NCT00972478

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

Active, enrolled Phase 1, PHASE2 Results posted Last updated 9 September 2025

What this trial tests

Phase 1, PHASE2 trial testing Cyclophosphamide in Ann Arbor Stage II Non-Hodgkin Lymphoma in 83 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

15 November 2010

Primary endpoint
30 December 2015

6 March 2026

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 1, PHASE2
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	83
Start date	15 November 2010
Primary completion	30 December 2015
Estimated completion	6 March 2026
Sites	190 locations across United States

Drugs / interventions tested

• Cyclophosphamide (cyclophosphamide) — full drug profile →
• Doxorubicin Hydrochloride — full drug profile →
• Laboratory Biomarker Analysis
• Prednisone (prednisone) — full drug profile →
• Rituximab — full drug profile →
• Vincristine Sulfate (Vincristine Sulfate) — full drug profile →
• Vorinostat

Conditions studied

• Ann Arbor Stage II Non-Hodgkin Lymphoma — all drugs for Ann Arbor Stage II Non-Hodgkin Lymphoma →
• Ann Arbor Stage III Non-Hodgkin Lymphoma — all drugs for Ann Arbor Stage III Non-Hodgkin Lymphoma →
• Ann Arbor Stage IV Non-Hodgkin Lymphoma — all drugs for Ann Arbor Stage IV Non-Hodgkin Lymphoma →

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Ann Arbor Stage II Non-Hodgkin Lymphoma or Ann Arbor Stage III Non-Hodgkin Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Safe Dose of Vorinostat to be Used in Combination With R-CHOP Assessed by CTCAE Version 4.0 (Phase I) Primary · 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).

Group	Value	95% CI
Ph I: R-CHOP+Vorinostat (400mg D1-9)	400

Progression-free Survival (Phase II) Primary · 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.

Group	Value	95% CI
Ph II: R-CHOP+Vorinostat	73	59.6 – 81.9

Overall Survival (Phase II) Secondary · 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.

Group	Value	95% CI
Ph II: R-CHOP+Vorinostat	86	74.3 – 92.3

Response Rate (Complete Response [CR]+Partial Response [PR]) (Phase II) Secondary · 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

Group	Value	95% CI
Ph II: R-CHOP+Vorinostat	81	69.1 – 89.8

Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL Secondary · 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.

Abdominal pain

Group	Value	95% CI
Ph I: R-CHOP+Vorinostat (400mg D1-9)	1
Ph II: R-CHOP+Vorinostat	3

Acute kidney injury

Group	Value	95% CI
Ph I: R-CHOP+Vorinostat (400mg D1-9)	0
Ph II: R-CHOP+Vorinostat	1

Alanine aminotransferase increased

Group	Value	95% CI
Ph I: R-CHOP+Vorinostat (400mg D1-9)	0
Ph II: R-CHOP+Vorinostat	1

Anemia

Group	Value	95% CI
Ph I: R-CHOP+Vorinostat (400mg D1-9)	4
Ph II: R-CHOP+Vorinostat	22

Anorexia

Group	Value	95% CI
Ph I: R-CHOP+Vorinostat (400mg D1-9)	1
Ph II: R-CHOP+Vorinostat	2

Aspartate aminotransferase increased

Group	Value	95% CI
Ph I: R-CHOP+Vorinostat (400mg D1-9)	0
Ph II: R-CHOP+Vorinostat	1

Atrial fibrillation

Group	Value	95% CI
Ph I: R-CHOP+Vorinostat (400mg D1-9)	0
Ph II: R-CHOP+Vorinostat	1

Bladder spasm

Group	Value	95% CI
Ph I: R-CHOP+Vorinostat (400mg D1-9)	0
Ph II: R-CHOP+Vorinostat	1

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to week 26. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Ph I: R-CHOP+Vorinostat (400mg D1-9)

Serious: 5/9 (56%)

Deaths: —

Ph II: R-CHOP+Vorinostat

Serious: 44/63 (70%)

Deaths: —

Serious adverse events (70 terms)

