Vorinostat, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00972478
• Collaborator: (none)
• Enrollment: 83
• Locations: 190
• Arm: 1
• Patients Per Site: 0.4

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Ann Arbor Stage II Non-Hodgkin Lymphoma; Ann Arbor Stage III Non-Hodgkin Lymphoma; Ann Arbor Stage IV Non-Hodgkin Lymphoma	Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Prednisone; Biological: Rituximab; Drug: Vincristine Sulfate; Drug: Vorinostat	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 83 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Trial of Vorinostat (SAHA) (NSC-701852) in Combination With Rituximab-CHOP in Patients With Newly Diagnosed Advanced Stage Diffuse Large B-Cell Lymphoma (DLBCL)
• Actual Study Start Date: Nov 15, 2010
• Actual Primary Completion Date: Dec 30, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (combination chemotherapy) Patients receive vorinostat PO once daily on days 1-5 or 1-9 (according to dose level), rituximab 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.

Drug: Cyclophosphamide; Given IV; Other Names: (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamide Monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 ; Drug: Doxorubicin Hydrochloride; Given IV; Other Names: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI) ADM Adriacin Adriamycin Adriamycin Hydrochloride Adriamycin PFS Adriamycin RDF ADRIAMYCIN, HYDROCHLORIDE Adriamycine Adriblastina Adriblastine Adrimedac Chloridrato de Doxorrubicina DOX DOXO-CELL Doxolem Doxorubicin HCl Doxorubicin.HCl Doxorubin Farmiblastina FI 106 FI-106 hydroxydaunorubicin Rubex ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Prednisone; Given IV; Other Names: .delta.1-Cortisone 1, 2-Dehydrocortisone Adasone Cortancyl Dacortin DeCortin Decortisyl Decorton Delta 1-Cortisone Delta-Dome Deltacortene Deltacortisone Deltadehydrocortisone Deltasone Deltison Deltra Econosone Lisacort Meprosona-F Metacortandracin Meticorten Ofisolona Orasone Panafcort Panasol-S Paracort Perrigo Prednisone PRED Predicor Predicorten Prednicen-M Prednicort Prednidib Prednilonga Predniment Prednisone Intensol Prednisonum Prednitone Promifen Rayos Servisone SK-Prednisone ; Biological: Rituximab; Given IV; Other Names: ABP 798 BI 695500 C2B8 Monoclonal Antibody Chimeric Anti-CD20 Antibody CT-P10 IDEC-102 IDEC-C2B8 IDEC-C2B8 Monoclonal Antibody MabThera Monoclonal Antibody IDEC-C2B8 PF-05280586 Riabni Rituxan Rituximab ABBS Rituximab ARRX Rituximab Biosimilar ABP 798 Rituximab Biosimilar BI 695500 Rituximab Biosimilar CT-P10 Rituximab Biosimilar GB241 Rituximab Biosimilar IBI301 Rituximab Biosimilar JHL1101 Rituximab Biosimilar PF-05280586 Rituximab Biosimilar RTXM83 Rituximab Biosimilar SAIT101 Rituximab Biosimilar SIBP-02 rituximab biosimilar TQB2303 Rituximab PVVR rituximab-abbs Rituximab-arrx Rituximab-pvvr RTXM83 Ruxience Truxima ; Drug: Vincristine Sulfate; Given IV; Other Names: Kyocristine Leurocristine Sulfate Leurocristine, sulfate Oncovin Vincasar Vincosid Vincrex Vincristine, sulfate ; Drug: Vorinostat; Given PO; Other Names: L-001079038 MSK-390 SAHA Suberanilohydroxamic Acid Suberoylanilide Hydroxamic Acid Zolinza

Outcome Measures

Primary Outcome Measures

1. Safe Dose of Vorinostat to be Used in Combination With R-CHOP Assessed by CTCAE Version 4.0 (Phase I) [21 days]

   Safe dose of Vorinostat (in combination with R-CHOP) at which 3/10 or fewer patients have doselimiting toxicities (DLT). Toxicities graded according to the NCI Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE 4.0). DLT apply only during cycle 1 and should be drug-related (possible, probable, or definite).

2. Progression-free Survival (Phase II) [Up to 2 years]

   From date of registration to date of first documentation of progressive disease, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact.

Secondary Outcome Measures

1. Overall Survival (Phase II) [Up to 2 years]

   From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

2. Response Rate (Complete Response [CR]+Partial Response [PR]) (Phase II) [Up to week 26]

   Objective disease status is evaluated according to the 2007 revised Cheson et al. criteria. Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow (BM) must be negative if positive at baseline. Normalization of markers. Partial Response (PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes.

3. Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL [Up to week 26]

   Incidence of toxicity as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Providence Hospital	Mobile	Alabama	United States	36608
2	University of Arizona Cancer Center-Orange Grove Campus	Tucson	Arizona	United States	85704
3	Banner University Medical Center - Tucson	Tucson	Arizona	United States	85719
4	University of Arizona Cancer Center-North Campus	Tucson	Arizona	United States	85719
5	Mercy Hospital Fort Smith	Fort Smith	Arkansas	United States	72903
6	NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro	Jonesboro	Arkansas	United States	72401
7	NEA Baptist Memorial Hospital	Jonesboro	Arkansas	United States	72401
8	Kaiser Permanente-Deer Valley Medical Center	Antioch	California	United States	94531
9	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
10	Kaiser Permanente-Fremont	Fremont	California	United States	94538
11	Kaiser Permanente-Fresno	Fresno	California	United States	93720
12	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
13	Kaiser Permanente-Modesto	Modesto	California	United States	95356
14	Kaiser Permanente-Oakland	Oakland	California	United States	94611
15	Kaiser Permanente-Redwood City	Redwood City	California	United States	94063
16	Kaiser Permanente-Richmond	Richmond	California	United States	94801
17	Kaiser Permanente-Roseville	Roseville	California	United States	95661
18	Kaiser Permanente-South Sacramento	Sacramento	California	United States	95823
19	Kaiser Permanente - Sacramento	Sacramento	California	United States	95825
20	Kaiser Permanente-San Francisco	San Francisco	California	United States	94115
21	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California	United States	95119
22	Kaiser Permanente San Leandro	San Leandro	California	United States	94577
23	Kaiser Permanente-San Rafael	San Rafael	California	United States	94903
24	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California	United States	95051
25	Kaiser Permanente-Santa Rosa	Santa Rosa	California	United States	95403
26	Kaiser Permanente-South San Francisco	South San Francisco	California	United States	94080
27	Kaiser Permanente-Stockton	Stockton	California	United States	95210
28	Kaiser Permanente Medical Center-Vacaville	Vacaville	California	United States	95688
29	Kaiser Permanente-Vallejo	Vallejo	California	United States	94589
30	Kaiser Permanente-Walnut Creek	Walnut Creek	California	United States	94596
31	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
32	Yale University	New Haven	Connecticut	United States	06520
33	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
34	Pali Momi Medical Center	'Aiea	Hawaii	United States	96701
35	Queen's Cancer Center - Pearlridge	'Aiea	Hawaii	United States	96701
36	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii	United States	96813
37	Queen's Medical Center	Honolulu	Hawaii	United States	96813
38	Straub Clinic and Hospital	Honolulu	Hawaii	United States	96813
39	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
40	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii	United States	96817
41	Kuakini Medical Center	Honolulu	Hawaii	United States	96817
42	Queen's Cancer Center - Kuakini	Honolulu	Hawaii	United States	96817
43	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii	United States	96819
44	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
45	Tripler Army Medical Center	Honolulu	Hawaii	United States	96859
46	Castle Medical Center	Kailua	Hawaii	United States	96734
47	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii	United States	96766
48	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois	United States	60134
49	Loyola University Medical Center	Maywood	Illinois	United States	60153
50	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
51	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois	United States	60555
52	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana	United States	46107
53	Franciscan Health Indianapolis	Indianapolis	Indiana	United States	46237
54	Reid Health	Richmond	Indiana	United States	47374
55	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
56	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
57	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
58	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
59	Saint Rose Ambulatory and Surgery Center	Great Bend	Kansas	United States	67530
60	HaysMed University of Kansas Health System	Hays	Kansas	United States	67601
61	Hutchinson Regional Medical Center	Hutchinson	Kansas	United States	67502
62	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
63	Providence Medical Center	Kansas City	Kansas	United States	66112
64	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
65	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
66	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
67	Cancer Center of Kansas-Liberal	Liberal	Kansas	United States	67905
68	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
69	Menorah Medical Center	Overland Park	Kansas	United States	66209
70	Saint Luke's South Hospital	Overland Park	Kansas	United States	66213
71	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
72	Ascension Via Christi - Pittsburg	Pittsburg	Kansas	United States	66762
73	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas	United States	66208
74	Cancer Center of Kansas - Pratt	Pratt	Kansas	United States	67124
75	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
76	Salina Regional Health Center	Salina	Kansas	United States	67401
77	University of Kansas Health System Saint Francis Campus	Topeka	Kansas	United States	66606
78	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
79	Associates In Womens Health	Wichita	Kansas	United States	67208
80	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
81	Ascension Via Christi Hospitals Wichita	Wichita	Kansas	United States	67214
82	Cancer Center of Kansas - Wichita	Wichita	Kansas	United States	67214
83	Wichita NCI Community Oncology Research Program	Wichita	Kansas	United States	67214
84	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
85	Christus Saint Frances Cabrini Hospital	Alexandria	Louisiana	United States	71301
86	DeSoto Regional Health System	Mansfield	Louisiana	United States	71052
87	Ochsner LSU Health Monroe Medical Center	Monroe	Louisiana	United States	71202
88	Overton Brooks Veteran's Administration Medical Center	Shreveport	Louisiana	United States	71101
89	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana	United States	71103
90	Highland Clinic	Shreveport	Louisiana	United States	71105
91	Boston Medical Center	Boston	Massachusetts	United States	02118
92	Lahey Hospital and Medical Center	Burlington	Massachusetts	United States	01805
93	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
94	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan	United States	49307
95	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan	United States	49503
