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.

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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.

View Eligibility Criteria

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

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 1

Estimated Enrollment:

83

Study ID:

NCT00972478

Recruitment Status:

Active, not recruiting

Sponsor:

National Cancer Institute (NCI)

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There are 167 Locations for this study

See Locations Near You

Providence Hospital
Mobile Alabama, 36608, United States
University of Arizona Cancer Center-Orange Grove Campus
Tucson Arizona, 85704, United States
Banner University Medical Center - Tucson
Tucson Arizona, 85719, United States
University of Arizona Cancer Center-North Campus
Tucson Arizona, 85719, United States
Mercy Hospital Fort Smith
Fort Smith Arkansas, 72903, United States
NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
Jonesboro Arkansas, 72401, United States
NEA Baptist Memorial Hospital
Jonesboro Arkansas, 72401, United States
Kaiser Permanente-Deer Valley Medical Center
Antioch California, 94531, United States
City of Hope Comprehensive Cancer Center
Duarte California, 91010, United States
Kaiser Permanente-Fremont
Fremont California, 94538, United States
Kaiser Permanente-Fresno
Fresno California, 93720, United States
USC / Norris Comprehensive Cancer Center
Los Angeles California, 90033, United States
Kaiser Permanente-Modesto
Modesto California, 95356, United States
Kaiser Permanente-Oakland
Oakland California, 94611, United States
Kaiser Permanente-Redwood City
Redwood City California, 94063, United States
Kaiser Permanente-Richmond
Richmond California, 94801, United States
Kaiser Permanente-Roseville
Roseville California, 95661, United States
Kaiser Permanente-South Sacramento
Sacramento California, 95823, United States
Kaiser Permanente - Sacramento
Sacramento California, 95825, United States
Kaiser Permanente-San Francisco
San Francisco California, 94115, United States
Kaiser Permanente-Santa Teresa-San Jose
San Jose California, 95119, United States
Kaiser Permanente San Leandro
San Leandro California, 94577, United States
Kaiser Permanente-San Rafael
San Rafael California, 94903, United States
Kaiser Permanente Medical Center - Santa Clara
Santa Clara California, 95051, United States
Kaiser Permanente-Santa Rosa
Santa Rosa California, 95403, United States
Kaiser Permanente-South San Francisco
South San Francisco California, 94080, United States
Kaiser Permanente-Stockton
Stockton California, 95210, United States
Kaiser Permanente Medical Center-Vacaville
Vacaville California, 95688, United States
Kaiser Permanente-Vallejo
Vallejo California, 94589, United States
Kaiser Permanente-Walnut Creek
Walnut Creek California, 94596, United States
Poudre Valley Hospital
Fort Collins Colorado, 80524, United States
Yale University
New Haven Connecticut, 06520, United States
Memorial Health University Medical Center
Savannah Georgia, 31404, United States
Pali Momi Medical Center
'Aiea Hawaii, 96701, United States
Queen's Cancer Center - Pearlridge
'Aiea Hawaii, 96701, United States
Hawaii Cancer Care Inc - Waterfront Plaza
Honolulu Hawaii, 96813, United States
Queen's Medical Center
Honolulu Hawaii, 96813, United States
Straub Clinic and Hospital
Honolulu Hawaii, 96813, United States
University of Hawaii Cancer Center
Honolulu Hawaii, 96813, United States
Hawaii Cancer Care Inc-Liliha
Honolulu Hawaii, 96817, United States
Kuakini Medical Center
Honolulu Hawaii, 96817, United States
Queen's Cancer Center - Kuakini
Honolulu Hawaii, 96817, United States
Kaiser Permanente Moanalua Medical Center
