Belinostat and Yttrium Y 90 Ibritumomab Tiuxetan in Patients W/Relapsed Aggressive B-Cell NHL
Condition: Anaplastic Large Cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Mantle Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Anaplastic; Recurrence
Intervention: belinostat; rituximab; yttrium Y 90 ibritumomab tiuxetan
Intervention description: Given IV; Given IV; Given IV
Intervention MeSH terms: Rituximab; Belinostat; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study looks at what effects (good and bad) a drug called PXD-101 (belinostat) in
      combination with the radioactive drug Zevalin (yttrium Y 90 ibritumomab tiuxetan) has on
      patients with relapsed aggressive (high-risk) non-Hodgkin lymphoma. Studies in the laboratory
      suggest that drugs such as PXD101 can act upon specific cancer cell processes to cause either
      death of the cancer cells or prevention of their growth. In human studies with a small number
      of patients with this lymphoma, PXD-101 has shown the ability to shrink and slow tumor
      growth. When Zevalin is delivered directly to the tumor, the lymphoma cells are destroyed and
      this may result in the disappearance of the tumor (remission)
    

Eligibility criteria:

        Inclusion Criteria:

          -  Biopsy confirmed, CD20 positive diffuse large B-cell lymphoma, primary mediastinal
             b-cell lymphoma, mantel cell lymphoma, transformed indolent lymphoma, high
             grade-B-cell lymphoma; AND bone marrow must show =< 20% CD20+ B-cells with >= 15%
             cellularity within 42 days of study registration

          -  Any stage disease

          -  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

          -  Must have a diagnostic quality CT scan of the chest, abdomen and pelvis OR baseline
             PET-CT scan performed within 28 days prior to registration

          -  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

          -  To determine prior drug regimens: 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

          -  No clinical evidence of CNS involvement by lymphoma, any lab (eg., LDH or radiographic
             tests performed to access CNS involvement must be negative and must be performed
             within 42 days prior to registration

          -  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

          -  AST (SGOT)/ALT(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

          -  EKG with no significant abnormalities within 28 days prior to registration

          -  Women of child-bearing potential and men must agree to use adequate contraception

        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