R-Chemo Study FAQs

1. What is this study evaluating?


This study is evaluating the use of an experimental treatment known as MyVax® personalized active immunotherapy in patients with follicular non-Hodgkin’s lymphoma (fNHL) receiving rituximab in combination with cyclophosphamide, vincristine, and prednisone (CVP) or cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) chemotherapy (R-Chemo). Twenty-four doses of MyVax® personalized active immunotherapy (1 every 4 weeks) will be given to each patient enrolled in the study, starting 26 weeks after completion of R-Chemo.

2. What is MyVax® personalized active immunotherapy?

MyVax® personalized active immunotherapy uses a person’s own immune system (thus, the term immunotherapy) in an attempt to combat B-cell malignancies. MyVax® personalized active immunotherapy is called personalized immunotherapy because it is developed from an idiotype or Id protein, which is identified from the patient’s tumor cells and is unique to that patient’s tumor cells. In fact, the Id can be thought of as a tumor cell “fingerprint”. MyVax® personalized active immunotherapy is different from currently available therapies in that it is made individually and specifically for each patient. Since it has been custom-designed to work with each patient’s immune system and to target each patient’s tumor cells, healthy cells within the patient’s body should not be affected.

MyVax® personalized active immunotherapy is composed of (1) the patient- and tumor-specific idiotype (Id) protein, and (2) a second protein called keyhole limpet hemocyanin (KLH). KLH comes from a giant sea mollusk that lives off the coast of California. This protein is highly immunogenic, meaning that when it is put into the body, the immune system responds strongly to it—and to anything attached to it. In addition, an adjuvant (a substance that enhances the immune response) is administered along with MyVax® personalized active immunotherapy. This adjuvant is called granulocyte-macrophage colony-stimulating factor (GM-CSF).

Patient- and tumor-specific personalized immunotherapy such as MyVax® personalized active immunotherapy may also be referred to as active idiotype immunotherapy, idiotype (Id) vaccines, or therapeutic idiotype vaccines. These are simply different names for the same therapeutic approach.

3. What is MyVax® personalized active immunotherapy designed to do?

In patients with B-cell malignancies, it is hoped that MyVax® personalized active immunotherapy will improve the response and/or extend remissions after initial standard treatments such as chemotherapy administered with or without monoclonal antibody therapy or monoclonal antibody therapy alone. At this time, it is not known whether MyVax® personalized active immunotherapy will be effective in treating these malignancies. However, the effect of this active immunotherapy on the duration of remission is one of the questions being asked in clinical studies.

4. What is the rationale behind this particular study?

Using rituximab or rituximab-containing regimens (eg, R-CVP, R-CHOP) to treat follicular non-Hodgkin's lymphoma targets and eliminates both malignant and healthy B-cells which display the CD20 antigen. After receiving rituximab, it can take 6 to 12 months for a patient's B-cells to return to pre-treatment levels and normal function. It is thought that the longer remissions seen with R-Chemo should allow enough time for the patient’s B-cells to recover. This is important because it is thought that MyVax® personalized active immunotherapy uses both the humoral (B-cell) and cellular (T-cell) arms of the immune system in an attempt to combat B-cell malignancies.

5. How is MyVax® personalized active immunotherapy manufactured?

The first step in the manufacturing of MyVax® personalized active immunotherapy is the collection of a tumor sample from the patient. From that sample, the unique genetic material associated with the specific idiotype (Id) that the person’s cancer is expressing (producing) is identified and isolated. This genetic material is used to produce a recombinant, or genetically engineered, version of the Id protein, which is grown in the laboratory, purified, and combined with KLH.

In a small number of cases, it may not be possible to produce a personalized immunotherapy for a specific patient due to the biology of his/her cancer cells (ie, the cancer cells may not express an Id protein or may not produce enough of the Id protein).

6. Do patients have to undergo a second biopsy to obtain the tumor sample from which MyVax® personalized active immunotherapy is manufactured, or can previously frozen diagnostic tissue be submitted for manufacturing?

A patient does not have to undergo a second biopsy if adequate frozen diagnostic tissue from a biopsy done within six months of study enrollment is available.

7. This study is described as being an “open label” study. What does that mean?

“Open label” means that the researchers and patients participating in the study know what treatment is being received (every patient enrolled in this study will be receiving MyVax® personalized active immunotherapy). This is in contrast to “blinded” studies in which the patients and researchers do not know what treatment patients are receiving. Blinding is common in studies where not all patients are receiving the study drug, i.e., where some patients are receiving a control agent (also known as a placebo) along with standard treatment. In cancer clinical trials involving more than one treatment arm, it is unethical to treat patients with anything less than the standard of care for that disease..

