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

Recurrent Adult Diffuse Large Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00303953
• Other study ID #: NCI-2009-01096
• Secondary ID: NCI-2009-01096CD
• Status: Completed
• Phase: Phase 2
• First received: March 15, 2006
• Last updated: April 23, 2014
• Start date: January 2006
• Est. completion date: August 2010

Study information

• Verified date: April 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: August 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Burkitt Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Recurrent Adult Burkitt Lymphoma
• Recurrent Adult Diffuse Large Cell Lymphoma

Intervention

Drug:
• belinostat
Given IV

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Overall Survival	Measured from time of registration to death, or last contact date	assessed every 3 months for 3 years	No
Secondary	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	No