Clinical trial NCT00303953: PXD101 in Treating Patients With Relapsed or Refractory Aggressive B-Cell Non-Hodgkin's Lymphoma
Official title: Phase II Study of PXD101 (NSC-726630) in Relapsed and Refractory Aggressive B-Cell Lymphomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-03-17
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial is studying how well PXD101 works in treating patients with relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. PXD101 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.

Detailed description: PRIMARY OBJECTIVES:

I. Evaluate response rate in patients with relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma treated with PXD101.

SECONDARY OBJECTIVES:

I. Determine the toxicity of this drug in these patients. II. Estimate the 6-month progression-free survival rate in patients treated with this drug.

TERTIARY OBJECTIVES:

I. Determine the major histocompatability complex of class II proteins (HLA-DR, -DP, -DQ), TUNEL, and CD8 infiltration status, by immunochemistry on paired pre- and post-treatment tumor samples, in the first 20 patients enrolled.

II. Measure CIITA and HLA-DR mRNA expression using quantitative reverse transcriptase-polymerase chain reaction and determine, preliminarily, the associations of these markers with progression-free survival.

III. Evaluate paired pre- and post-treatment peripheral blood mononuclear cells from patients for histone acetylation status and determine correlation with findings from duplicate experiments on pre- and post-needle core biopsies.

OUTLINE: This is a multicenter study.

Patients receive PXD101 IV over 30 minutes on days 1-5. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Needle core biopsies and peripheral blood mononuclear cells are obtained from the first 20 patients pre- and post-treatment for biomarker correlative studies.

After completion of study treatment, patients are followed every 3-6 months for up to 3 years.

Eligibility criteria: Inclusion Criteria:

* Biopsy-proven (no needle aspirations or cytologies) aggressive B-cell non-Hodgkin's lymphoma (NHL), including 1 of the following histology subtypes:

  * Diffuse large cell NHL
  * Burkitt's or Burkitt-like NHL
  * Primary mediastinal NHL
* Relapsed or refractory disease
* Bidimensionally measurable disease
* Transformed NHL allowed
* Not eligible for stem cell transplantation (for patients registered to study at first relapse)
* No active CNS involvement by lymphoma
* Zubrod performance status 0-2
* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to PXD101
* Absolute neutrophil count \>= 1,500/mm\^3
* Platelet count\>=100,000/mm\^3
* WBC \>= 3,000/mm\^3
* Creatinine \< 2 times upper limit of normal (ULN) OR creatinine clearance \>= 60 mL/min
* No significant EKG abnormalities
* Bilirubin normal
* SGOT/SGPT \< 2.5 times ULN (=\< 5 times ULN if liver involvement)
* No long QT syndrome or marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of QTc interval \> 500 msec)
* No other significant cardiovascular disease, including any of the following:

  * Unstable angina pectoris
  * Uncontrolled hypertension
  * Congestive heart failure related to primary cardiac disease
  * Any condition requiring anti-arrhythmic therapy
  * Ischemic or severe valvular heart disease
  * Myocardial infarction within the past 6 months
* No major surgery within 28 days prior to study entry
* No concurrent combination antiretroviral therapy for HIV-positive patients
* No concurrent medication that may cause Torsades de Pointes (i.e., prolongation of the QT interval \> 500 msec)
* At least 14 days since prior radiotherapy
* At least 2 weeks since prior valproic acid or any other histone deacetylase inhibitor
* No clinical evidence of any of the following:

  * Severe peripheral vascular disease
  * Diabetic ulcers or venous stasis ulcers
  * History of deep venous or arterial thrombosis within the past 3 months
* Radioimmunotherapy is considered a chemotherapy regimen
* Single-agent rituximab is not considered a chemotherapy regimen
* Standard salvage chemotherapy followed by autologous stem cell transplantation is considered 1 regimen
* No known AIDS or HIV-associated complex
* Not pregnant or nursing
* Fertile patients must use effective contraception
* No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or in situ carcinoma of the cervix
* At least 2 weeks since prior therapy and recovered
* No more than 5 prior chemotherapy regimens