Reaction	System	Ph I: R-CHOP+Vorinostat (4…	Ph II: R-CHOP+Vorinostat
Febrile neutropenia	Blood and lymphatic system disorders	—	—
Neutrophil count decreased	Investigations	—	—
Platelet count decreased	Investigations	—	—
Anemia	Blood and lymphatic system disorders	—	—
White blood cell decreased	Investigations	—	—
Sepsis	Infections and infestations	—	—
Lung infection	Infections and infestations	—	—
Lymphocyte count decreased	Investigations	—	—
Dehydration	Metabolism and nutrition disorders	—	—
Myocardial infarction	Cardiac disorders	—	—
Fatigue	General disorders	—	—
Hypokalemia	Metabolism and nutrition disorders	—	—
Syncope	Nervous system disorders	—	—
Hypotension	Vascular disorders	—	—
Gastrointestinal disorders-Other	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Fever	General disorders	—	—
Pain	General disorders	—	—
Infections and infestations-Other	Infections and infestations	—	—
Urinary tract infection	Infections and infestations	—	—
Creatinine increased	Investigations	—	—
Anorexia	Metabolism and nutrition disorders	—	—
Confusion	Psychiatric disorders	—	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—	—

Other adverse events (122 terms — click to expand)

Reaction	System	Ph I: R-CHOP+Vorinostat (4…	Ph II: R-CHOP+Vorinostat
Anemia	Blood and lymphatic system disorders	—	—
Fatigue	General disorders	—	—
Nausea	Gastrointestinal disorders	—	—
White blood cell decreased	Investigations	—	—
Neutrophil count decreased	Investigations	—	—
Platelet count decreased	Investigations	—	—
Diarrhea	Gastrointestinal disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Lymphocyte count decreased	Investigations	—	—
Anorexia	Metabolism and nutrition disorders	—	—
Hyponatremia	Metabolism and nutrition disorders	—	—
Mucositis oral	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—
Hypoalbuminemia	Metabolism and nutrition disorders	—	—
Hypocalcemia	Metabolism and nutrition disorders	—	—
Dizziness	Nervous system disorders	—	—
Headache	Nervous system disorders	—	—
Peripheral sensory neuropathy	Nervous system disorders	—	—
Fever	General disorders	—	—
Edema limbs	General disorders	—	—
Hypokalemia	Metabolism and nutrition disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Alanine aminotransferase increased	Investigations	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Aspartate aminotransferase increased	Investigations	—	—
Weight loss	Investigations	—	—
Hyperglycemia	Metabolism and nutrition disorders	—	—
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	—	—
Alkaline phosphatase increased	Investigations	—	—
Hypertension	Vascular disorders	—	—
Chills	General disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Insomnia	Psychiatric disorders	—	—
Sinus tachycardia	Cardiac disorders	—	—
Bone pain	Musculoskeletal and connective tissue disorders	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—
Anxiety	Psychiatric disorders	—	—
Blurred vision	Eye disorders	—	—

Most-reported serious reactions: Febrile neutropenia, Neutrophil count decreased, Platelet count decreased, Anemia, White blood cell decreased, Sepsis, Lung infection, Lymphocyte count decreased.

Data from ClinicalTrials.gov NCT00972478 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials.
   Cheng Y, He C, Wang M, Ma X, et al · · 2019 · cited 760× · PMID 31871779 · DOI 10.1038/s41392-019-0095-0
2. Immune checkpoint therapy in liver cancer.
   Xu F, Jin T, Zhu Y, Dai C. · · 2018 · cited 299× · PMID 29843754 · DOI 10.1186/s13046-018-0777-4
3. Synergistic Enhancement of Cancer Therapy Using HDAC Inhibitors: Opportunity for Clinical Trials.
   Hontecillas-Prieto L, Flores-Campos R, Silver A, de Álava E, et al · · 2020 · cited 145× · PMID 33024443 · DOI 10.3389/fgene.2020.578011
4. Epi-drugs in combination with immunotherapy: a new avenue to improve anticancer efficacy.
   Mazzone R, Zwergel C, Mai A, Valente S. · · 2017 · cited 113× · PMID 28572863 · DOI 10.1186/s13148-017-0358-y
5. New agents and regimens for diffuse large B cell lymphoma.
   Wang L, Li LR, Young KH. · · 2020 · cited 109× · PMID 33317571 · DOI 10.1186/s13045-020-01011-z
6. Advances in targeted therapy for malignant lymphoma.
   Wang L, Qin W, Huo YJ, Li X, et al · · 2020 · cited 88× · PMID 32296035 · DOI 10.1038/s41392-020-0113-2
7. Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.
   Zhao A, Zhou H, Yang J, Li M, et al · · 2023 · cited 81× · PMID 36797244 · DOI 10.1038/s41392-023-01342-6
8. A phase I/II trial of vorinostat (SAHA) in combination with rituximab-CHOP in patients with newly diagnosed advanced stage diffuse large B-cell lymphoma (DLBCL): SWOG S0806.
   Persky DO, Li H, Rimsza LM, Barr PM, et al · · 2018 · cited 42× · PMID 29266344 · DOI 10.1002/ajh.25010