Honolulu Hawaii, 96819, United States
Kapiolani Medical Center for Women and Children
Honolulu Hawaii, 96826, United States
Tripler Army Medical Center
Honolulu Hawaii, 96859, United States
Castle Medical Center
Kailua Hawaii, 96734, United States
Wilcox Memorial Hospital and Kauai Medical Clinic
Lihue Hawaii, 96766, United States
Northwestern Medicine Cancer Center Delnor
Geneva Illinois, 60134, United States
Loyola University Medical Center
Maywood Illinois, 60153, United States
Good Samaritan Regional Health Center
Mount Vernon Illinois, 62864, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville Illinois, 60555, United States
Franciscan Saint Francis Health-Beech Grove
Beech Grove Indiana, 46107, United States
Franciscan Health Indianapolis
Indianapolis Indiana, 46237, United States
Reid Health
Richmond Indiana, 47374, United States
Cancer Center of Kansas - Chanute
Chanute Kansas, 66720, United States
Cancer Center of Kansas - Dodge City
Dodge City Kansas, 67801, United States
Cancer Center of Kansas - El Dorado
El Dorado Kansas, 67042, United States
Cancer Center of Kansas - Fort Scott
Fort Scott Kansas, 66701, United States
Saint Rose Ambulatory and Surgery Center
Great Bend Kansas, 67530, United States
HaysMed University of Kansas Health System
Hays Kansas, 67601, United States
Hutchinson Regional Medical Center
Hutchinson Kansas, 67502, United States
Cancer Center of Kansas-Independence
Independence Kansas, 67301, United States
Providence Medical Center
Kansas City Kansas, 66112, United States
University of Kansas Cancer Center
Kansas City Kansas, 66160, United States
Cancer Center of Kansas-Kingman
Kingman Kansas, 67068, United States
Lawrence Memorial Hospital
Lawrence Kansas, 66044, United States
Cancer Center of Kansas-Liberal
Liberal Kansas, 67905, United States
Cancer Center of Kansas - Newton
Newton Kansas, 67114, United States
Menorah Medical Center
Overland Park Kansas, 66209, United States
Saint Luke's South Hospital
Overland Park Kansas, 66213, United States
Cancer Center of Kansas - Parsons
Parsons Kansas, 67357, United States
Ascension Via Christi - Pittsburg
Pittsburg Kansas, 66762, United States
Kansas City NCI Community Oncology Research Program
Prairie Village Kansas, 66208, United States
Cancer Center of Kansas - Pratt
Pratt Kansas, 67124, United States
Cancer Center of Kansas - Salina
Salina Kansas, 67401, United States
Salina Regional Health Center
Salina Kansas, 67401, United States
University of Kansas Health System Saint Francis Campus
Topeka Kansas, 66606, United States
Cancer Center of Kansas - Wellington
Wellington Kansas, 67152, United States
Associates In Womens Health
Wichita Kansas, 67208, United States
Cancer Center of Kansas-Wichita Medical Arts Tower
Wichita Kansas, 67208, United States
Ascension Via Christi Hospitals Wichita
Wichita Kansas, 67214, United States
Cancer Center of Kansas - Wichita
Wichita Kansas, 67214, United States
Wichita NCI Community Oncology Research Program
Wichita Kansas, 67214, United States
Cancer Center of Kansas - Winfield
Winfield Kansas, 67156, United States
Christus Saint Frances Cabrini Hospital
Alexandria Louisiana, 71301, United States
DeSoto Regional Health System
Mansfield Louisiana, 71052, United States
Ochsner LSU Health Monroe Medical Center
Monroe Louisiana, 71202, United States
Overton Brooks Veteran's Administration Medical Center
Shreveport Louisiana, 71101, United States
LSU Health Sciences Center at Shreveport
Shreveport Louisiana, 71103, United States
Highland Clinic
Shreveport Louisiana, 71105, United States
Boston Medical Center
Boston Massachusetts, 02118, United States
Lahey Hospital and Medical Center
Burlington Massachusetts, 01805, United States
Bronson Battle Creek
