Non Hodgkin Lymphoma Clinical Trial
Vorinostat, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma
Summary
This phase I/II trial is studying the side effects and best dose of vorinostat when given together with rituximab and combination chemotherapy and to see how well it works in treating patients with newly diagnosed stage II, stage III, or stage IV diffuse large B-cell lymphoma. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Monoclonal antibodies, such as rituximab, can block cancer cell growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cell-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving vorinostat together with rituximab and combination chemotherapy may kill more cancer cells.
Full Description
PRIMARY OBJECTIVES:
I. To find a safe dose of vorinostat to be used in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone) (vorinostat-R-CHOP). (Phase I) II. To estimate the 2-year progression-free survival (PFS) rate in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) treated with vorinostat and R-CHOP therapy (vorinostat-R-CHOP). (Phase II) III. To estimate the response rate (complete and partial) and 2-year overall survival rate. (Phase II) IV. To evaluate the toxicity of vorinostat-R-CHOP in patients with newly diagnosed DLBCL. (Phase II) V. To assess whether pre-treatment acetylation status of histones, expression of major histocompatibility complex (MHC) class II genes, and/or percentage of cluster of differentiation (CD)8+ tumor infiltrating lymphocytes correlate with progression-free survival. (Phase II) VI. To explore whether treatment with vorinostat-R-CHOP increases histone acetylation, alters expression of MHC class II proteins, or alters percentage of T-cell subsets (CD8+, CD4+, forkhead box P3 [FOXP3]+) or infiltrating macrophages. (Phase II) VII. To explore whether histone acetylation status of tumor tissues correlates with MHC class II expression of peripheral blood B cells and lymphocyte subsets. (Phase II) VIII. To explore whether the change in systemic levels of immune cytokines with vorinostat-R-CHOP correlates with lymphoma symptoms, response, progression-free or overall survival. (Phase II)
OUTLINE: This is a phase I, dose escalation study of vorinostat followed by a phase II study.
Patients receive vorinostat orally (PO) once daily on days 1-5 or 1-9 (according to dose level), rituximab intravenously (IV), cyclophosphamide IV over 30-60 minutes, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 3. Patients also receive prednisone PO once daily on days 3-7. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 6 months for 2 years, and then annually for 3 years.
Eligibility Criteria
Inclusion Criteria:
Patients must have biopsy proven, newly diagnosed DLBCL with stage II bulky, stage III or stage IV disease, with an International Prognostic Index (IPI) or revised (R)-IPI score greater than 0; a report providing confirmation of CD20 expression must be submitted
Adequate sections from the original diagnostic specimen must be available for submission for review by the Southwest Oncology Group (SWOG) Lymphoma Pathology Laboratory; an adequate biopsy requires sufficient tissue to establish the architecture and World Health Organization (WHO) histologic subtype with certainty; fine needle aspiration or cytology is not adequate
Patients must be offered the opportunity to consent to the correlative science studies; patients are encouraged to submit specimens for correlative studies; however, specimen submission is not a requirement for participation in the study
Patients must have measurable disease; measurable disease must be determined by computed tomography (CT) scan of chest, abdomen and pelvis performed within 28 days prior to registration; positron emission tomography (PET)/CT may be substituted for CT scan only if CT scan is of diagnostic quality and is contrast enhanced
Patients must have a unilateral bone marrow aspirate and biopsy for staging performed within 42 days prior to registration
Patients must not have clinical evidence of central nervous system involvement by lymphoma; any laboratory or radiographic tests performed within 42 days prior to registration to assess central nervous system (CNS) involvement must be negative
Patients must not have received prior chemotherapy, radiation, or antibody therapy for lymphoma; steroid pre-medication for IV contrast allergy is allowed
Patients must have Zubrod performance status of 0-2
Patients must have serum lactate dehydrogenase (LDH) measured within 28 days prior to registration
