PXD101 in Treating Patients With Relapsed or Refractory Aggressive B-Cell Non-Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00303953
First received: March 15, 2006
Last updated: April 23, 2014
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Drug: belinostat
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of PXD101 (NSC-726630) in Relapsed and Refractory Aggressive B-Cell Lymphomas

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Assess Number of Patients Who Achieve Confirmed and Unconfirmed Complete Response (CR) or Partial Response (PR) [ Time Frame: assessed at week 8, and every 3 months for 3 years ] [ Designated as safety issue: No ]
    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. CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. Partial Response(PR) is a 50% decrease in the 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.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: assessed every 3 months for 3 years ] [ Designated as safety issue: No ]
    Measured from time of registration to death, or last contact date

  • Progression-free Survival [ Time Frame: assessed at week 8, then every 3 months for 3 years ] [ Designated as safety issue: No ]
    Measured from date of registration to time of first documentation of progression or death, or last contact date. Progression is defined as a 50% increase in sum of products of greatest diameters (SPD) of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline; appearance of a new lesion/site; unequivocal progression of non-measurable disease in the opinion of the treating physician; death due to disease without prior documentation of progression.


Enrollment: 22
Study Start Date: January 2006
Study Completion Date: August 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I

Patients will receive an infusion of PXD101 once a day for 5 days. Treatment may repeat every 3 weeks for up to 2 years. Some patients will also undergo core biopsy and blood collection for laboratory studies before and after treatment.

After finishing treatment, patients will be evaluated every 3-6 months for up to 3 years.