96	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
97	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
98	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
99	Spectrum Health Reed City Hospital	Reed City	Michigan	United States	49677
100	Munson Medical Center	Traverse City	Michigan	United States	49684
101	Truman Medical Centers	Kansas City	Missouri	United States	64108
102	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
103	Saint Joseph Health Center	Kansas City	Missouri	United States	64114
104	North Kansas City Hospital	Kansas City	Missouri	United States	64116
105	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri	United States	64118
106	Research Medical Center	Kansas City	Missouri	United States	64132
107	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
108	Liberty Radiation Oncology Center	Liberty	Missouri	United States	64068
109	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri	United States	65401
110	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
111	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
112	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
113	Cancer Research for the Ozarks NCORP	Springfield	Missouri	United States	65804
114	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
115	Billings Clinic Cancer Center	Billings	Montana	United States	59101
116	Saint Vincent Healthcare	Billings	Montana	United States	59101
117	Montana Cancer Consortium NCORP	Billings	Montana	United States	59102
118	Saint Vincent Frontier Cancer Center	Billings	Montana	United States	59102
119	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
120	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
121	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
122	Great Falls Clinic	Great Falls	Montana	United States	59405
123	Saint Peter's Community Hospital	Helena	Montana	United States	59601
124	Glacier Oncology PLLC	Kalispell	Montana	United States	59901
125	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
126	Montana Cancer Specialists	Missoula	Montana	United States	59802
127	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
128	Arnot Ogden Medical Center/Falck Cancer Center	Elmira	New York	United States	14905
129	Interlakes Foundation Inc-Rochester	Rochester	New York	United States	14623
130	University of Rochester	Rochester	New York	United States	14642
131	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
132	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28791
133	AdventHealth Hendersonville	Hendersonville	North Carolina	United States	28792
134	Iredell Memorial Hospital	Statesville	North Carolina	United States	28677
135	Southeast Clinical Oncology Research Consortium NCORP	Winston-Salem	North Carolina	United States	27104
136	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
137	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
138	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio	United States	45219
139	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
140	Columbus NCI Community Oncology Research Program	Columbus	Ohio	United States	43215
141	Grant Medical Center	Columbus	Ohio	United States	43215
142	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
143	Doctors Hospital	Columbus	Ohio	United States	43228
144	Grandview Hospital	Dayton	Ohio	United States	45405
145	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
146	Miami Valley Hospital	Dayton	Ohio	United States	45409
147	Miami Valley Hospital North	Dayton	Ohio	United States	45415
148	Dayton NCI Community Oncology Research Program	Dayton	Ohio	United States	45459
149	Grady Memorial Hospital	Delaware	Ohio	United States	43015
150	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
151	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
152	Wayne Hospital	Greenville	Ohio	United States	45331
153	Kettering Medical Center	Kettering	Ohio	United States	45429
154	Fairfield Medical Center	Lancaster	Ohio	United States	43130
155	Marietta Memorial Hospital	Marietta	Ohio	United States	45750
156	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
157	Licking Memorial Hospital	Newark	Ohio	United States	43055
158	Southern Ohio Medical Center	Portsmouth	Ohio	United States	45662
159	Springfield Regional Medical Center	Springfield	Ohio	United States	45505
160	Upper Valley Medical Center	Troy	Ohio	United States	45373
161	Saint Ann's Hospital	Westerville	Ohio	United States	43081
162	Wright-Patterson Medical Center	Wright-Patterson Air Force Base	Ohio	United States	45433
163	Greene Memorial Hospital	Xenia	Ohio	United States	45385
164	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio	United States	43701
165	Saint Charles Health System	Bend	Oregon	United States	97701
166	AnMed Health Cancer Center	Anderson	South Carolina	United States	29621
167	AnMed Health Hospital	Anderson	South Carolina	United States	29621
168	Saint Francis Hospital	Greenville	South Carolina	United States	29601
169	Spartanburg Medical Center	Spartanburg	South Carolina	United States	29303
170	Cancer Care Center at Island Hospital	Anacortes	Washington	United States	98221
171	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
172	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington	United States	98310
173	Highline Medical Center-Main Campus	Burien	Washington	United States	98166
174	Swedish Cancer Institute-Edmonds	Edmonds	Washington	United States	98026
175	Swedish Cancer Institute-Issaquah	Issaquah	Washington	United States	98029
176	Kadlec Clinic Hematology and Oncology	Kennewick	Washington	United States	99336
177	Skagit Valley Hospital	Mount Vernon	Washington	United States	98274
178	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington	United States	98370
179	Harborview Medical Center	Seattle	Washington	United States	98104
180	Minor and James Medical PLLC	Seattle	Washington	United States	98104
181	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
182	Kaiser Permanente Washington	Seattle	Washington	United States	98112
183	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
184	University of Washington Medical Center - Montlake	Seattle	Washington	United States	98195
185	PeaceHealth United General Medical Center	Sedro-Woolley	Washington	United States	98284
186	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
187	Evergreen Hematology and Oncology PS	Spokane	Washington	United States	99218
188	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington	United States	98801
189	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
190	Welch Cancer Center	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Daniel O Persky, Southwest Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00972478
• Other Study ID Numbers: NCI-2011-01964; NCI-2011-01964; CDR0000653803; S0806; S0806; U10CA180888; U10CA032102
• First Posted: Sep 7, 2009
• Last Update Posted: Aug 8, 2022
• Last Verified: Apr 1, 2022

• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse; Prednisone; Cortisone; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Vincristine; Vorinostat; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	Ph I: R-CHOP+Vorinostat (400mg D1-9)	Ph II: R-CHOP+Vorinostat
Arm/Group Description	Patients receive vorinostat 400 mg PO once daily on days 1-9 (according to dose level), rituximab 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.	Patients receive vorinostat 400 mg PO once daily on days 1-5 or 1-9 (according to dose level), rituximab 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.
Period Title: Overall Study
STARTED	11	72
Eligible and Began Protocol Therapy	9	63
COMPLETED	4	34
NOT COMPLETED	7	38

Baseline Characteristics

Arm/Group Title	Ph I: R-CHOP+Vorinostat (400mg D1-9)	Ph II: R-CHOP+Vorinostat	Total
Arm/Group Description	Patients receive vorinostat 400 mg PO once daily on days 1-9 (according to dose level), rituximab 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.	Patients receive vorinostat 400 mg PO once daily on days 1-5 or 1-9 (according to dose level), rituximab 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.	Total of all reporting groups
Overall Participants	9	63	72
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	66.9	64.1	64.2
Sex: Female, Male (Count of Participants)
Female	3 33.3%	27 42.9%	30 41.7%
Male	6 66.7%	36 57.1%	42 58.3%
Race/Ethnicity, Customized (participants) [Number]
White	9 100%	54 85.7%	63 87.5%
Black	0 0%	3 4.8%	3 4.2%
Asian	0 0%	5 7.9%	5 6.9%
Unknown	0 0%	1 1.6%	1 1.4%
Race/Ethnicity, Customized (participants) [Number]
Hispanic	3 33.3%	4 6.3%	7 9.7%
Non-Hispanic	6 66.7%	59 93.7%	65 90.3%

Outcome Measures

1. Primary Outcome

Title	Safe Dose of Vorinostat to be Used in Combination With R-CHOP Assessed by CTCAE Version 4.0 (Phase I)
Description	Safe dose of Vorinostat (in combination with R-CHOP) at which 3/10 or fewer patients have doselimiting toxicities (DLT). Toxicities graded according to the NCI Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE 4.0). DLT apply only during cycle 1 and should be drug-related (possible, probable, or definite).
Time Frame	21 days

Outcome Measure Data

Analysis Population Description

Phase I eligible patients receiving any amount of the assigned dose during Cycle 1 (1 Cycle = 21 days) or whom developed a dose-limiting toxicity (DLT).

Arm/Group Title	Ph I: R-CHOP+Vorinostat (400mg D1-9)
Arm/Group Description	Patients receive vorinostat 400 mg PO once daily on days 1-9 (according to dose level), rituximab 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.
Measure Participants	9
Number [mg PO Once daily Days 1-9]	400

2. Primary Outcome

Title	Progression-free Survival (Phase II)
Description	From date of registration to date of first documentation of progressive disease, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Eligible patients who received the protocol treatment in the Phase II portion of the study.

Arm/Group Title	Ph II: R-CHOP+Vorinostat
Arm/Group Description	Patients receive vorinostat 400 mg PO once daily on days 1-5 or 1-9 (according to dose level), rituximab 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.
Measure Participants	63
Number (95% Confidence Interval) [percentage of participants]	73 811.1%

3. Secondary Outcome

Title	Overall Survival (Phase II)
Description	From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Eligible patients who received the protocol treatment in the Phase II portion of the study.

Arm/Group Title	Ph II: R-CHOP+Vorinostat
Arm/Group Description	Patients receive vorinostat 400 mg PO once daily on days 1-5 or 1-9 (according to dose level), rituximab 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.
Measure Participants	63
Number (95% Confidence Interval) [percentage of participants]	86 955.6%

4. Secondary Outcome

Title	Response Rate (Complete Response [CR]+Partial Response [PR]) (Phase II)
Description	Objective disease status is evaluated according to the 2007 revised Cheson et al. criteria. Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow (BM) must be negative if positive at baseline. Normalization of markers. Partial Response (PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes.
Time Frame	Up to week 26

Outcome Measure Data

Analysis Population Description

Eligible patients who received the protocol treatment in the Phase II portion of the study

Arm/Group Title	Ph II: R-CHOP+Vorinostat
Arm/Group Description	Patients receive vorinostat 400 mg PO once daily on days 1-5 or 1-9 (according to dose level), rituximab 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.
Measure Participants	63
Number (95% Confidence Interval) [percentage of participants]	81 900%

5. Secondary Outcome

Title	Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL
Description	Incidence of toxicity as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
Time Frame	Up to week 26

Outcome Measure Data

Analysis Population Description

Eligible patients who had received any treatment were included in the adverse event summaries. Any CTCAE 4.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which deemed to be related to protocol treatment are included.