Absolute neutrophil count (ANC) > 1,000/mcL within 28 days prior to registration, unless due to bone marrow infiltration by lymphoma
Platelets > 100,000/mcL within 28 days prior to registration, unless due to bone marrow infiltration by lymphoma
Cardiac ejection fraction ≥ institutional lower limit of normal (ILLN) by multigated acquisition (MUGA) scan or 2-dimensional (2-D) echocardiogram (ECHO) with no significant abnormalities within 42 days prior to registration
Patients must not have received valproic acid (a histone deacetylase [HDAC] inhibitor) within 28 days prior to registration
Patients must have no known hypersensitivity to the components of treatment
Patients must be willing to discontinue taking any medications that are generally accepted to have a risk of causing Torsades de Pointes while on study
Patients known to be human immunodeficiency virus (HIV) positive are not eligible; existing therapeutic options are effective and study design does not support assessing the efficacy of treatment on those with HIV
No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
At the time of patient registration, the treating institution's name and identification (ID) number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base
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There are 167 Locations for this study
Mobile Alabama, 36608, United States
Tucson Arizona, 85704, United States
Tucson Arizona, 85719, United States
Tucson Arizona, 85719, United States
Fort Smith Arkansas, 72903, United States
Jonesboro Arkansas, 72401, United States
Jonesboro Arkansas, 72401, United States
Antioch California, 94531, United States
Duarte California, 91010, United States
Fremont California, 94538, United States
Fresno California, 93720, United States
Los Angeles California, 90033, United States
Modesto California, 95356, United States
Oakland California, 94611, United States
Redwood City California, 94063, United States
Richmond California, 94801, United States
Roseville California, 95661, United States
Sacramento California, 95823, United States
Sacramento California, 95825, United States
San Francisco California, 94115, United States
San Jose California, 95119, United States
San Leandro California, 94577, United States
San Rafael California, 94903, United States
Santa Clara California, 95051, United States
Santa Rosa California, 95403, United States
South San Francisco California, 94080, United States
Stockton California, 95210, United States
Vacaville California, 95688, United States
Vallejo California, 94589, United States
Walnut Creek California, 94596, United States
Fort Collins Colorado, 80524, United States
New Haven Connecticut, 06520, United States
Savannah Georgia, 31404, United States
'Aiea Hawaii, 96701, United States
'Aiea Hawaii, 96701, United States
Honolulu Hawaii, 96813, United States
Honolulu Hawaii, 96813, United States
Honolulu Hawaii, 96813, United States
Honolulu Hawaii, 96813, United States
Honolulu Hawaii, 96817, United States
Honolulu Hawaii, 96817, United States
Honolulu Hawaii, 96817, United States
Honolulu Hawaii, 96819, United States
Honolulu Hawaii, 96826, United States
Honolulu Hawaii, 96859, United States
Kailua Hawaii, 96734, United States
Lihue Hawaii, 96766, United States
Geneva Illinois, 60134, United States
Maywood Illinois, 60153, United States
Mount Vernon Illinois, 62864, United States
Warrenville Illinois, 60555, United States
Beech Grove Indiana, 46107, United States
Indianapolis Indiana, 46237, United States
Richmond Indiana, 47374, United States
Chanute Kansas, 66720, United States
Dodge City Kansas, 67801, United States
El Dorado Kansas, 67042, United States
Fort Scott Kansas, 66701, United States
Great Bend Kansas, 67530, United States
Hays Kansas, 67601, United States
Hutchinson Kansas, 67502, United States
Independence Kansas, 67301, United States
Kansas City Kansas, 66112, United States
Kansas City Kansas, 66160, United States
Kingman Kansas, 67068, United States
Lawrence Kansas, 66044, United States
Liberal Kansas, 67905, United States
Newton Kansas, 67114, United States
Overland Park Kansas, 66209, United States
Overland Park Kansas, 66213, United States
Parsons Kansas, 67357, United States
Pittsburg Kansas, 66762, United States
Prairie Village Kansas, 66208, United States
Pratt Kansas, 67124, United States
Salina Kansas, 67401, United States
Salina Kansas, 67401, United States
Topeka Kansas, 66606, United States
Wellington Kansas, 67152, United States
Wichita Kansas, 67208, United States
Wichita Kansas, 67208, United States
