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): Providence Hospital
🇺🇸
Mobile, Alabama, United States
University of Arizona Health Sciences Center
🇺🇸
Tucson, Arizona, United States
NEA Baptist Memorial Hospital
🇺🇸
Jonesboro, Arkansas, United States
University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, 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
Valley Medical Oncology Consultants-Fremont
🇺🇸
Fremont, California, United States
Marin General Hospital
🇺🇸
Greenbrae, California, United States
Saint Rose Hospital
🇺🇸
Hayward, California, United States
Scroll for more (113 remaining)
Providence Hospital
🇺🇸Mobile, Alabama, United States