Drug: belinostat
Given IV
Other Name: PXD101

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00303953

  Hide Study Locations
Locations
United States, Alabama
Providence Hospital
Mobile, Alabama, United States, 36608
United States, Arizona
University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724
United States, Arkansas
NEA Baptist Memorial Hospital
Jonesboro, Arkansas, United States, 72401
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Valley Medical Oncology Consultants-Castro Valley
Castro Valley, California, United States, 94546
East Bay Radiation Oncology Center
Castro Valley, California, United States, 94546
Eden Hospital Medical Center
Castro Valley, California, United States, 94546
Valley Medical Oncology Consultants-Fremont
Fremont, California, United States, 94538
Marin General Hospital
Greenbrae, California, United States, 94904
Saint Rose Hospital
Hayward, California, United States, 94545
Contra Costa Regional Medical Center
Martinez, California, United States, 94553-3156
Bay Area Breast Surgeons Inc
Oakland, California, United States, 94609
Larry G Strieff MD Medical Corporation
Oakland, California, United States, 94609
Bay Area Tumor Institute CCOP
Oakland, California, United States, 94609
Alta Bates Summit Medical Center - Summit Campus
Oakland, California, United States, 94609
Highland General Hospital
Oakland, California, United States, 94602
Tom K Lee Inc
Oakland, California, United States, 94609
Valley Care Health System - Pleasanton
Pleasanton, California, United States, 94588
Valley Medical Oncology Consultants
Pleasanton, California, United States, 94588
Doctors Medical Center- JC Robinson Regional Cancer Center
San Pablo, California, United States, 94806
Sutter Solano Medical Center
Vallejo, California, United States, 94589
United States, Florida
Cancer Centers of Central Florida PA
Leesburg, Florida, United States, 34788
United States, Illinois
Decatur Memorial Hospital
Decatur, Illinois, United States, 62526
Advocate Sherman Hospital
Elgin, Illinois, United States, 60123
Loyola University Medical Center
Maywood, Illinois, United States, 60153
Memorial Medical Center
Springfield, Illinois, United States, 62781-0001
United States, Indiana
Saint Francis Hospital and Health Centers
Beech Grove, Indiana, United States, 46107
Reid Hospital and Health Care Services
Richmond, Indiana, United States, 47374
United States, Kansas
Providence Medical Center
Kansas City, Kansas, United States, 66112
Lawrence Memorial Hospital
Lawrence, Kansas, United States, 66044
Menorah Medical Center
Overland Park, Kansas, United States, 66209
Radiation Oncology Practice Corporation Southwest
Overland Park, Kansas, United States, 66210
Salina Regional Health Center
Salina, Kansas, United States, 67401
Shawnee Mission Medical Center
Shawnee Mission, Kansas, United States, 66204
United States, Louisiana
Baton Rouge General Medical Center
Baton Rouge, Louisiana, United States, 70806
Mary Bird Perkins Cancer Center
Baton Rouge, Louisiana, United States, 70809
DeSoto Regional Health System
Mansfield, Louisiana, United States, 71052
Louisiana State University Sciences Center- Monroe
Monroe, Louisiana, United States, 71210
Interim LSU Public Hospital
New Orleans, Louisiana, United States, 70112
Louisiana State University Health Science Center
New Orleans, Louisiana, United States, 70112
Louisiana State University Health Sciences Center Shreveport
Shreveport, Louisiana, United States, 71130
Highland Clinic
Shreveport, Louisiana, United States, 71105
United States, Massachusetts
Boston Medical Center
Boston, Massachusetts, United States, 02118
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, Missouri
Centerpoint Medical Center LLC
Independence, Missouri, United States, 64057
Truman Medical Center
Kansas City, Missouri, United States, 64108
North Kansas City Hospital
Kansas City, Missouri, United States, 64116
Radiation Oncology Practice Corporation - North
Kansas City, Missouri, United States, 64154
Radiation Oncology Practice Corporation South
Kansas City, Missouri, United States, 64114
Research Medical Center
Kansas City, Missouri, United States, 64132
Saint Joseph Health Center
Kansas City, Missouri, United States, 64114
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, United States, 64111
Saint Luke's Cancer Institute
Kansas City, Missouri, United States, 64111
Liberty Hospital
Liberty, Missouri, United States, 64068
Heartland Regional Medical Center
Saint Joseph, Missouri, United States, 64506
United States, Montana
Hematology-Oncology Centers of the Northern Rockies PC
Billings, Montana, United States, 59102
Billings Clinic
Billings, Montana, United States, 59107-7000
Deaconess Medical Center
Billings, Montana, United States, 59107
Northern Rockies Radiation Oncology Center
Billings, Montana, United States, 59101
Saint Vincent Healthcare
Billings, Montana, United States, 59101
Montana Cancer Consortium CCOP
Billings, Montana, United States, 59101
Bozeman Deaconess Cancer Center
Bozeman, Montana, United States, 59715
Bozeman Deaconess Hospital
Bozeman, Montana, United States, 59715
Internal Medicine of Bozeman
Bozeman, Montana, United States, 59715
Saint James Community Hospital and Cancer Treatment Center
Butte, Montana, United States, 59701
Great Falls Clinic
Great Falls, Montana, United States, 59405
Berdeaux, Donald MD (UIA Investigator)
Great Falls, Montana, United States, 59405
Northern Montana Hospital
Havre, Montana, United States, 59501
Saint Peter's Community Hospital
Helena, Montana, United States, 59601
Kalispell Medical Oncology
Kalispell, Montana, United States, 59901
Kalispell Regional Medical Center
Kalispell, Montana, United States, 59901
Glacier Oncology PLLC
Kalispell, Montana, United States, 59901
Guardian Oncology and Center for Wellness
Missoula, Montana, United States, 59804
Saint Patrick Hospital - Community Hospital
Missoula, Montana, United States, 59802
Montana Cancer Specialists
Missoula, Montana, United States, 59802
Community Medical Hospital
Missoula, Montana, United States, 59801
United States, New York
Highland Hospital
Rochester, New York, United States, 14620
United States, North Carolina
Wayne Radiation Oncology
Goldsboro, North Carolina, United States, 27534
Wilson Medical Center
Wilson, North Carolina, United States, 27893
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267
Samaritan North Health Center
Dayton, Ohio, United States, 45415
Veteran Affairs Medical Center
Dayton, Ohio, United States, 45428
Miami Valley Hospital
Dayton, Ohio, United States, 45409
Good Samaritan Hospital - Dayton
Dayton, Ohio, United States, 45406
Grandview Hospital
Dayton, Ohio, United States, 45405
Dayton CCOP
Dayton, Ohio, United States, 45420
Blanchard Valley Hospital
Findlay, Ohio, United States, 45840
Atrium Medical Center-Middletown Regional Hospital
Franklin, Ohio, United States, 45005-1066
Kettering Medical Center
Kettering, Ohio, United States, 45429
Upper Valley Medical Center
Troy, Ohio, United States, 45373
Clinton Memorial Hospital
Wilmington, Ohio, United States, 45177
Greene Memorial Hospital
Xenia, Ohio, United States, 45385
United States, South Carolina
McLeod Regional Medical Center
Florence, South Carolina, United States, 29506
United States, Texas
Brooke Army Medical Center
Fort Sam Houston, Texas, United States, 78234
Wilford Hall Medical Center
Lackland AFB, Texas, United States, 78236
Southwest Oncology Group
San Antonio, Texas, United States, 78245
United States, Utah
American Fork Hospital
American Fork, Utah, United States, 84003
Sandra L Maxwell Cancer Center
Cedar City, Utah, United States, 84720
Logan Regional Hospital
Logan, Utah, United States, 84321
Cottonwood Hospital Medical Center
Murray, Utah, United States, 84107
Intermountain Medical Center
Murray, Utah, United States, 84157
McKay-Dee Hospital Center
Ogden, Utah, United States, 84403
Utah Valley Regional Medical Center
Provo, Utah, United States, 84604-3337
Dixie Medical Center Regional Cancer Center
Saint George, Utah, United States, 84770
LDS Hospital
Salt Lake City, Utah, United States, 84143
Utah Cancer Specialists-Salt Lake City
Salt Lake City, Utah, United States, 84106
Intermountain Health Care
Salt Lake City, Utah, United States, 84103
United States, Washington
PeaceHealth Saint Joseph Medical Center
Bellingham, Washington, United States, 98225
Harrison HealthPartners Hematology and Oncology-Bremerton
Bremerton, Washington, United States, 98310
Columbia Basin Hematology and Oncology PLLC
Kennewick, Washington, United States, 99336
Skagit Valley Hospital
Mount Vernon, Washington, United States, 98274
Harborview Medical Center
Seattle, Washington, United States, 98104
Group Health Cooperative-Seattle
Seattle, Washington, United States, 98112
Minor and James Medical PLLC
Seattle, Washington, United States, 98104
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Swedish Medical Center-First Hill
Seattle, Washington, United States, 98122-4307
University of Washington Medical Center
Seattle, Washington, United States, 98195
The Polyclinic
Seattle, Washington, United States, 98122
United General Hospital
Sedro-Woolley, Washington, United States, 98284
Cancer Care Northwest - Spokane South
Spokane, Washington, United States, 99202
Madigan Army Medical Center
Tacoma, Washington, United States, 98431
Wenatchee Valley Medical Center
Wenatchee, Washington, United States, 98801
United States, Wyoming
Welch Cancer Center
Sheridan, Wyoming, United States, 82801
Sponsors and Collaborators
Investigators
Principal Investigator: Steven Bernstein Southwest Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00303953     History of Changes
Other Study ID Numbers: NCI-2009-01096, NCI-2009-01096, CDR0000462614, S0520, S0520, U10CA032102
Study First Received: March 15, 2006
Results First Received: February 28, 2012
Last Updated: April 23, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Burkitt Lymphoma
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Experimental
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Belinostat
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2014