Arm/Group Title	Ph I: R-CHOP+Vorinostat (400mg D1-9)	Ph II: R-CHOP+Vorinostat
Arm/Group Description	Patients receive vorinostat 400 mg PO once daily on days 1-9 (according to dose level), rituximab 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.	Patients receive vorinostat 400 mg PO once daily on days 1-5 or 1-9 (according to dose level), rituximab 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.
Measure Participants	9	63
Abdominal pain	1 11.1%	3 4.8%
Acute kidney injury	0 0%	1 1.6%
Alanine aminotransferase increased	0 0%	1 1.6%
Anemia	4 44.4%	22 34.9%
Anorexia	1 11.1%	2 3.2%
Aspartate aminotransferase increased	0 0%	1 1.6%
Atrial fibrillation	0 0%	1 1.6%
Bladder spasm	0 0%	1 1.6%
Bronchial infection	0 0%	1 1.6%
CD4 lymphocytes decreased	0 0%	1 1.6%
CPK increased	0 0%	1 1.6%
Carbon monoxide diffusing capacity decreased	0 0%	1 1.6%
Colitis	1 11.1%	0 0%
Creatinine increased	1 11.1%	0 0%
Cystitis noninfective	0 0%	1 1.6%
Dehydration	2 22.2%	4 6.3%
Depression	1 11.1%	0 0%
Diarrhea	2 22.2%	2 3.2%
Disseminated intravascular coagulation	1 11.1%	0 0%
Dizziness	1 11.1%	0 0%
Duodenal perforation	0 0%	1 1.6%
Dysphagia	0 0%	1 1.6%
Dyspnea	0 0%	1 1.6%
Electrocardiogram QT corrected interval prolonged	1 11.1%	1 1.6%
Fatigue	3 33.3%	9 14.3%
Febrile neutropenia	3 33.3%	24 38.1%
Fecal incontinence	0 0%	1 1.6%
Gastrointestinal disorders - Other, specify	0 0%	1 1.6%
Generalized muscle weakness	2 22.2%	2 3.2%
Hematuria	1 11.1%	0 0%
Hiccups	0 0%	1 1.6%
Hyperglycemia	0 0%	4 6.3%
Hypoalbuminemia	1 11.1%	3 4.8%
Hypocalcemia	1 11.1%	0 0%
Hypokalemia	2 22.2%	8 12.7%
Hyponatremia	0 0%	6 9.5%
Hypophosphatemia	1 11.1%	2 3.2%
Hypotension	0 0%	3 4.8%
Infections and infestations - Other, specify	1 11.1%	3 4.8%
Jejunal perforation	0 0%	1 1.6%
Left ventricular systolic dysfunction	0 0%	1 1.6%
Leukocytosis	0 0%	1 1.6%
Lung infection	0 0%	4 6.3%
Lymphocyte count decreased	4 44.4%	20 31.7%
Mucosal infection	0 0%	1 1.6%
Mucositis oral	1 11.1%	3 4.8%
Multi-organ failure	1 11.1%	0 0%
Myalgia	1 11.1%	2 3.2%
Myocardial infarction	0 0%	2 3.2%
Nausea	1 11.1%	3 4.8%
Neutrophil count decreased	8 88.9%	37 58.7%
Obstruction gastric	0 0%	1 1.6%
Pain	0 0%	1 1.6%
Paronychia	0 0%	1 1.6%
Peripheral motor neuropathy	1 11.1%	0 0%
Platelet count decreased	4 44.4%	22 34.9%
Pneumonitis	0 0%	1 1.6%
Recurrent laryngeal nerve palsy	0 0%	1 1.6%
Respiratory failure	0 0%	1 1.6%
Sepsis	3 33.3%	11 17.5%
Sinus tachycardia	0 0%	1 1.6%
Sinusitis	0 0%	1 1.6%
Small intestinal obstruction	0 0%	1 1.6%
Stoma site infection	0 0%	1 1.6%
Syncope	0 0%	4 6.3%
Urinary tract infection	0 0%	3 4.8%
Urinary tract pain	0 0%	2 3.2%
Urine output decreased	1 11.1%	0 0%
Vasovagal reaction	0 0%	1 1.6%
Visceral arterial ischemia	1 11.1%	0 0%
Vomiting	0 0%	2 3.2%
Weight loss	0 0%	3 4.8%
White blood cell decreased	7 77.8%	32 50.8%

