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A Phase II Exploratory Study of PXD-101(Belinostat) Followed by Zevalin in Patients With Relapsed Aggressive High-Risk Lymphoma (Stage 1)


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Anaplastic Large Cell Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Mantle Cell Lymphoma

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Trial Information

A Phase II Exploratory Study of PXD-101(Belinostat) Followed by Zevalin in Patients With Relapsed Aggressive High-Risk Lymphoma (Stage 1)


PRIMARY OBJECTIVES:

I. To document the complete response rate and overall response for patients with relapsed
aggressive high-risk non-Hodgkin's lymphoma treated with two cycles PXD-101 followed by one
cycle of Zevalin.

SECONDARY OBJECTIVES:

I. To estimate 2-year progression-free survival in patients with relapsed aggressive
high-risk non-Hodgkin's lymphoma treated with two cycles PXD-101 followed by one cycle of
Zevalin.

II. To evaluate the toxicity of two cycles PXD-101 and one cycle of Zevalin in patients with
relapsed aggressive high-risk non-Hodgkin's lymphoma.

OUTLINE:

Patients receive belinostat intravenously (IV) over 30-60 minutes on days 1-5. Treatment
with belinostat repeats every 21 days for 2 courses. Patients then receive rituximab IV on
days 1 and either 7, 8, or 9, and yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on
day 50. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and
then every 6 months for 3 years.


Inclusion Criteria:



- Patients must have biopsy confirmed, cluster of differentiation (CD)20 positive
diffuse large B-cell lymphoma, mantel cell, high grade-B-cell or anaplastic large B
cell non-Hodgkin lymphoma (NHL); AND bone marrow must show =< 20% CD20+ B-cells with
>= 15% cellularity within 42 days of study registration

- Any stage disease is allowed

- Patients must have been previously treated:

- >= 3rd line if bone marrow transplant (BMT) candidate OR

- >= 2nd line if not BMT candidate OR

- >= 2nd relapse for BMT candidate OR

- >= 1st relapse for non- BMT candidate

- Patients must have a diagnostic quality contrast computed tomography (CT) scan of the
chest, abdomen and pelvis OR baseline positron emission tomography (PET)-CT scan
performed within 28 days prior to registration

- All patients must have bidimensionally measurable disease with lesions at least 1.5
cm in one dimension all measurable disease must be assessed within 28 days of
registration

- For purposes of determining prior drug regimens the following should be used as a
standard; radiation therapy counts as 1 treatment, BMT including induction counts as
one treatment, radioimmunotherapy is not considered a chemotherapy regimen, rituximab
alone is not considered a treatment; all prior therapy must have been completed at
least 30 days prior to registration; patients should not have taken valproic acid, or
any other histone deacetylase inhibitor (eg., vorinostat, romidepsin), for at least
30 days prior to registration; patients must have recovered from any toxicities
related to therapies prior to registration

- Patients must not have clinical evidence of central nervous system involvement by
lymphoma, since proposed treatment would not be able to address it adequately; any
laboratory (eg., lactate dehydrogenase [LDH]) or radiographic tests performed to
access central nervous system (CNS) involvement must be negative and must be
performed within 42 days prior to registration

- Patients must have unilateral or bilateral bone marrow biopsy performed within 42
days prior to registration

- Life expectancy of greater than 3 months

- Karnofsky performance status >= 60%

- Leukocytes >= 3,000/mcL

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])
=< 2.5 X institutional upper limit of normal

- Total bilirubin =< 1.5 X institutional upper limit of normal (unless associated with
Gilbert's syndrome)

- Serum creatinine < 2 x institutional upper limit of normal OR

- Measured creatinine clearance >= 60 mL/min

- LDH < 1.50 X institutional upper limit of normal

- Patients must have an electrocardiogram (EKG) with no significant abnormalities
within 28 days prior to registration

- The effects of PXD-101 on the developing human fetus at the recommended therapeutic
dose are unknown; for this reason women of child-bearing potential and men must agree
to use adequate contraception (hormonal or barrier method of birth control;
abstinence) prior to study entry and for the duration of study participation; should
a woman become pregnant or suspect she is pregnant while she or her partner is
participating in this study, the patient should inform the treating physician
immediately

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 30 days (6 weeks for
nitrosoureas or mitomycin C) prior to study screening or those who have not recovered
from adverse events due to agents administered more than 4 weeks earlier

- Prior radioimmunotherapy

- Pregnant or nursing

- Clinical evidence of CNS involvement by lymphoma

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to PXD-101 or Zevalin or other agents used in the study

- Concomitant medication that may cause Torsade de Pointes, i.e. prolongation of the QT
interval > 500 msec

- Significant cardiovascular disease including unstable angina pectoris, uncontrolled
hypertension, congestive heart failure related to primary cardiac disease, any
condition requiring anti-arrhythmic therapy, ischemic or valvular heart disease, or a
myocardial infarction within the past 6 months

- Current long QT syndrome or baseline prolongation of QT/QTcF interval, i.e.
demonstration of a QTcF interval > 450 msec

- Clinical evidence of severe peripheral vascular disease, diabetic ulcers or venous
stasis ulcers, or history of deep venous or arterial thrombosis within 3 months prior
to screening

- Known to be human immunodeficiency virus (HIV) positive or with known acquired
immunodeficiency syndrome (AIDS) syndrome

- Patients may not be receiving any other investigational agents

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Complete response rate

Outcome Time Frame:

Up to 5 years

Safety Issue:

No

Principal Investigator

Thomas Miller

Investigator Role:

Principal Investigator

Investigator Affiliation:

Arizona Cancer Center - Tucson

Authority:

United States: Food and Drug Administration

Study ID:

12-0288-04

NCT ID:

NCT01686165

Start Date:

September 2012

Completion Date:

Related Keywords:

  • Anaplastic Large Cell Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Anaplastic
  • Lymphoma, Mantle-Cell

Name

Location

Arizona Cancer Center - TucsonTucson, Arizona  85724-5024