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

Phase 2

Completed

Conditions: Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma

Interventions: Drug: belinostat

Registration Number: NCT00303953

Lead Sponsor: National Cancer Institute (NCI)

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 22

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	belinostat	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.

Primary Outcome Measures

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

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

Trial Locations

Locations (123): Heartland Regional Medical Center
🇺🇸
Saint Joseph, Missouri, United States
Kalispell Medical Oncology
🇺🇸
Kalispell, Montana, United States
Kalispell Regional Medical Center
🇺🇸
Kalispell, Montana, United States
Guardian Oncology and Center for Wellness
🇺🇸
Missoula, Montana, United States
Boston Medical Center
🇺🇸
Boston, Massachusetts, United States
Harborview Medical Center
🇺🇸
Seattle, Washington, United States
Minor and James Medical PLLC
🇺🇸
Seattle, Washington, United States
University of Washington Medical Center
🇺🇸
Seattle, Washington, United States
University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
DeSoto Regional Health System
🇺🇸
Mansfield, Louisiana, United States
Saint Vincent Healthcare
🇺🇸
Billings, Montana, United States
Billings Clinic
🇺🇸
Billings, Montana, United States
Berdeaux, Donald MD (UIA Investigator)
🇺🇸
Great Falls, Montana, United States
Community Medical Hospital
🇺🇸
Missoula, Montana, United States
Saint Patrick Hospital - Community Hospital
🇺🇸
Missoula, Montana, United States
University of Cincinnati
🇺🇸
Cincinnati, Ohio, United States
Intermountain Health Care
🇺🇸
Salt Lake City, Utah, United States
Utah Cancer Specialists-Salt Lake City
🇺🇸
Salt Lake City, Utah, United States
LDS Hospital
🇺🇸
Salt Lake City, Utah, United States
Radiation Oncology Practice Corporation Southwest
🇺🇸
Overland Park, Kansas, United States
Shawnee Mission Medical Center
🇺🇸
Shawnee Mission, Kansas, United States
Welch Cancer Center
🇺🇸
Sheridan, Wyoming, United States
Menorah Medical Center
🇺🇸
Overland Park, Kansas, United States
Providence Medical Center
🇺🇸
Kansas City, Kansas, United States
Dayton CCOP
🇺🇸
Dayton, Ohio, United States
Providence Hospital
🇺🇸
Mobile, Alabama, United States
NEA Baptist Memorial Hospital
🇺🇸
Jonesboro, Arkansas, United States
Eden Hospital Medical Center
🇺🇸
Castro Valley, California, United States
University of Arizona Health Sciences Center
🇺🇸
Tucson, Arizona, United States
Montana Cancer Specialists
🇺🇸
Missoula, Montana, United States
East Bay Radiation Oncology Center
🇺🇸
Castro Valley, California, United States
Grandview Hospital
🇺🇸
Dayton, Ohio, United States
Bay Area Tumor Institute CCOP
🇺🇸
Oakland, California, United States
Bozeman Deaconess Cancer Center
🇺🇸
Bozeman, Montana, United States
Saint Rose Hospital
🇺🇸
Hayward, California, United States
Doctors Medical Center- JC Robinson Regional Cancer Center
🇺🇸
San Pablo, California, United States
Sutter Solano Medical Center
🇺🇸
Vallejo, California, United States
Larry G Strieff MD Medical Corporation
🇺🇸
Oakland, California, United States
Tom K Lee Inc
🇺🇸
Oakland, California, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
Glacier Oncology PLLC
🇺🇸
Kalispell, Montana, United States
Wilson Medical Center
🇺🇸
Wilson, North Carolina, United States
McLeod Regional Medical Center
🇺🇸
Florence, South Carolina, United States
Logan Regional Hospital
🇺🇸
Logan, Utah, United States
United General Hospital
🇺🇸
Sedro-Woolley, Washington, United States
Brooke Army Medical Center
🇺🇸
Fort Sam Houston, Texas, United States
Contra Costa Regional Medical Center
🇺🇸
Martinez, California, United States
Valley Medical Oncology Consultants-Fremont
🇺🇸
Fremont, California, United States
Advocate Sherman Hospital
🇺🇸
Elgin, Illinois, United States
Marin General Hospital
🇺🇸
Greenbrae, California, United States
Decatur Memorial Hospital
🇺🇸
Decatur, Illinois, United States
Good Samaritan Hospital - Dayton
🇺🇸
Dayton, Ohio, United States
Baton Rouge General Medical Center
🇺🇸
Baton Rouge, Louisiana, United States
Miami Valley Hospital
🇺🇸
Dayton, Ohio, United States
Mary Bird Perkins Cancer Center
🇺🇸
Baton Rouge, Louisiana, United States
Samaritan North Health Center
🇺🇸
Dayton, Ohio, United States
Internal Medicine of Bozeman
🇺🇸
Bozeman, Montana, United States
Northern Montana Hospital
🇺🇸
Havre, Montana, United States
Saint James Community Hospital and Cancer Treatment Center
🇺🇸
