A Phase II Clinical Trial of PXD101 in Patients With Recurrent or Refractory Cutaneous and Peripheral T-Cell Lymphomas
Condition: Cutaneous T-Cell Lymphoma; Peripheral T-Cell Lymphoma; Non-Hodgkin's Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous
Intervention: belinostat
Intervention MeSH terms: Belinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 53.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CTCL; PTCL; lymphoma; Non-Hodgkin's Lymphoma; Cutaneous T-Cell Lymphomas (CTCL); Peripheral T-Cell Lymphomas (PTCL); Other Types of Non-Hodgkin's Lymphoma; belinostat

Summary:

      Open-label, non-randomized trial to assess the effectiveness of PXD101 in patients with
      recurrent or refractory cutaneous or peripheral and other types of T-cell lymphomas. PXD101
      is a new, potent histone deacetylase (HDAC) inhibitor. Patients are treated with
      belinostat(PXD101) 1000 mg/m2 on days 1-5 of a 21 day cycle.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female with age > or = 18 years.

          -  Histologically confirmed diagnosis of cutaneous T-cell lymphoma (CTCL) or peripheral
             T-cell lymphoma (PTCL) or other T-cell non-Hodgkin's lymphoma (NHL).

          -  Must have failed at least one line of prior systemic therapy. No limitation in number
             of prior therapies. CTCL patients who are refractory or intolerant to oral Targretin
             are also eligible.

          -  The presence of measurable disease (defined as > or = 1 cm with radiographic imaging)
             for PTCL or stage 1B or greater disease for CTCL and assessable by the
             severity-weighted assessment tool (SWAT).

          -  Adequate bone marrow and hepatic function including the following:

               -  Absolute neutrophil count > or = 1,000 cells/mm3, platelets > or = 40,000/mm3

               -  Total bilirubin < or = 1.5 x upper normal limit or < or = 3 x upper normal limit
                  if hepatic involvement

               -  AST (SGOT) (aspartate aminotransferase), ALT (SGPT) (alanine aminotransferase) <
                  or = 2.5 x upper normal limit (< or = 5 x upper normal limit if hepatic
                  involvement)

               -  Hemoglobin > or = 9.0 g/dL.

          -  Serum potassium within normal range.

          -  Karnofsky performance status > or = 70%.

          -  Estimated life expectancy > 3 months.

          -  Signed informed consent approved by the Institutional Review Board (IRB).

        Exclusion Criteria:

          -  Anti-cancer therapies within 4 weeks of first PXD101 administration should be excluded
             unless toxicity from prior anti-cancer therapy has resolved or returned to baseline
             and cancer disease status warrants.

          -  Any use of investigational drugs within 4 weeks prior to study registration.

          -  Major surgery within 4 weeks of study drug administration.

          -  Prior allogeneic bone marrow transplant.

          -  A diagnosis of adult T-cell lymphoma/leukemia (ATLL) or precursor T-lymphoblastic
             lymphoma.

          -  Co-existing active infection or any co-existing medical condition likely to interfere
             with trial procedures. However, patients with progressing CTCL whose open skin lesions
             are frequently infected may not be excluded from this trial at the discretion of
             Investigators.

          -  Clinically significant cardiovascular disease including unstable angina pectoris,
             uncontrolled hypertension, and congestive heart failure related to primary cardiac
             disease, a condition requiring anti-arrhythmic therapy, history of sustained
             ventricular tachycardia, history of ventricular fibrillation or Torsade de Pointes,
             bradycardia (HR<50bpm) with or without a pacemaker, bifascicular block with a right
             bundle branch block and a left anterior block, ischemic or severe valvular heart
             disease, a myocardial infarction within 6 months or a left ventricular ejection
             fraction < 40% (by echocardiogram [ECHO] or multigated acquisition scan [MUGA]) within
             3 months of study enrolment.

          -  A marked baseline prolongation of QT/QTc ((corrected) QT) interval, e.g., repeated
             demonstration of a QTc interval > 450 milliseconds (msec). Long QT Syndrome; the
             required use of concomitant medication on belinostat infusion days that may cause
             Torsade de Pointes.

          -  Renal insufficiency defined as a calculated creatinine clearance of < 45 mL/min/1.73
             m2.

          -  A history of allergic reactions attributed to compounds of similar chemical or
             biological composition to PXD101 and L-arginine.

          -  Clinically significant central nervous system disorders with altered mental status or
             psychiatric disorders precluding understanding of the informed consent process and/or
             completion of the necessary studies.

          -  Patients requiring treatment for other malignant diseases or less than 5 years
             post-treatment completion for an invasive malignant disease (excluding non-melanotic
             skin cancers or cervical cancer in-situ). Patients with any history of melanoma should
             be excluded.

          -  Pregnant or breast-feeding women, and women of childbearing age and potential, who are
             not willing to use effective contraception. Male patients and/or their fertile female
             partners who are not willing to use contraceptives during the trial.

          -  Known infection with HIV, human T-cell leukemia virus type-1 (HTLV-1), hepatitis B or
             hepatitis C.