Know Cancer

or
forgot password

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
N/A
Open (Enrolling)
Both
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

Thank you

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)


OBJECTIVES:

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:

Interventional

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:

Yes

Principal Investigator

Daniel Persky

Investigator Role:

Principal Investigator

Investigator Affiliation:

Southwest Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-01964

NCT ID:

NCT00972478

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

Name

Location

Louisiana State UniversityNew Orleans, Louisiana  70112-2282
University of Washington Medical CenterSeattle, Washington  98195-6043
Tripler Army Medical CenterHonolulu, Hawaii  96859-5000
Loyola University Medical CenterMaywood, Illinois  60153
Boston Medical CenterBoston, Massachusetts  02118
Kaiser Permanente Medical Center - Santa ClaraSanta Clara, California  95051-5386
Via Christi Regional Medical CenterWichita, Kansas  67214
Group Health CooperativeSeattle, Washington  98112
Great Falls ClinicGreat Falls, Montana  59405
Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109
Cancer Center of Kansas - ChanuteChanute, Kansas  66720
Cancer Center of Kansas - Dodge CityDodge City, Kansas  67801
Cancer Center of Kansas - NewtonNewton, Kansas  67114
Cancer Center of Kansas - SalinaSalina, Kansas  67042
Cancer Center of Kansas - WellingtonWellington, Kansas  67152
Associates in Womens HealthWichita, Kansas  67203
Cancer Center of Kansas - WinfieldWinfield, Kansas  67156
Munson Medical CenterTraverse City, Michigan  49684
Bozeman Deaconess HospitalBozeman, Montana  59715
Kalispell Regional Medical CenterKalispell, Montana  59901
Adena Regional Medical CenterChillicothe, Ohio  54601
Grady Memorial HospitalDelaware, Ohio  43015
Fairfield Medical CenterLancaster, Ohio  43130
Harborview Medical CenterSeattle, Washington  98104
Cancer Care Northwest - Spokane SouthSpokane, Washington  99202
Welch Cancer CenterSheridan, Wyoming  82801
City of Hope Medical CenterDuarte, California  91010
Front Range Cancer SpecialistsFort Collins, Colorado  80528
Poudre Valley HospitalFort Collins, Colorado  80524
Mecosta County Medical CenterBig Rapids, Michigan  49307
Iredell Memorial HospitalStatesville, North Carolina  28677
Grandview HospitalDayton, Ohio  45405
Miami Valley HospitalDayton, Ohio  45409
Spartanburg Regional Medical CenterSpartanburg, South Carolina  29303
Cancer Center of Kansas - Fort ScottFort Scott, Kansas  66701
Cancer Center of Kansas-IndependenceIndependence, Kansas  67301
Lawrence Memorial HospitalLawrence, Kansas  66044
Menorah Medical CenterOverland Park, Kansas  66209
North Kansas City HospitalKansas City, Missouri  64116
Research Medical CenterKansas City, Missouri  64132
Saint Luke's East - Lee's SummitLee's Summit, Missouri  64086
Heartland Regional Medical CenterSaint Joseph, Missouri  64506
Bozeman Deaconess Cancer CenterBozeman, Montana  59715
Mary Rutan HospitalBellefontaine, Ohio  43311
Wayne HospitalGreenville, Ohio  45331
Knox Community HospitalMount Vernon, Ohio  43050
Wenatchee Valley Medical CenterWenatchee, Washington  98801-2028
Rocky Mountain OncologyCasper, Wyoming  82609
Greene Memorial HospitalXenia, Ohio  45385
AnMed Health Cancer CenterAnderson, South Carolina  29621
Queen's Medical CenterHonolulu, Hawaii  96813
Providence HospitalMobile, Alabama  36608
Providence Medical CenterKansas City, Kansas  66112