Butte, Montana, United States
Saint Luke's Cancer Institute
🇺🇸
Kansas City, Missouri, United States
Highland Hospital
🇺🇸
Rochester, New York, United States
Deaconess Medical Center
🇺🇸
Billings, Montana, United States
Saint Peter's Community Hospital
🇺🇸
Helena, Montana, United States
Wayne Radiation Oncology
🇺🇸
Goldsboro, North Carolina, United States
Great Falls Clinic
🇺🇸
Great Falls, Montana, United States
Atrium Medical Center-Middletown Regional Hospital
🇺🇸
Franklin, Ohio, United States
The Polyclinic
🇺🇸
Seattle, Washington, United States
Hematology-Oncology Centers of the Northern Rockies PC
🇺🇸
Billings, Montana, United States
Columbia Basin Hematology and Oncology PLLC
🇺🇸
Kennewick, Washington, United States
Clinton Memorial Hospital
🇺🇸
Wilmington, Ohio, United States
Sandra L Maxwell Cancer Center
🇺🇸
Cedar City, Utah, United States
Skagit Valley Hospital
🇺🇸
Mount Vernon, Washington, United States
McKay-Dee Hospital Center
🇺🇸
Ogden, Utah, United States
Swedish Medical Center-First Hill
🇺🇸
Seattle, Washington, United States
Southwest Oncology Group
🇺🇸
San Antonio, Texas, United States
Intermountain Medical Center
🇺🇸
Murray, Utah, United States
American Fork Hospital
🇺🇸
American Fork, Utah, United States
Wilford Hall Medical Center
🇺🇸
Lackland AFB, Texas, United States
Blanchard Valley Hospital
🇺🇸
Findlay, Ohio, United States
Upper Valley Medical Center
🇺🇸
Troy, Ohio, United States
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
🇺🇸
Seattle, Washington, United States
Cottonwood Hospital Medical Center
🇺🇸
Murray, Utah, United States
Dixie Medical Center Regional Cancer Center
🇺🇸
Saint George, Utah, United States
Kettering Medical Center
🇺🇸
Kettering, Ohio, United States
Wenatchee Valley Medical Center
🇺🇸
Wenatchee, Washington, United States
Madigan Army Medical Center
🇺🇸
Tacoma, Washington, United States
Utah Valley Regional Medical Center
🇺🇸
Provo, Utah, United States
Cancer Care Northwest - Spokane South
🇺🇸
Spokane, Washington, United States
Highland General Hospital
🇺🇸
Oakland, California, United States
Greene Memorial Hospital
🇺🇸
Xenia, Ohio, United States
Alta Bates Summit Medical Center - Summit Campus
🇺🇸
Oakland, California, United States
Group Health Cooperative-Seattle
🇺🇸
Seattle, Washington, United States
Bay Area Breast Surgeons Inc
🇺🇸
Oakland, California, United States
Valley Medical Oncology Consultants-Castro Valley
🇺🇸
Castro Valley, California, United States
Valley Medical Oncology Consultants
🇺🇸
Pleasanton, California, United States
Valley Care Health System - Pleasanton
🇺🇸
Pleasanton, California, United States
Cancer Centers of Central Florida PA
🇺🇸
Leesburg, Florida, United States
Saint Francis Hospital and Health Centers
🇺🇸
Beech Grove, Indiana, United States
Memorial Medical Center
🇺🇸
Springfield, Illinois, United States
Reid Hospital and Health Care Services
🇺🇸
Richmond, Indiana, United States
Lawrence Memorial Hospital
🇺🇸
Lawrence, Kansas, United States
Salina Regional Health Center
🇺🇸
Salina, Kansas, United States
Interim LSU Public Hospital
🇺🇸
New Orleans, Louisiana, United States
Louisiana State University Sciences Center- Monroe
🇺🇸
Monroe, Louisiana, United States
Louisiana State University Health Science Center
🇺🇸
New Orleans, Louisiana, United States
Highland Clinic
🇺🇸
Shreveport, Louisiana, United States
Louisiana State University Health Sciences Center Shreveport
🇺🇸
Shreveport, Louisiana, United States
Truman Medical Center
🇺🇸
Kansas City, Missouri, United States
Centerpoint Medical Center LLC
🇺🇸
Independence, Missouri, United States
Saint Luke's Hospital of Kansas City
🇺🇸
Kansas City, Missouri, United States
Saint Joseph Health Center
🇺🇸
Kansas City, Missouri, United States
North Kansas City Hospital
🇺🇸
Kansas City, Missouri, United States
Research Medical Center
🇺🇸
Kansas City, Missouri, United States
Liberty Hospital
🇺🇸
Liberty, Missouri, United States
Radiation Oncology Practice Corporation - North
🇺🇸
Kansas City, Missouri, United States
Northern Rockies Radiation Oncology Center
🇺🇸
Billings, Montana, United States
Montana Cancer Consortium CCOP
🇺🇸
Billings, Montana, United States
Henry Ford Hospital
🇺🇸
Detroit, Michigan, United States
Radiation Oncology Practice Corporation South
🇺🇸
Kansas City, Missouri, United States
Veteran Affairs Medical Center
🇺🇸
Dayton, Ohio, United States
PeaceHealth Saint Joseph Medical Center
🇺🇸
Bellingham, Washington, United States
Harrison HealthPartners Hematology and Oncology-Bremerton
🇺🇸
Bremerton, Washington, United States
Bozeman Deaconess Hospital
🇺🇸
Bozeman, Montana, United States