8. This study is measuring “humoral anti-Id and anti-KLH immune responses.” What does that mean?

A “humoral immune response” is the development of antibodies made by the immune system’s B cells. “Humoral anti-Id and anti-KLH immune responses” are measurements in the blood of the specific antibodies the immune system has made against a patient’s unique idiotype (Id) protein and the KLH protein.

9. This study is also measuring “progression-free survival.” What is that?

“Progression-free survival” is the time period during which a patient remains alive and his or her disease has not become worse (progressed). Progression Free Survival is often used to determine whether or not a new treatment is effective.

10. What are the results of previous studies looking at personalized active immunotherapy?

Personalized active immunotherapy has been studied in patients since the mid-1980s, and appears to be safe and well tolerated. To date, hundreds of personalized active immunotherapies have been manufactured for use in clinical studies.
Initial results associated with personalized active immunotherapy in patients with NHL have been as follows:

  • In early small studies, personalized active immunotherapy has shown anti-tumor activity, with long-term durable remissions (median of 42+ months from the completion of chemotherapy) observed in some patients1,2
  • In a more recent Phase 2 study conducted by Genitope, 9 of 21 patients remained in remission for between 57 and 78 months as measured from the end of chemotherapy.3 To date, these 9 patients have not required any additional lymphoma treatments


11. Who is eligible for this study?

To be eligible for this study, a patient must meet ALL of the following criteria:

  • Provide written informed consent. Written informed consent refers to the reading and signing of a document that clearly spells out what is involved in the clinical study (including its purpose, duration, required procedures, and potential risks and benefits). By signing the written informed consent, the patient agrees to participate in the study. Even after signing the written informed consent, the patient may withdraw from the study at any time.\
  • Diagnosis of follicular NHL that is:
    • Grade I, II, or III disease (grade is a measure of the speed at which the disease is growing)
    • Stage III or IV disease requiring treatment (stage refers to where in the body the disease has spread; whether or not a particular patient requires treatment will be determined by his/her physician) No previous anti-lymphoma treatments (including biologic, steroidal, cytotoxic, or radiation therapies)
  • Be able to receive R-Chemo. Patients will not receive maintenance rituximab during this study.
  • Be 18 years of age or older
  • Be willing and able to provide a tumor sample adequate for MyVax® personalized active immunotherapy manufacturing (e.g., there must be tumor tissue that is accessible for biopsy and the patient must be willing to undergo the biopsy procedure if no adequate biopsy is available).
  • Have at least one bi-dimensionally measurable lesion ≥2 cm by CT scan (for baseline purposes) after the tumor sample has been obtained


12. Can patients who have been “watching and waiting” participate in this study, or is it only open to newly diagnosed patients?

As long as the eligibility criteria are met and the patient has not received any treatment for his/her lymphoma, patients who are watching and waiting may qualify for this study.

13. What is the time commitment for patients participating in this study?

The total time a given patient will be involved in this study is approximately 4 years.

Once a patient is accepted into the study, a tumor biopsy is taken and sent to the study sponsor for manufacturing of that patient’s MyVax® personalized active immunotherapy. After the physician at the study site is notified that personalized immunotherapy can be manufactured for the patient, the patient will begin the required 6–8 cycles of rituximab combined with chemotherapy over 18–24 weeks, followed by a 26-week (6-month) rest period, during which the immune system recovers from R-Chemo. The patient will be evaluated 4 weeks after completing their initial therapy, and again approximately 6 weeks prior to starting treatment with MyVax® personalized active immunotherapy, to ensure that he/she still qualifies to continue in the study.

During the 92 weeks of treatment with MyVax® personalized active immunotherapy, the patient is seen every 4 weeks. The patient will also be seen for study visits at 6 weeks, 3 months, 9 months, and 15 months after treatment with MyVax® personalized active immunotherapy has been completed.

After finishing the study, patients or their doctors will be contacted every 6 months in order for the study sponsor to collect information about subsequent anti-lymphoma therapy and survival.

14. Where is the study being conducted?

This study is being conducted at multiple sites throughout the United States. For a current listing of participating centers, call 1.866.GENITOP (1.866.436.4867) or visit www.genitope.com.

15. Can the biopsy to obtain the tumor sample from which MyVax® personalized active immunotherapy is manufactured be done by the patient’s treating physician, or does it have to be done at the study site?

The physician at the study site determines where the biopsy will be performed. It is strongly recommended that the biopsy be performed at the study site.

16. Can the patient’s treating physician administer the R-Chemo treatments?

Yes, initial treatment with R-Chemo may be administered locally by the patient’s treating physician.

17. What is the cost to participate in this study? What costs are covered by medical insurance? Is there assistance to help with these costs?