Kapiolani Medical Center at Pali MomiAiea, Hawaii  96701
Kapiolani Medical Center for Women and ChildrenHonolulu, Hawaii  96826
University of RochesterRochester, New York  14642
Yale UniversityNew Haven, Connecticut  06520
University of Arizona Health Sciences CenterTucson, Arizona  85724
Straub Clinic and HospitalHonolulu, Hawaii  96813
Riverside Methodist HospitalColumbus, Ohio  43214
Licking Memorial HospitalNewark, Ohio  43055-2899
Columbus CCOPColumbus, Ohio  43206
Kaiser PermanenteSacramento, California  
Wichita CCOPWichita, Kansas  67214-3882
Montana Cancer Consortium CCOPBillings, Montana  59101
Montana Cancer SpecialistsMissoula, Montana  59807-7877
Memorial Health University Medical CenterSavannah, Georgia  31404
University of Southern CaliforniaLos Angeles, California  90033
University of CincinnatiCincinnati, Ohio  45267-0502
Castle Medical CenterKailua, Hawaii  96734
Saint Edward Mercy Medical CenterFt. Smith, Arkansas  72903
Kaiser Permanente, FremontFremont, California  94538
Kaiser Permanente, HaywardHayward, California  94545
Kaiser Permanente-OaklandOakland, California  94611
Kaiser Permanente-Redwood CityRedwood City, California  94063
Kaiser Permanente-RichmondRichmond, California  94801
Kaiser Permanente-RosevilleRoseville, California  95661
Kaiser Permanente-South SacramentoSacramento, California  95823
Kaiser Permanente - SacramentoSacramento, California  95825
Kaiser Permanente-San FranciscoSan Francisco, California  94115
Kaiser Permanente-Santa Teresa-San JoseSan Jose, California  95119
Kaiser Permanente-San RafaelSan Rafael, California  94903
Kaiser Permanente-Santa RosaSanta Rosa, California  95403
Kaiser Permanente-South San FranciscoSouth San Francisco, California  94080
Kaiser Permanente-StocktonStockton, California  95210
Kaiser Permanente-VallejoVallejo, California  94589
Kaiser Permanente-Walnut CreekWalnut Creek, California  94596
Oncare Hawaii Inc-POB IIHonolulu, Hawaii  96813
Oncare Hawaii Inc-KuakiniHonolulu, Hawaii  96817
University of HawaiiHonolulu, Hawaii  96813
Saint Francis Hospital and Health CentersBeech Grove, Indiana  46107
Reid Hospital and Health Care ServicesRichmond, Indiana  47374
Cancer Center of Kansas-KingmanKingman, Kansas  67068
Cancer Center of Kansas - ParsonsParsons, Kansas  67357
Cancer Center of Kansas - PrattPratt, Kansas  67124
Cancer Center of Kansas-Wichita Medical Arts TowerWichita, Kansas  67208
Cancer Center of Kansas - Main OfficeWichita, Kansas  67214
DeSoto Regional Health SystemMansfield, Louisiana  71052
Louisiana State University Sciences Center- MonroeMonroe, Louisiana  71210
Highland ClinicShreveport, Louisiana  71105
Grand Rapids Clinical Oncology ProgramGrand Rapids, Michigan  49503
Saint Mary's Health CareGrand Rapids, Michigan  49503
Spectrum Health at Butterworth CampusGrand Rapids, Michigan  49503
Mercy Health Partners-Mercy CampusMuskegon, Michigan  49443
Saint Luke's Hospital of Kansas CityKansas City, Missouri  64111
Saint Joseph Health CenterKansas City, Missouri  64114
Liberty Radiation Oncology ClinicKansas City, Missouri  64116
Hematology-Oncology Centers of the Northern Rockies PCBillings, Montana  59101
Saint Vincent HealthcareBillings, Montana  59101
Billings ClinicBillings, Montana  59107-7000
Saint James Community Hospital and Cancer Treatment CenterButte, Montana  59701
Benefis Healthcare- Sletten Cancer InstituteGreat Falls, Montana  59405
Saint Peter's Community HospitalHelena, Montana  59601
Glacier Oncology PLLCKalispell, Montana  59901
Saint Patrick Hospital - Community HospitalMissoula, Montana  59802
