Ann Arbor Stage III Non-Hodgkin Lymphoma, Ann Arbor Stage II Non-Hodgkin Lymphoma, Ann Arbor Stage IV Non-Hodgkin Lymphoma
Conditions
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.
Detailed 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.
Interventions
Given IV
Given IV
Correlative studies
Given IV
Given IV
Given IV
Given PO
Sponsors
Study design
Eligibility
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
United States
Contacts
SWOG Cancer Research Network
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ph I: R-CHOP+Vorinostat (400mg D1-9) 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. | 9 |
| Ph II: R-CHOP+Vorinostat 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. | 63 |
| Total | 72 |
Baseline characteristics
| Characteristic | Ph I: R-CHOP+Vorinostat (400mg D1-9) | Ph II: R-CHOP+Vorinostat | Total |
|---|---|---|---|
| Age, Continuous | 66.9 years | 64.1 years | 64.2 years |
| Race/Ethnicity, Customized Asian | 0 participants | 5 participants | 5 participants |
| Race/Ethnicity, Customized Black | 0 participants | 3 participants | 3 participants |
| Race/Ethnicity, Customized Hispanic | 3 participants | 4 participants | 7 participants |
| Race/Ethnicity, Customized Non-Hispanic | 6 participants | 59 participants | 65 participants |
| Race/Ethnicity, Customized Unknown | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 9 participants | 54 participants | 63 participants |
| Sex: Female, Male Female | 3 Participants | 27 Participants | 30 Participants |
| Sex: Female, Male Male | 6 Participants | 36 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| other Total, other adverse events | 9 / 9 | 63 / 63 |
| serious Total, serious adverse events | 5 / 9 | 44 / 63 |
Outcome results
Progression-free Survival (Phase II)
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
Population: Eligible patients who received the protocol treatment in the Phase II portion of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Progression-free Survival (Phase II) | 73 percentage of participants |
Safe Dose of Vorinostat to be Used in Combination With R-CHOP Assessed by CTCAE Version 4.0 (Phase I)
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Safe Dose of Vorinostat to be Used in Combination With R-CHOP Assessed by CTCAE Version 4.0 (Phase I) | 400 mg PO Once daily Days 1-9 |
Overall Survival (Phase II)
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
Population: Eligible patients who received the protocol treatment in the Phase II portion of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Overall Survival (Phase II) | 86 percentage of participants |
Response Rate (Complete Response [CR]+Partial Response [PR]) (Phase II)
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
Population: Eligible patients who received the protocol treatment in the Phase II portion of the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Response Rate (Complete Response [CR]+Partial Response [PR]) (Phase II) | 81 percentage of participants |
Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Hypophosphatemia | 1 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Disseminated intravascular coagulation | 1 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Hypotension | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | CD4 lymphocytes decreased | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Infections and infestations - Other, specify | 1 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Dizziness | 1 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Jejunal perforation | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Alanine aminotransferase increased | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Left ventricular systolic dysfunction | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Duodenal perforation | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Leukocytosis | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | CPK increased | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Lung infection | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Dysphagia | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Lymphocyte count decreased | 4 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Aspartate aminotransferase increased | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Mucosal infection | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Dyspnea | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Mucositis oral | 1 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Carbon monoxide diffusing capacity decreased | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Multi-organ failure | 1 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Electrocardiogram QT corrected interval prolonged | 1 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Myalgia | 1 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Abdominal pain | 1 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Myocardial infarction | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Fatigue | 3 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Nausea | 1 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Colitis | 1 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Neutrophil count decreased | 8 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Febrile neutropenia | 3 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Obstruction gastric | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Atrial fibrillation | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Pain | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Fecal incontinence | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Paronychia | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Creatinine increased | 1 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Peripheral motor neuropathy | 1 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Gastrointestinal disorders - Other, specify | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Platelet count decreased | 4 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Anemia | 4 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Pneumonitis | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Generalized muscle weakness | 2 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Recurrent laryngeal nerve palsy | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Cystitis noninfective | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Respiratory failure | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Hematuria | 1 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Bladder spasm | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Sinus tachycardia | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Hiccups | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Sinusitis | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Dehydration | 2 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Small intestinal obstruction | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Hyperglycemia | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Stoma site infection | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Acute kidney injury | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Syncope | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Hypoalbuminemia | 1 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Urinary tract infection | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Depression | 1 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Urinary tract pain | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Hypocalcemia | 1 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Urine output decreased | 1 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Bronchial infection | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Vasovagal reaction | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Hypokalemia | 2 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Visceral arterial ischemia | 1 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Diarrhea | 2 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Vomiting | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Hyponatremia | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Weight loss | 0 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Anorexia | 1 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | White blood cell decreased | 7 Participants |
| Ph I: R-CHOP+Vorinostat (400mg D1-9) | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Sepsis | 3 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | White blood cell decreased | 32 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Abdominal pain | 3 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Acute kidney injury | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Alanine aminotransferase increased | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Anemia | 22 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Anorexia | 2 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Aspartate aminotransferase increased | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Atrial fibrillation | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Bladder spasm | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Bronchial infection | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | CD4 lymphocytes decreased | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | CPK increased | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Carbon monoxide diffusing capacity decreased | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Colitis | 0 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Creatinine increased | 0 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Cystitis noninfective | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Dehydration | 4 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Depression | 0 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Diarrhea | 2 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Disseminated intravascular coagulation | 0 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Dizziness | 0 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Duodenal perforation | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Dysphagia | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Dyspnea | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Electrocardiogram QT corrected interval prolonged | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Fatigue | 9 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Febrile neutropenia | 24 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Fecal incontinence | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Gastrointestinal disorders - Other, specify | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Generalized muscle weakness | 2 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Hematuria | 0 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Hiccups | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Hyperglycemia | 4 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Hypoalbuminemia | 3 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Hypocalcemia | 0 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Hypokalemia | 8 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Hyponatremia | 6 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Hypophosphatemia | 2 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Hypotension | 3 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Infections and infestations - Other, specify | 3 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Jejunal perforation | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Left ventricular systolic dysfunction | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Leukocytosis | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Lung infection | 4 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Lymphocyte count decreased | 20 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Mucosal infection | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Mucositis oral | 3 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Multi-organ failure | 0 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Myalgia | 2 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Myocardial infarction | 2 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Nausea | 3 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Neutrophil count decreased | 37 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Obstruction gastric | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Pain | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Paronychia | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Peripheral motor neuropathy | 0 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Platelet count decreased | 22 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Pneumonitis | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Recurrent laryngeal nerve palsy | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Respiratory failure | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Sepsis | 11 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Sinus tachycardia | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Sinusitis | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Small intestinal obstruction | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Stoma site infection | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Syncope | 4 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Urinary tract infection | 3 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Urinary tract pain | 2 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Urine output decreased | 0 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Vasovagal reaction | 1 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Visceral arterial ischemia | 0 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Vomiting | 2 Participants |
| Ph II: R-CHOP+Vorinostat | Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL | Weight loss | 3 Participants |