Vorinostat, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma
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|ClinicalTrials.gov Identifier: NCT00972478|
Recruitment Status : Active, not recruiting
First Posted : September 7, 2009
Results First Posted : October 31, 2016
Last Update Posted : October 29, 2019
|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|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||83 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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 :||November 15, 2010|
|Actual Primary Completion Date :||December 30, 2015|
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: Doxorubicin Hydrochloride
Other: Laboratory Biomarker Analysis
Drug: Vincristine Sulfate
- Safe Dose of Vorinostat to be Used in Combination With R-CHOP Assessed by CTCAE Version 4.0 (Phase I) [ Time Frame: 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) [ Time Frame: 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.
- Overall Survival (Phase II) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00972478
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|Principal Investigator:||Daniel O Persky||Southwest Oncology Group|