Primary outcomes:
measure: Assess Number of Patients Who Achieve Confirmed and Unconfirmed Complete Response (CR) or Partial Response (PR)
timeFrame: assessed at week 8, and every 3 months for 3 years
Secondary outcomes:
measure: Overall Survival
timeFrame: assessed every 3 months for 3 years
measure: Progression-free Survival
timeFrame: assessed at week 8, then every 3 months for 3 years
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Providence Hospital
state: Alabama
city: Tucson
country: United States
facility: University of Arizona Health Sciences Center
state: Arizona
city: Jonesboro
country: United States
facility: NEA Baptist Memorial Hospital
state: Arkansas
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Castro Valley
country: United States
facility: East Bay Radiation Oncology Center
state: California
city: Castro Valley
country: United States
facility: Eden Hospital Medical Center
state: California
city: Castro Valley
country: United States
facility: Valley Medical Oncology Consultants-Castro Valley
state: California
city: Fremont
country: United States
facility: Valley Medical Oncology Consultants-Fremont
state: California
city: Greenbrae
country: United States
facility: Marin General Hospital
state: California
city: Hayward
country: United States
facility: Saint Rose Hospital
state: California
city: Martinez
country: United States
facility: Contra Costa Regional Medical Center
state: California
city: Oakland
country: United States
facility: Highland General Hospital
state: California
city: Oakland
country: United States
facility: Alta Bates Summit Medical Center - Summit Campus
state: California
city: Oakland
country: United States
facility: Bay Area Breast Surgeons Inc
state: California
city: Oakland
country: United States
facility: Bay Area Tumor Institute CCOP
state: California
city: Oakland
country: United States
facility: Larry G Strieff MD Medical Corporation
state: California
city: Oakland
country: United States
facility: Tom K Lee Inc
state: California
city: Pleasanton
country: United States
facility: Valley Care Health System - Pleasanton
state: California
city: Pleasanton
country: United States
facility: Valley Medical Oncology Consultants
state: California
city: San Pablo
country: United States
facility: Doctors Medical Center- JC Robinson Regional Cancer Center
state: California
city: Vallejo
country: United States
facility: Sutter Solano Medical Center
state: California
city: Leesburg
country: United States
facility: Cancer Centers of Central Florida PA
state: Florida
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Elgin
country: United States
facility: Advocate Sherman Hospital
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Springfield
country: United States
facility: Memorial Medical Center
state: Illinois
city: Beech Grove
country: United States
facility: Saint Francis Hospital and Health Centers
state: Indiana
city: Richmond
country: United States
facility: Reid Hospital and Health Care Services
state: Indiana
city: Kansas City
country: United States
facility: Providence Medical Center
state: Kansas
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Overland Park
country: United States
facility: Menorah Medical Center
state: Kansas
city: Overland Park
country: United States
facility: Radiation Oncology Practice Corporation Southwest
state: Kansas
city: Salina
country: United States
facility: Salina Regional Health Center
state: Kansas
city: Shawnee Mission
country: United States
facility: Shawnee Mission Medical Center
state: Kansas
city: Baton Rouge
country: United States
facility: Baton Rouge General Medical Center
state: Louisiana
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center
state: Louisiana
city: Mansfield
country: United States
facility: DeSoto Regional Health System
state: Louisiana
city: Monroe
country: United States
facility: Louisiana State University Sciences Center- Monroe
state: Louisiana
city: New Orleans
country: United States
facility: Interim LSU Public Hospital
state: Louisiana
city: New Orleans
country: United States
facility: Louisiana State University Health Science Center
state: Louisiana
city: Shreveport
country: United States
facility: Highland Clinic
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center Shreveport
state: Louisiana
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Independence
country: United States
facility: Centerpoint Medical Center LLC
state: Missouri
city: Kansas City
country: United States
facility: Truman Medical Center
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Kansas City
country: United States
facility: Radiation Oncology Practice Corporation South
state: Missouri
city: Kansas City
country: United States
facility: Saint Joseph Health Center
state: Missouri
city: Kansas City
country: United States
facility: North Kansas City Hospital
state: Missouri
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Kansas City
country: United States
facility: Radiation Oncology Practice Corporation - North
state: Missouri
city: Liberty
country: United States
facility: Liberty Hospital
state: Missouri
city: Saint Joseph
country: United States
facility: Heartland Regional Medical Center
state: Missouri
city: Billings
country: United States
facility: Montana Cancer Consortium CCOP
state: Montana
city: Billings
country: United States
facility: Northern Rockies Radiation Oncology Center