Interlakes Foundation Inc-RochesterRochester, New York  14623
Wayne Memorial HospitalGoldsboro, North Carolina  27534
Margaret R Pardee Memorial HospitalHendersonville, North Carolina  28791
Doctors HospitalColumbus, Ohio  43228
Grant Medical CenterColumbus, Ohio  43215
Mount Carmel Health Center WestColumbus, Ohio  43222
Good Samaritan Hospital - DaytonDayton, Ohio  45406
Dayton CCOPDayton, Ohio  45429
Samaritan North Health CenterDayton, Ohio  45415
Blanchard Valley HospitalFindlay, Ohio  45840
Atrium Medical Center-Middletown Regional HospitalFranklin, Ohio  45005-1066
Kettering Medical CenterKettering, Ohio  45429
Marietta Memorial HospitalMarietta, Ohio  45750
Upper Valley Medical CenterTroy, Ohio  45373
Saint Ann's HospitalWesterville, Ohio  43081
Genesis HealthCare SystemZanesville, Ohio  43701
AnMed Health HospitalAnderson, South Carolina  29621
Upstate Carolina CCOPSpartanburg, South Carolina  29303
Harrison Bremerton Hematology and OncologyBremerton, Washington  98310
Columbia Basin Hematology and Oncology PLLCKennewick, Washington  99336
Minor and James Medical PLLCSeattle, Washington  98104
The PolyclinicSeattle, Washington  98122
Swedish Medical Center-First HillSeattle, Washington  98122-4307
Lahey Clinic Medical CenterBurlington, Massachusetts  01805
Delnor Community HospitalGeneva, Illinois  60134
Cancer Center of Kansas-LiberalLiberal, Kansas  67901
Skagit Valley HospitalMt. Vernon, Washington  98273
Evergreen Hematology and Oncology PSSpokane, Washington  99218
Arizona Cancer Center at University Medical Center NorthTucson, Arizona  85719
Kuakini Medical CenterHonolulu, Hawaii  96817
Arizona Cancer Center at UMC Orange GroveTucson, Arizona  85704
Kaiser Permanente-Deer Valley Medical CenterAntioch, California  94531
Kaiser Permanente Medical Center-VacavilleVacaville, California  95688
Kaiser Permanente Moanalua Medical CenterHonolulu, Hawaii  96819
Wilcox Memorial Hospital and Kauai Medical ClinicLihue, Hawaii  96766-1099
Central DuPage Hospital Cancer CenterWarrenville, Illinois  60555
Saint Luke's South HospitalOverland Park, Kansas  66213
Kansas City CCOPPrairie Village, Kansas  66208
Spectrum Health Reed City HospitalReed City, Michigan  49677
Heartland Hematology and Oncology Associates IncorporatedKansas City, Missouri  64118
Arnot Ogden Medical CenterElmira, New York  14905
Southern Ohio Medical CenterPortsmouth, Ohio  45662
Saint Charles Medical Center-BendBend, Oregon  97701
Saint Francis HospitalGreenville, South Carolina  29601
Cancer Care Center at Island HospitalAnacortes, Washington  98221
Highline Medical Center-Main CampusBurien, Washington  98166
United General HospitalSedro-Woolley, Washington  98284
Swedish Cancer Institute-IssaquahIssaquah, Washington  98029
Franciscan St. Francis HealthIndianapolis, Indiana  46237
Southwest Oncology GroupSan Antonio, Texas  78245
PeaceHealth Saint Joseph Medical CenterBellingham, Washington  98225
Bronson Battle CreekBattle Creek, Michigan  49017
Springfield Regional Medical CenterSpringfield, Ohio  45505
NEA Baptist Memorial HospitalJonesboro, Arkansas  72401
Harrison Poulsbo Hematology and OncologyPoulsbo, Washington  98370
Christus Saint Frances Cabrini HospitalAlexandria, Louisiana  71301
Overton Brooks Veteran's Administration Medical CenterShreveport, Louisiana  71101
Park Ridge Hospital Breast Health CenterHendersonville, North Carolina  28792
NEA Baptist Clinic-MatthewsJonesboro, Arkansas  72401
OnCare Hawaii-LilihaHonolulu, Hawaii  96817-3169
Oncare Hawaii Inc - Kapiolani Medical Center at Pali MomiAiea, Hawaii  96701