Chemotherapy Plus Vaccination to Treat Mantle Cell Lymphoma

Summary

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....

Timeline

Start

2000-06-01

Primary completion

2021-06-09

Completion

2021-06-16

Publications

• Background Pittaluga S, Bijnens L, Teodorovic I, Hagenbeek A, Meerwaldt JH, Somers R, Thomas J, Noordijk EM, De Wolf-Peeters C. Clinical analysis of 670 cases in two trials of the European Organization for the Research and Treatment of Cancer Lymphoma Cooperative Group subtyped according to the Revised European-American Classification of Lymphoid Neoplasms: a comparison with the Working Formulation. Blood. 1996 May 15;87(10):4358-67.
• Background Armitage JO. Management of mantle cell lymphoma. Oncology (Williston Park). 1998 Oct;12(10 Suppl 8):49-55.
• Background Weisenburger DD, Armitage JO. Mantle cell lymphoma-- an entity comes of age. Blood. 1996 Jun 1;87(11):4483-94. No abstract available.
• Results Grant 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.
• Results Neelapu 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.
• Results Roschewski 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.
• Results Wilson WH, Neelapu S, White T, et al: Idiotype Vaccine Following EPOCH-Rituximab Treatment in Untreated Mantle Cell Lymphoma. Pro Am Soc Heme, 2002.
• Results Neelapu S, Wilson WH, Baskar W, et at: Induction of T-cell responses by tumor antigen vaccination in mantle cell lymphoma following rituximab-based treatment. Pro Am Soc Clin Oncol, 2003.
• Results Rosenwald A, Wright G, Wiestner A, Chan WC, Connors JM, Campo E, Gascoyne RD, Grogan TM, Muller-Hermelink HK, Smeland EB, Chiorazzi M, Giltnane JM, Hurt EM, Zhao H, Averett L, Henrickson S, Yang L, Powell J, Wilson WH, Jaffe ES, Simon R, Klausner RD, Montserrat E, Bosch F, Greiner TC, Weisenburger DD, Sanger WG, Dave BJ, Lynch JC, Vose J, Armitage JO, Fisher RI, Miller TP, LeBlanc M, Ott G, Kvaloy S, Holte H, Delabie J, Staudt LM. The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma. Cancer Cell. 2003 Feb;3(2):185-97. doi: 10.1016/s1535-6108(03)00028-x.
• Results Wilson WH, Neelapu S, Rosenwald A, et al: Idiotype Vaccine and Dose-Adjusted EPOCH-Rituximab Treatment in Untreated Mantle Cell Lymphoma: Preliminary Report on Clinical Outcome and Analysis of Immune Response. 2003, Blood 102 (11) #358.
• Results Fu K, Weisenburger DD, Greiner TC, Dave S, Wright G, Rosenwald A, Chiorazzi M, Iqbal J, Gesk S, Siebert R, De Jong D, Jaffe ES, Wilson WH, Delabie J, Ott G, Dave BJ, Sanger WG, Smith LM, Rimsza L, Braziel RM, Muller-Hermelink HK, Campo E, Gascoyne RD, Staudt LM, Chan WC; Lymphoma/Leukemia Molecular Profiling Project. Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling. Blood. 2005 Dec 15;106(13):4315-21. doi: 10.1182/blood-2005-04-1753. Epub 2005 Aug 25.
• Results Wiestner A, Tehrani M, Chiorazzi M, Wright G, Gibellini F, Nakayama K, Liu H, Rosenwald A, Muller-Hermelink HK, Ott G, Chan WC, Greiner TC, Weisenburger DD, Vose J, Armitage JO, Gascoyne RD, Connors JM, Campo E, Montserrat E, Bosch F, Smeland EB, Kvaloy S, Holte H, Delabie J, Fisher RI, Grogan TM, Miller TP, Wilson WH, Jaffe ES, Staudt LM. Point mutations and genomic deletions in CCND1 create stable truncated cyclin D1 mRNAs that are associated with increased proliferation rate and shorter survival. Blood. 2007 Jun 1;109(11):4599-606. doi: 10.1182/blood-2006-08-039859. Epub 2007 Feb 13.
• Results Dunleavy K, Neelapu SS, Kwak LW, Grant C, Santos CF, Popa M, White T, Miller B, Jaffe ES, Steinberg SM and Wilson WH. Association of idiotype vaccine-induced T-cell response with improved survival and time-to-next treatment (TTNT) in untreated mantle cell lymphoma (MCL). Journal of Clinical Oncology, 2012 ASCO Annual Meeting Proceedings (Post-Meeting Edition).Vol 30, No 15_suppl (May 20 Supplement), 2012: 2528.
• Lai C, Cole DE, Steinberg SM, Lucas N, Dombi E, Melani C, Roschewski M, Balis F, Widemann BC, Wilson WH. Doxorubicin pharmacokinetics and toxicity in patients with aggressive lymphoma and hepatic impairment. Blood Adv. 2023 Feb 28;7(4):529-532. doi: 10.1182/bloodadvances.2022007431.

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