Wichita Kansas, 67214, United States
Wichita Kansas, 67214, United States
Wichita Kansas, 67214, United States
Winfield Kansas, 67156, United States
Alexandria Louisiana, 71301, United States
Mansfield Louisiana, 71052, United States
Monroe Louisiana, 71202, United States
Shreveport Louisiana, 71101, United States
Shreveport Louisiana, 71103, United States
Shreveport Louisiana, 71105, United States
Boston Massachusetts, 02118, United States
Burlington Massachusetts, 01805, United States
Battle Creek Michigan, 49017, United States
Big Rapids Michigan, 49307, United States
Grand Rapids Michigan, 49503, United States
Grand Rapids Michigan, 49503, United States
Grand Rapids Michigan, 49503, United States
Muskegon Michigan, 49444, United States
Reed City Michigan, 49677, United States
Traverse City Michigan, 49684, United States
Kansas City Missouri, 64108, United States
Kansas City Missouri, 64111, United States
Kansas City Missouri, 64114, United States
Kansas City Missouri, 64116, United States
Kansas City Missouri, 64118, United States
Kansas City Missouri, 64132, United States
Lee's Summit Missouri, 64086, United States
Liberty Missouri, 64068, United States
Rolla Missouri, 65401, United States
Saint Joseph Missouri, 64506, United States
Saint Louis Missouri, 63109, United States
Saint Louis Missouri, 63141, United States
Springfield Missouri, 65804, United States
Springfield Missouri, 65804, United States
Billings Montana, 59101, United States
Billings Montana, 59101, United States
Billings Montana, 59102, United States
Billings Montana, 59102, United States
Bozeman Montana, 59715, United States
Butte Montana, 59701, United States
Great Falls Montana, 59405, United States
Great Falls Montana, 59405, United States
Helena Montana, 59601, United States
Kalispell Montana, 59901, United States
Kalispell Montana, 59901, United States
Missoula Montana, 59802, United States
Missoula Montana, 59802, United States
Elmira New York, 14905, United States
Rochester New York, 14623, United States
Rochester New York, 14642, United States
Goldsboro North Carolina, 27534, United States
Hendersonville North Carolina, 28791, United States
Hendersonville North Carolina, 28792, United States
Statesville North Carolina, 28677, United States
Winston-Salem North Carolina, 27104, United States
Bellefontaine Ohio, 43311, United States
Chillicothe Ohio, 45601, United States
Cincinnati Ohio, 45219, United States
Columbus Ohio, 43214, United States
Columbus Ohio, 43215, United States
Columbus Ohio, 43215, United States
Columbus Ohio, 43222, United States
Columbus Ohio, 43228, United States
Dayton Ohio, 45405, United States
Dayton Ohio, 45406, United States
Dayton Ohio, 45409, United States
Dayton Ohio, 45415, United States
Dayton Ohio, 45459, United States
Delaware Ohio, 43015, United States
Findlay Ohio, 45840, United States
Franklin Ohio, 45005, United States
Greenville Ohio, 45331, United States
Kettering Ohio, 45429, United States
Lancaster Ohio, 43130, United States
Marietta Ohio, 45750, United States
Mount Vernon Ohio, 43050, United States
Newark Ohio, 43055, United States
Portsmouth Ohio, 45662, United States
Springfield Ohio, 45505, United States
Troy Ohio, 45373, United States
Westerville Ohio, 43081, United States
Wright-Patterson Air Force Base Ohio, 45433, United States
Xenia Ohio, 45385, United States
Zanesville Ohio, 43701, United States
Bend Oregon, 97701, United States
Anderson South Carolina, 29621, United States
Anderson South Carolina, 29621, United States
Greenville South Carolina, 29601, United States
Spartanburg South Carolina, 29303, United States
Anacortes Washington, 98221, United States
Bellingham Washington, 98225, United States
Bremerton Washington, 98310, United States
Burien Washington, 98166, United States
Edmonds Washington, 98026, United States
Issaquah Washington, 98029, United States
Kennewick Washington, 99336, United States
Mount Vernon Washington, 98274, United States
Poulsbo Washington, 98370, United States
Seattle Washington, 98104, United States
Seattle Washington, 98104, United States
Seattle Washington, 98109, United States
Seattle Washington, 98112, United States
Seattle Washington, 98122, United States
Seattle Washington, 98195, United States
Sedro-Woolley Washington, 98284, United States
Spokane Washington, 99202, United States
Spokane Washington, 99218, United States
Wenatchee Washington, 98801, United States
Casper Wyoming, 82609, United States
Sheridan Wyoming, 82801, United States
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