Adverse Events

Time Frame	Up to week 26
Adverse Event Reporting Description	Eligible patients who had received any treatment were included. Incidence of toxicity as assessed by the Common Terminology Criteria for Adverse Events version 4.0.
Arm/Group Title	Ph I: R-CHOP+Vorinostat (400mg D1-9)		Ph II: R-CHOP+Vorinostat
Arm/Group Description	Patients receive vorinostat 400 mg PO once daily on days 1-9 (according to dose level), rituximab 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.		Patients receive vorinostat 400 mg PO once daily on days 1-5 or 1-9 (according to dose level), rituximab 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.
All Cause Mortality
	Ph I: R-CHOP+Vorinostat (400mg D1-9)		Ph II: R-CHOP+Vorinostat
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ph I: R-CHOP+Vorinostat (400mg D1-9)		Ph II: R-CHOP+Vorinostat
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/9 (55.6%)		44/63 (69.8%)
Blood and lymphatic system disorders
Anemia	3/9 (33.3%)		13/63 (20.6%)
Disseminated intravascular coagulation	1/9 (11.1%)		0/63 (0%)
Febrile neutropenia	3/9 (33.3%)		22/63 (34.9%)
Cardiac disorders
Atrial fibrillation	0/9 (0%)		1/63 (1.6%)
Cardiac arrest	0/9 (0%)		1/63 (1.6%)
Left ventricular systolic dysfunction	0/9 (0%)		1/63 (1.6%)
Myocardial infarction	0/9 (0%)		3/63 (4.8%)
Gastrointestinal disorders
Abdominal pain	1/9 (11.1%)		1/63 (1.6%)
Colitis	1/9 (11.1%)		0/63 (0%)
Constipation	0/9 (0%)		1/63 (1.6%)
Diarrhea	0/9 (0%)		1/63 (1.6%)
Dysphagia	0/9 (0%)		1/63 (1.6%)
Gastroesophageal reflux disease	0/9 (0%)		1/63 (1.6%)
Gastrointestinal disorders-Other	0/9 (0%)		2/63 (3.2%)
Jejunal perforation	0/9 (0%)		1/63 (1.6%)
Mucositis oral	1/9 (11.1%)		0/63 (0%)
Nausea	0/9 (0%)		2/63 (3.2%)
Small intestinal obstruction	0/9 (0%)		1/63 (1.6%)
Vomiting	0/9 (0%)		2/63 (3.2%)
General disorders
Death NOS	0/9 (0%)		1/63 (1.6%)
Fatigue	1/9 (11.1%)		3/63 (4.8%)
Fever	0/9 (0%)		2/63 (3.2%)
Malaise	0/9 (0%)		1/63 (1.6%)
Multi-organ failure	1/9 (11.1%)		0/63 (0%)
Non-cardiac chest pain	0/9 (0%)		1/63 (1.6%)
Pain	0/9 (0%)		2/63 (3.2%)
Infections and infestations
Bronchial infection	0/9 (0%)		1/63 (1.6%)
Infections and infestations-Other	0/9 (0%)		2/63 (3.2%)
Lung infection	1/9 (11.1%)		4/63 (6.3%)
Paronychia	0/9 (0%)		1/63 (1.6%)
Sepsis	3/9 (33.3%)		8/63 (12.7%)
Sinusitis	0/9 (0%)		1/63 (1.6%)
Stoma site infection	0/9 (0%)		1/63 (1.6%)
Urinary tract infection	0/9 (0%)		2/63 (3.2%)
Investigations
Aspartate aminotransferase increased	0/9 (0%)		1/63 (1.6%)
Creatinine increased	1/9 (11.1%)		2/63 (3.2%)
Electrocardiogram QT corrected interval prolonged	1/9 (11.1%)		1/63 (1.6%)
Lymphocyte count decreased	1/9 (11.1%)		4/63 (6.3%)
Neutrophil count decreased	3/9 (33.3%)		16/63 (25.4%)
Platelet count decreased	4/9 (44.4%)		16/63 (25.4%)
Weight loss	0/9 (0%)		1/63 (1.6%)
White blood cell decreased	2/9 (22.2%)		10/63 (15.9%)
Metabolism and nutrition disorders
Anorexia	0/9 (0%)		2/63 (3.2%)
Dehydration	1/9 (11.1%)		4/63 (6.3%)
Hypercalcemia	0/9 (0%)		1/63 (1.6%)
Hypoalbuminemia	0/9 (0%)		1/63 (1.6%)
Hypocalcemia	1/9 (11.1%)		0/63 (0%)
Hypokalemia	2/9 (22.2%)		3/63 (4.8%)
Hypophosphatemia	1/9 (11.1%)		0/63 (0%)
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	0/9 (0%)		1/63 (1.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified - Other	0/9 (0%)		1/63 (1.6%)
Nervous system disorders
