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

Phase II Study of PXD101 (NSC-726630) in Relapsed and Refractory Aggressive B-Cell Lymphomas

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma
• Intervention / Treatment: Drug: belinostat

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: PXD101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess Number of Patients Who Achieve Confirmed and Unconfirmed Complete Response (CR) or Partial Response (PR)	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.	assessed at week 8, and every 3 months for 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Measured from time of registration to death, or last contact date	assessed every 3 months for 3 years
Progression-free Survival	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.	assessed at week 8, then every 3 months for 3 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: March 15, 2006
• First Submitted That Met QC Criteria: March 15, 2006
• First Posted (Estimate): March 17, 2006

Study Record Updates

• Last Update Posted (Estimate): May 12, 2014
• Last Update Submitted That Met QC Criteria: April 23, 2014
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Infections; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Disease Attributes; DNA Virus Infections; Tumor Virus Infections; Epstein-Barr Virus Infections; Herpesviridae Infections; Lymphoma, B-Cell; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Recurrence; Burkitt Lymphoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Histone Deacetylase Inhibitors; Belinostat
• Other Study ID Numbers: NCI-2009-01096 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA032102 (U.S. NIH Grant/Contract); CDR0000462614; S0520 (Other Identifier: CTEP)