Chemotherapy Plus Vaccination to Treat Mantle Cell Lymphoma

This study will evaluate the safety and effectiveness of an experimental cancer vaccine for mantle cell lymphoma a form of cancer of the white blood cells called lymphocytes. Although standard treatments for lymphoma may achieve disease remission, none provides a cure. Patients with mantle cell lymphoma 18 years and older who have not been treated previously with chemotherapy may participate in this study. Candidates will be screened for eligibility with a medical history and physical examination. Other tests that may be required include blood and urine tests; lung function studies; imaging tests such as magnetic resonance imaging, computed tomography and X-rays; and biopsy (surgical removal of a small tissue sample) of tumor, bone marrow, or other tissue. Patients enrolled in the study will begin treatment with chemotherapy designed to reduce disease to a minimum that is, to achieve remission or shrink the tumor as much as possible. Chemotherapy will be administered on an outpatient basis over a period of around 12 to 18 weeks in 3-week cycles as follows: prednisone by mouth on days 1 through 5; etoposide, doxorubicin and vincristine intravenously through (a vein) on days 1 through 5; and cyclophosphamide intravenously on day 5. Starting day 6, patients receive no chemotherapy for 16 days. In addition, an antibody called rituximab, which attaches to lymphoma cells and may increase the effectiveness of the chemotherapy, will be given on day 1 of the cycle. Patients will also receive a protein called granulocyte colony-stimulating factor (G-CSF) starting day 6 of the cycle and continuing until the white blood cell count recovers or until day 19. G-CSF is naturally produced by bone marrow and may boost the immune system. The chemotherapy drugs and rituximab are infused through a vein by means of a lightweight portable pump, which patients are taught how to use. Patients are also how taught how to give themselves G-CSF injections under the skin, similar to insulin injections. The first vaccination will be given at least 3 months after chemotherapy ends and will be repeated every 4 weeks for a maximum of 5 vaccinations. The vaccinations will be given in the clinic. Patients will also receive daily injections of granulocyte-macrophage colony-stimulating factor (GM-CSF), a growth factor naturally produced by bone marrow that can boost the immune system. These injections will be given the day of the vaccination and for the next 3 days. When vaccine therapy is completed, patients who were treated successfully will be followed with periodic clinic visits for follow-up examinations and tests. Patients in whom the lymphoma did not disappear entirely or who have a recurrence of disease will be advised of further treatment possibilities....

Sex

All

Minimum age

18 Years

* INCLUSION CRITERIA:

Tissue diagnosis of mantle cell lymphoma (confirmed in Laboratory of Pathology). Blastic cell variant will be eligible.

Age greater than or equal to 18.

Previously untreated with cytotoxic chemotherapy. Patients may have received local radiation or a short course of steroids for control of symptoms.

All stages of disease.

Lymph node of greater than or equal to 2 cm accessible for biopsy/harvest or greater than 1000/microliters of circulating tumor cells in the blood.

Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 3.

Adequate major organ function (serum creatinine 1.5 mg/dl or creatinine clearance greater than 60 ml/min; bilirubin less than 2 mg/dl (total) except less than 5 mg/dl in patients with Gilbert's syndrome as defined by greater than 80% unconjugated; absolute neutrophil count (ANC) greater than 1000 and platelets greater than 100,000) unless impairment due to organ involvement by lymphoma.

No active symptomatic ischemic heart disease, myocardial infarction or congestive heart failure within the past year. If multigated acquisition (MUGA) scan is obtained, the left ventricular ejection fraction (LVEF) should exceed 40%.

Ability to give informed consent.

EXCLUSION CRITERIA:

Antibodies to human immunodeficiency virus (HIV) or presence of hepatitis B surface antigen.

Pregnant or lactating.

Prior malignancy in past 5 years except squamous or basal cell carcinoma or curatively treated in situ of the cervix.

Involvement of central nervous system by lymphoma.

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• RESULTGrant C, Neelapu SS, MD2, Kwak LW, Dunleavy K, White T, Miller BW, Jaffe ES, Steinberg SM, Healey Bird B, MB, Wilson WH. Eleven-Year Follow-up of Idiotype Vaccine and DA-EPOCH-Rituximab in Untreated Mantle Cell Lymphoma: Correlation of Survival with Idiotype Immune Response. Blood (ASH Annual Meeting Abstracts) 2011 118: Abstract 2707.
• RESULTNeelapu SS, Kwak LW, Kobrin CB, Reynolds CW, Janik JE, Dunleavy K, White T, Harvey L, Pennington R, Stetler-Stevenson M, Jaffe ES, Steinberg SM, Gress R, Hakim F, Wilson WH. Vaccine-induced tumor-specific immunity despite severe B-cell depletion in mantle cell lymphoma. Nat Med. 2005 Sep;11(9):986-91. doi: 10.1038/nm1290. Epub 2005 Aug 21. PMID 16116429
• RESULTRoschewski M, Dunleavy K, Neelapu SS, Pittaluga S, Melani CJ, Jaffe ES, Shovlin M, Crossley B, Kong K, Jacob A, Kwak L, Wilson WH. Quantitative Baseline Circulating Tumor DNA Levels Correlate with GM-CSF Response to Idiotype Vaccine in Untreated Mantle Cell Lymphoma (ASH Annual Meeting Abstracts). Blood. 2016;128:2943-2943.
• RESULTWilson WH, Neelapu S, White T, et al: Idiotype Vaccine Following EPOCH-Rituximab Treatment in Untreated Mantle Cell Lymphoma. Pro Am Soc Heme, 2002.