state: Montana
city: Billings
country: United States
facility: Saint Vincent Healthcare
state: Montana
city: Billings
country: United States
facility: Hematology-Oncology Centers of the Northern Rockies PC
state: Montana
city: Billings
country: United States
facility: Billings Clinic
state: Montana
city: Billings
country: United States
facility: Deaconess Medical Center
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Cancer Center
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Hospital
state: Montana
city: Bozeman
country: United States
facility: Internal Medicine of Bozeman
state: Montana
city: Butte
country: United States
facility: Saint James Community Hospital and Cancer Treatment Center
state: Montana
city: Great Falls
country: United States
facility: Berdeaux, Donald MD (UIA Investigator)
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic
state: Montana
city: Havre
country: United States
facility: Northern Montana Hospital
state: Montana
city: Helena
country: United States
facility: Saint Peter's Community Hospital
state: Montana
city: Kalispell
country: United States
facility: Glacier Oncology PLLC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Medical Oncology
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Community Medical Hospital
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Specialists
state: Montana
city: Missoula
country: United States
facility: Saint Patrick Hospital - Community Hospital
state: Montana
city: Missoula
country: United States
facility: Guardian Oncology and Center for Wellness
state: Montana
city: Rochester
country: United States
facility: Highland Hospital
state: New York
city: Goldsboro
country: United States
facility: Wayne Radiation Oncology
state: North Carolina
city: Wilson
country: United States
facility: Wilson Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Dayton
country: United States
facility: Grandview Hospital
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital - Dayton
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Health Center
state: Ohio
city: Dayton
country: United States
facility: Dayton CCOP
state: Ohio
city: Dayton
country: United States
facility: Veteran Affairs Medical Center
state: Ohio
city: Findlay
country: United States
facility: Blanchard Valley Hospital
state: Ohio
city: Franklin
country: United States
facility: Atrium Medical Center-Middletown Regional Hospital
state: Ohio
city: Kettering
country: United States
facility: Kettering Medical Center
state: Ohio
city: Troy
country: United States
facility: Upper Valley Medical Center
state: Ohio
city: Wilmington
country: United States
facility: Clinton Memorial Hospital
state: Ohio
city: Xenia
country: United States
facility: Greene Memorial Hospital
state: Ohio
city: Florence
country: United States
facility: McLeod Regional Medical Center
state: South Carolina
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Lackland AFB
country: United States
facility: Wilford Hall Medical Center
state: Texas
city: San Antonio
country: United States
facility: Southwest Oncology Group
state: Texas
city: American Fork
country: United States
facility: American Fork Hospital
state: Utah
city: Cedar City
country: United States
facility: Sandra L Maxwell Cancer Center
state: Utah
city: Logan
country: United States
facility: Logan Regional Hospital
state: Utah
city: Murray
country: United States
facility: Cottonwood Hospital Medical Center
state: Utah
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Ogden
country: United States
facility: McKay-Dee Hospital Center
state: Utah
city: Provo
country: United States
facility: Utah Valley Regional Medical Center
state: Utah
city: Saint George
country: United States
facility: Dixie Medical Center Regional Cancer Center
state: Utah
city: Salt Lake City
country: United States
facility: Intermountain Health Care
state: Utah
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists-Salt Lake City
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Bellingham
country: United States
facility: PeaceHealth Saint Joseph Medical Center
state: Washington
city: Bremerton
country: United States
facility: Harrison HealthPartners Hematology and Oncology-Bremerton
state: Washington
city: Kennewick
country: United States
facility: Columbia Basin Hematology and Oncology PLLC
state: Washington
city: Mount Vernon
country: United States
facility: Skagit Valley Hospital
state: Washington
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: Minor and James Medical PLLC
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
state: Washington
city: Seattle
country: United States
facility: Group Health Cooperative-Seattle
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center-First Hill
state: Washington
city: Seattle
country: United States
facility: The Polyclinic
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Sedro-Woolley
country: United States
facility: United General Hospital
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest - Spokane South
state: Washington
city: Tacoma
country: United States
facility: Madigan Army Medical Center
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Medical Center
state: Washington
city: Sheridan
country: United States
facility: Welch Cancer Center
state: Wyoming
Study officials:
affiliation: SWOG Cancer Research Network
name: Steven Bernstein
role: PRINCIPAL_INVESTIGATOR
References: