A Phase II Clinical Trial of PXD101 in Patients With Recurrent or Refractory Cutaneous and Peripheral T-Cell Lymphomas

Study Overview
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Brief Summary
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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.

Official Title
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A Phase II Clinical Trial of PXD101 in Patients With Recurrent or Refractory Cutaneous and Peripheral T-Cell Lymphomas

Conditions
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Cutaneous T-Cell Lymphoma, Peripheral T-Cell Lymphoma, Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: belinostat


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>PXD101 1000 mg/m2 once daily for 5 days every 21 days | Drug: belinostat<br> <br> * Other names: PXD101;|
| Experimental: Arm B<br>PXD101 1000 mg/m2 once daily for 5 days every 21 days | Drug: belinostat<br> <br> * Other names: PXD101;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate in Patients With Recurrent or Refractory Cutaneous T-cell Lymphoma (CTCL) | Tumor response was assessed using Cheson (Cheson 2007) and SWAT criteria. The SWAT score represents the product of the percentage total body surface area (TBSA) involvement of each lesion type (patch, plaque, and tumor or ulceration), multiplied by a weighting factor. | throughout the study, or for a maximum of 2 years | 
| Objective Response Rate in Patients With Recurrent or Refractory Peripheral T-cell Lymphoma (PTCL)) | Tumor response was assessed using the revised criteria of Cheson (Cheson 2007).Tumor assessments were done using conventional radiographic methods, e.g. CT or CT/PET. | throughout the study, or for a maximum of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression | Time to progression was defined as the interval between the first date of treatment and the first notation of disease progression. | throughout the study, or for a maximum of 2 years | 
| Time to Response | Time to response was defined as the interval between the first date of treatment and the first notation of response. | throughout the study, or for a maximum of 2 years | 
| Duration of Response | Duration of response was defined as the time from first notation of response until the time of first notation of disease progression. | throughout the study, or for a maximum of 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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