for Non-Hodgkin's Lymphoma?
The sites below list most of the clinical trials currently enrolling patients for Non-Hodgkin's Lymphoma. (Click in the link below)