Battle Creek Michigan, 49017, United States
Spectrum Health Big Rapids Hospital
Big Rapids Michigan, 49307, United States
Cancer Research Consortium of West Michigan NCORP
Grand Rapids Michigan, 49503, United States
Mercy Health Saint Mary's
Grand Rapids Michigan, 49503, United States
Spectrum Health at Butterworth Campus
Grand Rapids Michigan, 49503, United States
Mercy Health Mercy Campus
Muskegon Michigan, 49444, United States
Spectrum Health Reed City Hospital
Reed City Michigan, 49677, United States
Munson Medical Center
Traverse City Michigan, 49684, United States
Truman Medical Centers
Kansas City Missouri, 64108, United States
Saint Luke's Hospital of Kansas City
Kansas City Missouri, 64111, United States
Saint Joseph Health Center
Kansas City Missouri, 64114, United States
North Kansas City Hospital
Kansas City Missouri, 64116, United States
Heartland Hematology and Oncology Associates Incorporated
Kansas City Missouri, 64118, United States
Research Medical Center
Kansas City Missouri, 64132, United States
Saint Luke's East - Lee's Summit
Lee's Summit Missouri, 64086, United States
Liberty Radiation Oncology Center
Liberty Missouri, 64068, United States
Mercy Clinic-Rolla-Cancer and Hematology
Rolla Missouri, 65401, United States
Heartland Regional Medical Center
Saint Joseph Missouri, 64506, United States
Saint Louis Cancer and Breast Institute-South City
Saint Louis Missouri, 63109, United States
Mercy Hospital Saint Louis
Saint Louis Missouri, 63141, United States
Cancer Research for the Ozarks NCORP
Springfield Missouri, 65804, United States
Mercy Hospital Springfield
Springfield Missouri, 65804, United States
Billings Clinic Cancer Center
Billings Montana, 59101, United States
Saint Vincent Healthcare
Billings Montana, 59101, United States
Montana Cancer Consortium NCORP
Billings Montana, 59102, United States
Saint Vincent Frontier Cancer Center
Billings Montana, 59102, United States
Bozeman Deaconess Hospital
Bozeman Montana, 59715, United States
Saint James Community Hospital and Cancer Treatment Center
Butte Montana, 59701, United States
Benefis Healthcare- Sletten Cancer Institute
Great Falls Montana, 59405, United States
Great Falls Clinic
Great Falls Montana, 59405, United States
Saint Peter's Community Hospital
Helena Montana, 59601, United States
Glacier Oncology PLLC
Kalispell Montana, 59901, United States
Kalispell Regional Medical Center
Kalispell Montana, 59901, United States
Montana Cancer Specialists
Missoula Montana, 59802, United States
Saint Patrick Hospital - Community Hospital
Missoula Montana, 59802, United States
Arnot Ogden Medical Center/Falck Cancer Center
Elmira New York, 14905, United States
Interlakes Foundation Inc-Rochester
Rochester New York, 14623, United States
University of Rochester
Rochester New York, 14642, United States
Wayne Memorial Hospital
Goldsboro North Carolina, 27534, United States
Margaret R Pardee Memorial Hospital
Hendersonville North Carolina, 28791, United States
AdventHealth Hendersonville
Hendersonville North Carolina, 28792, United States
Iredell Memorial Hospital
Statesville North Carolina, 28677, United States
Southeast Clinical Oncology Research Consortium NCORP
Winston-Salem North Carolina, 27104, United States
Mary Rutan Hospital
Bellefontaine Ohio, 43311, United States
Adena Regional Medical Center
Chillicothe Ohio, 45601, United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati Ohio, 45219, United States
Riverside Methodist Hospital
Columbus Ohio, 43214, United States
Columbus NCI Community Oncology Research Program
Columbus Ohio, 43215, United States
Grant Medical Center
Columbus Ohio, 43215, United States
Mount Carmel Health Center West
Columbus Ohio, 43222, United States
Doctors Hospital
Columbus Ohio, 43228, United States
