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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)

Phase 1/Phase 2
18 Years
Open (Enrolling)
Contiguous Stage II Adult Diffuse Large Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, Stage III Adult Diffuse Large Cell Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma

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Trial Information

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)


I. To find a safe dose of vorinostat to be used in combination with R-CHOP in patients with
newly diagnosed stage II-IV diffuse large B-cell lymphoma. (Phase I) II. To estimate the
2-year progression-free survival (PFS) rate in patients treated with this regimen. (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 this regimen in these patients. (Phase II)
V. To assess whether pre-treatment acetylation status of histones, expression of MHC Class
II genes, and/or percentage of CD8+ tumor infiltrating lymphocytes correlate with PFS.
(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+, 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, PFS, or overall survival. (Phase II)

OUTLINE: This is a multicenter, 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.

Paraffin block, core needle biopsy, and whole blood samples may be collected at baseline and
during the first course of treatment for further analysis.

After completion of study treatment, patients are followed every 6 months for 2 years, and
then annually for 3 years.

Inclusion Criteria:

- Biopsy-proven* newly diagnosed confirmed diffuse large B-cell lymphoma

- Stage II bulky, stage III, or stage IV disease

- Measurable disease by CT scan or PET/CT of the chest, abdomen, and pelvis within the
past 28 days

- International Prognostic Index (IPI) or Revised-IPI score > 0

- CD20-positive disease

- Adequate sections from the original diagnostic specimen available

- Fine needle aspiration or cytology is not adequate

- No clinical evidence of CNS involvement by lymphoma

- Zubrod performance status 0-2

- ANC > 1,000/mm^3 (unless due to bone marrow infiltration by lymphoma)

- Platelet count > 100,000/mm^3 (unless due to bone marrow infiltration by lymphoma)

- Serum lactate dehydrogenase measured within the past 28 days

- Cardiac ejection fraction normal by MUGA OR 2-dimensional ECHO (2-D ECHO)

- No significant cardiac abnormality by MUGA or 2-D ECHO

- Not pregnant or nursing

- Fertile patients must use effective contraception

- Willing to discontinue any medications that generally have a risk of causing Torsades
de Pointes during study treatment

- No other prior malignancy 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

- Any other cancer from which the patient has been disease-free for 5 years

- No known HIV positivity

- No known hypersensitivity to the components of study treatment

- No prior chemotherapy, radiotherapy, or antibody therapy for lymphoma (steroid
pre-medication for IV contrast allergy allowed)

- More than 28 days since prior valproic acid (a histone deacetylase inhibitor)

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safe dose of vorinostat to be used in combination with R-CHOP assessed by CTCAE Version 4.0 (phase I)

Outcome Time Frame:

21 days

Safety Issue:


Principal Investigator

Daniel Persky

Investigator Role:

Principal Investigator

Investigator Affiliation:

Southwest Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

November 2010

Completion Date:

Related Keywords:

  • Contiguous Stage II Adult Diffuse Large Cell Lymphoma
  • Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma
  • Stage III Adult Diffuse Large Cell Lymphoma
  • Stage IV Adult Diffuse Large Cell Lymphoma
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell



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