Cognitive disturbance	0/9 (0%)		1/63 (1.6%)
Dizziness	0/9 (0%)		1/63 (1.6%)
Recurrent laryngeal nerve palsy	0/9 (0%)		1/63 (1.6%)
Reversible posterior leukoencephalopathy syndrome	0/9 (0%)		1/63 (1.6%)
Syncope	0/9 (0%)		3/63 (4.8%)
Psychiatric disorders
Confusion	0/9 (0%)		2/63 (3.2%)
Renal and urinary disorders
Acute kidney injury	0/9 (0%)		1/63 (1.6%)
Cystitis noninfective	0/9 (0%)		1/63 (1.6%)
Urinary frequency	0/9 (0%)		1/63 (1.6%)
Urinary tract pain	0/9 (0%)		1/63 (1.6%)
Respiratory, thoracic and mediastinal disorders
Cough	0/9 (0%)		1/63 (1.6%)
Dyspnea	0/9 (0%)		1/63 (1.6%)
Hiccups	0/9 (0%)		1/63 (1.6%)
Pneumonitis	0/9 (0%)		2/63 (3.2%)
Pulmonary edema	0/9 (0%)		1/63 (1.6%)
Respiratory failure	0/9 (0%)		1/63 (1.6%)
Vascular disorders
Hypotension	0/9 (0%)		3/63 (4.8%)
Thromboembolic event	0/9 (0%)		2/63 (3.2%)
Visceral arterial ischemia	1/9 (11.1%)		0/63 (0%)
Other (Not Including Serious) Adverse Events
	Ph I: R-CHOP+Vorinostat (400mg D1-9)		Ph II: R-CHOP+Vorinostat
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/9 (100%)		63/63 (100%)
Blood and lymphatic system disorders
Anemia	9/9 (100%)		52/63 (82.5%)
Cardiac disorders
Sinus tachycardia	0/9 (0%)		9/63 (14.3%)
Eye disorders
Blurred vision	2/9 (22.2%)		8/63 (12.7%)
Dry eye	2/9 (22.2%)		0/63 (0%)
Eye disorders-Other	1/9 (11.1%)		0/63 (0%)
Photophobia	1/9 (11.1%)		0/63 (0%)
Watering eyes	1/9 (11.1%)		0/63 (0%)
Gastrointestinal disorders
Abdominal pain	2/9 (22.2%)		16/63 (25.4%)
Bloating	1/9 (11.1%)		3/63 (4.8%)
Constipation	5/9 (55.6%)		26/63 (41.3%)
Diarrhea	7/9 (77.8%)		31/63 (49.2%)
Dry mouth	3/9 (33.3%)		6/63 (9.5%)
Dyspepsia	0/9 (0%)		4/63 (6.3%)
Fecal incontinence	1/9 (11.1%)		1/63 (1.6%)
Gastrointestinal disorders-Other	2/9 (22.2%)		2/63 (3.2%)
Hemorrhoids	0/9 (0%)		4/63 (6.3%)
Mucositis oral	1/9 (11.1%)		22/63 (34.9%)
Nausea	8/9 (88.9%)		43/63 (68.3%)
Oral pain	1/9 (11.1%)		2/63 (3.2%)
Rectal mucositis	1/9 (11.1%)		0/63 (0%)
Vomiting	4/9 (44.4%)		22/63 (34.9%)
General disorders
Chills	2/9 (22.2%)		10/63 (15.9%)
Edema face	3/9 (33.3%)		0/63 (0%)
Edema limbs	2/9 (22.2%)		17/63 (27%)
Fatigue	8/9 (88.9%)		45/63 (71.4%)
Fever	1/9 (11.1%)		18/63 (28.6%)
Gait disturbance	2/9 (22.2%)		3/63 (4.8%)
Infusion related reaction	0/9 (0%)		4/63 (6.3%)
Non-cardiac chest pain	0/9 (0%)		4/63 (6.3%)
Pain	4/9 (44.4%)		7/63 (11.1%)
Infections and infestations
Infections and infestations-Other	1/9 (11.1%)		4/63 (6.3%)
Mucosal infection	1/9 (11.1%)		3/63 (4.8%)
Peripheral nerve infection	1/9 (11.1%)		0/63 (0%)
Rhinitis infective	1/9 (11.1%)		2/63 (3.2%)
Skin infection	1/9 (11.1%)		5/63 (7.9%)
Urinary tract infection	1/9 (11.1%)		5/63 (7.9%)
Wound infection	1/9 (11.1%)		0/63 (0%)
Injury, poisoning and procedural complications
Bruising	2/9 (22.2%)		3/63 (4.8%)
Fall	1/9 (11.1%)		2/63 (3.2%)
Fracture	1/9 (11.1%)		0/63 (0%)
Investigations
Activated partial thromboplastin time prolonged	1/9 (11.1%)		0/63 (0%)
Alanine aminotransferase increased	2/9 (22.2%)		16/63 (25.4%)
Alkaline phosphatase increased	0/9 (0%)		11/63 (17.5%)
Aspartate aminotransferase increased	2/9 (22.2%)		13/63 (20.6%)
Blood bilirubin increased	1/9 (11.1%)		4/63 (6.3%)
CD4 lymphocytes decreased	0/9 (0%)		4/63 (6.3%)
Cardiac troponin I increased	1/9 (11.1%)		1/63 (1.6%)
Creatinine increased	1/9 (11.1%)		6/63 (9.5%)
Electrocardiogram QT corrected interval prolonged	0/9 (0%)		5/63 (7.9%)