Grandview Hospital
Dayton Ohio, 45405, United States
Good Samaritan Hospital - Dayton
Dayton Ohio, 45406, United States
Miami Valley Hospital
Dayton Ohio, 45409, United States
Miami Valley Hospital North
Dayton Ohio, 45415, United States
Dayton NCI Community Oncology Research Program
Dayton Ohio, 45459, United States
Grady Memorial Hospital
Delaware Ohio, 43015, United States
Blanchard Valley Hospital
Findlay Ohio, 45840, United States
Atrium Medical Center-Middletown Regional Hospital
Franklin Ohio, 45005, United States
Wayne Hospital
Greenville Ohio, 45331, United States
Kettering Medical Center
Kettering Ohio, 45429, United States
Fairfield Medical Center
Lancaster Ohio, 43130, United States
Marietta Memorial Hospital
Marietta Ohio, 45750, United States
Knox Community Hospital
Mount Vernon Ohio, 43050, United States
Licking Memorial Hospital
Newark Ohio, 43055, United States
Southern Ohio Medical Center
Portsmouth Ohio, 45662, United States
Springfield Regional Medical Center
Springfield Ohio, 45505, United States
Upper Valley Medical Center
Troy Ohio, 45373, United States
Saint Ann's Hospital
Westerville Ohio, 43081, United States
Wright-Patterson Medical Center
Wright-Patterson Air Force Base Ohio, 45433, United States
Greene Memorial Hospital
Xenia Ohio, 45385, United States
Genesis Healthcare System Cancer Care Center
Zanesville Ohio, 43701, United States
Saint Charles Health System
Bend Oregon, 97701, United States
AnMed Health Cancer Center
Anderson South Carolina, 29621, United States
AnMed Health Hospital
Anderson South Carolina, 29621, United States
Saint Francis Hospital
Greenville South Carolina, 29601, United States
Spartanburg Medical Center
Spartanburg South Carolina, 29303, United States
Cancer Care Center at Island Hospital
Anacortes Washington, 98221, United States
PeaceHealth Saint Joseph Medical Center
Bellingham Washington, 98225, United States
Harrison HealthPartners Hematology and Oncology-Bremerton
Bremerton Washington, 98310, United States
Highline Medical Center-Main Campus
Burien Washington, 98166, United States
Swedish Cancer Institute-Edmonds
Edmonds Washington, 98026, United States
Swedish Cancer Institute-Issaquah
Issaquah Washington, 98029, United States
Kadlec Clinic Hematology and Oncology
Kennewick Washington, 99336, United States
Skagit Valley Hospital
Mount Vernon Washington, 98274, United States
Harrison HealthPartners Hematology and Oncology-Poulsbo
Poulsbo Washington, 98370, United States
Harborview Medical Center
Seattle Washington, 98104, United States
Minor and James Medical PLLC
Seattle Washington, 98104, United States
Fred Hutchinson Cancer Research Center
Seattle Washington, 98109, United States
Kaiser Permanente Washington
Seattle Washington, 98112, United States
Swedish Medical Center-First Hill
Seattle Washington, 98122, United States
University of Washington Medical Center - Montlake
Seattle Washington, 98195, United States
PeaceHealth United General Medical Center
Sedro-Woolley Washington, 98284, United States
Cancer Care Northwest - Spokane South
Spokane Washington, 99202, United States
Evergreen Hematology and Oncology PS
Spokane Washington, 99218, United States
Wenatchee Valley Hospital and Clinics
Wenatchee Washington, 98801, United States
Rocky Mountain Oncology
Casper Wyoming, 82609, United States
Welch Cancer Center
Sheridan Wyoming, 82801, United States

How clear is this clinincal trial information?

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 1

Estimated Enrollment:

83

Study ID:

NCT00972478

Recruitment Status:

Active, not recruiting

Sponsor:


National Cancer Institute (NCI)

How clear is this clinincal trial information?

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