MyVax® personalized active immunotherapy and GM-CSF are provided at no cost to patients participating in this study. However, since some of the other study-related visits and procedures are considered standard of care, these medical costs will be billed to the patient’s insurance. Some study sites provide study participants with reimbursement for travel-related costs, so study participants may want to check with the study site to see if reimbursement is available.

Patient advocacy organizations such as the Patient Advocate Foundation (www.patientadvocate.org) and the Leukemia-Lymphoma Society (www.lls.org) have programs to assist lymphoma patients with insurance co-payments. The Lymphoma Research Foundation (www.lymphoma.org) and the Leukemia-Lymphoma Society (www.lls.org) also have patient financial aid programs to assist patients with other treatment-related costs. Visit their Web sites for more information.

18. What happens if a patient participating in this study does not respond to R-Chemo as initial therapy?

Patients enrolled in this study must achieve at least a partial response (at least a 50% reduction in tumor mass) to initial therapy with R-Chemo or they will no longer be eligible to participate in this study.

19. Why is a 6-month rest period required after initial therapy with R-Chemo and before MyVax® personalized active immunotherapy is administered?

The 6-month rest period is required to give the immune system time to recover from the impact of R-Chemo, especially the B cells.

20. What happens if a patient’s lymphoma progresses (gets worse) after initial therapy with R-Chemo?

If a patient’s cancer progresses to the point where additional therapy is required to control the disease, that patient will no longer be eligible to participate in this study and will not be able to receive MyVax® personalized active immunotherapy.

21. How is MyVax® personalized active immunotherapy administered?

MyVax® personalized active immunotherapy is given as a series of injections just under the skin (subcutaneously) via a small needle. Each MyVax® personalized active immunotherapy injection is given along with an injection of GM-CSF. This is followed by a 3-day series of once-daily GM-CSF injections for the first 12 doses of MyVax® personalized active immunotherapy. This 3-day series of GM-CSF can be self-administered at home. All injections of Id-KLH are administered at the study site.

22. What physical reaction should patients expect as a result of the treatment?

Adverse events that patients receiving MyVax® personalized active immunotherapy have reported include injection-site reactions, such as redness, swelling, bruising, itching, soreness, and/or pain at the site of the injection. Some patients also experienced flu-like symptoms, including fever, chills, nausea, and muscle soreness. These adverse events generally occur in the first few days after the injection, but they may last longer.

Side effects associated with the adjuvant (GM-CSF) include fever, bone or joint pain, flu-like symptoms (nausea, headache, tiredness), heartburn, and mild skin reactions at the injection site. More information about GM-CSF side effects can be found at www.leukine.com.

As with any medication, there is a possibility of allergic reactions with MyVax® personalized active immunotherapy. Allergic reactions have been seen in only a small number of patients, and patients are monitored closely after each injection for signs of such reactions. There are effective medications available to counteract allergic reactions, should they be required.

23. Is there a risk of death, secondary cancers, or autoimmune disorders associated with the treatment?

In studies in which MyVax® personalized active immunotherapy has been used to treat patients with NHL, there have been no reports of treatment-related deaths to date. There have been a few reports of new cancers or autoimmune disorders, but it is difficult to determine if these were related to the use of MyVax® personalized active immunotherapy because often these patients also received other medications, such as chemotherapy. Monitoring for these events in patients receiving MyVax® personalized active immunotherapy is ongoing, and these events will also be monitored in this study.

24. How will patients be monitored for response to treatment? How often will they be monitored?

Patients will be monitored with CT scans, blood tests, bone marrow biopsies, and physical examinations by the study doctor to determine response to treatment with rituximab-chemotherapy and MyVax® personalized active immunotherapy. Blood tests will also be done periodically to assess for adverse events that the patient may experience due to treatment during the study.

25. How many patients will be treated in this study?

It is anticipated that 100 patients will receive MyVax® personalized active immunotherapy in this study.

26. Will the results of this study be published?

Yes, study results will be published once the study is completed.

References

1. Hsu FJ, Caspar CB, Czerwinski D, et al. Tumor-specific idiotype vaccines in the treatment of patients with B-cell lymphoma—long-term results of a clinical trial. Blood. 1997;89:3129-3135.
2. Bendandi M, Gocke CD, Kobrin CB, et al. Complete molecular remission induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma. Nat Med. 1999;5:1171-1177.
3. Timmerman J, Vose J, Levy R, et al. Long-term follow-up of patients treated in a phase 2 trial with MyVax® personalized immunotherapy (recombinant Id-KLH plus GM-CSF) after chemotherapy as initial treatment for follicular non-Hodgkin’s lymphoma (NHL). Presented at: 47th Annual Meeting and Exposition of the American Society of Hematology; December 10-13, 2005; Atlanta, Ga. Poster 2348.