Investigations-Other	2/9 (22.2%)		0/63 (0%)
Lymphocyte count decreased	7/9 (77.8%)		26/63 (41.3%)
Neutrophil count decreased	7/9 (77.8%)		35/63 (55.6%)
Platelet count decreased	8/9 (88.9%)		32/63 (50.8%)
Urine output decreased	1/9 (11.1%)		0/63 (0%)
Weight gain	2/9 (22.2%)		4/63 (6.3%)
Weight loss	2/9 (22.2%)		13/63 (20.6%)
White blood cell decreased	8/9 (88.9%)		40/63 (63.5%)
Metabolism and nutrition disorders
Anorexia	6/9 (66.7%)		23/63 (36.5%)
Dehydration	2/9 (22.2%)		7/63 (11.1%)
Hyperglycemia	2/9 (22.2%)		12/63 (19%)
Hyperkalemia	2/9 (22.2%)		0/63 (0%)
Hypoalbuminemia	4/9 (44.4%)		20/63 (31.7%)
Hypocalcemia	3/9 (33.3%)		20/63 (31.7%)
Hypoglycemia	1/9 (11.1%)		4/63 (6.3%)
Hypokalemia	4/9 (44.4%)		17/63 (27%)
Hypomagnesemia	1/9 (11.1%)		8/63 (12.7%)
Hyponatremia	4/9 (44.4%)		23/63 (36.5%)
Hypophosphatemia	1/9 (11.1%)		7/63 (11.1%)
Metabolism and nutrition disorders - Other, specify	2/9 (22.2%)		1/63 (1.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/9 (0%)		8/63 (12.7%)
Back pain	1/9 (11.1%)		10/63 (15.9%)
Bone pain	4/9 (44.4%)		9/63 (14.3%)
Chest wall pain	2/9 (22.2%)		5/63 (7.9%)
Flank pain	1/9 (11.1%)		0/63 (0%)
Generalized muscle weakness	5/9 (55.6%)		12/63 (19%)
Muscle weakness upper limb	1/9 (11.1%)		0/63 (0%)
Myalgia	1/9 (11.1%)		9/63 (14.3%)
Neck pain	0/9 (0%)		4/63 (6.3%)
Pain in extremity	2/9 (22.2%)		4/63 (6.3%)
Nervous system disorders
Dizziness	4/9 (44.4%)		20/63 (31.7%)
Dysgeusia	3/9 (33.3%)		8/63 (12.7%)
Headache	4/9 (44.4%)		20/63 (31.7%)
Lethargy	1/9 (11.1%)		1/63 (1.6%)
Memory impairment	1/9 (11.1%)		0/63 (0%)
Movements involuntary	1/9 (11.1%)		0/63 (0%)
Paresthesia	3/9 (33.3%)		1/63 (1.6%)
Peripheral motor neuropathy	5/9 (55.6%)		4/63 (6.3%)
Peripheral sensory neuropathy	4/9 (44.4%)		19/63 (30.2%)
Tremor	1/9 (11.1%)		0/63 (0%)
Psychiatric disorders
Agitation	1/9 (11.1%)		0/63 (0%)
Anxiety	1/9 (11.1%)		9/63 (14.3%)
Confusion	1/9 (11.1%)		1/63 (1.6%)
Depression	3/9 (33.3%)		6/63 (9.5%)
Insomnia	6/9 (66.7%)		10/63 (15.9%)
Renal and urinary disorders
Hematuria	1/9 (11.1%)		4/63 (6.3%)
Proteinuria	0/9 (0%)		7/63 (11.1%)
Renal and urinary disorders-Other	1/9 (11.1%)		1/63 (1.6%)
Urinary frequency	6/9 (66.7%)		5/63 (7.9%)
Urinary incontinence	1/9 (11.1%)		2/63 (3.2%)
Urinary retention	1/9 (11.1%)		0/63 (0%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/9 (11.1%)		3/63 (4.8%)
Cough	5/9 (55.6%)		15/63 (23.8%)
Dyspnea	2/9 (22.2%)		16/63 (25.4%)
Hiccups	2/9 (22.2%)		3/63 (4.8%)
Hypoxia	2/9 (22.2%)		0/63 (0%)
Postnasal drip	2/9 (22.2%)		1/63 (1.6%)
Resp, thoracic and mediastinal disorders - Other	1/9 (11.1%)		0/63 (0%)
Sore throat	1/9 (11.1%)		5/63 (7.9%)
Skin and subcutaneous tissue disorders
Alopecia	7/9 (77.8%)		21/63 (33.3%)
Dry skin	1/9 (11.1%)		3/63 (4.8%)
Erythema multiforme	2/9 (22.2%)		0/63 (0%)
Hyperhidrosis	2/9 (22.2%)		2/63 (3.2%)
Nail discoloration	2/9 (22.2%)		3/63 (4.8%)
Pruritus	1/9 (11.1%)		3/63 (4.8%)
Rash maculo-papular	4/9 (44.4%)		4/63 (6.3%)
Skin and subcutaneous tissue disorders - Other	2/9 (22.2%)		4/63 (6.3%)
Skin hyperpigmentation	1/9 (11.1%)		0/63 (0%)
Vascular disorders
Hematoma	1/9 (11.1%)		0/63 (0%)
Hot flashes	1/9 (11.1%)		5/63 (7.9%)
Hypertension	4/9 (44.4%)		11/63 (17.5%)
Hypotension	2/9 (22.2%)		8/63 (12.7%)
Thromboembolic event	1/9 (11.1%)		4/63 (6.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.