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

Non-Hodgkin's Lymphoma Clinical Trial

— PXD101-CLN-6  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00274651
• Other study ID #: PXD101-CLN-6
• Status: Terminated
• Phase: Phase 2
• First received: January 10, 2006
• Last updated: July 7, 2015
• Start date: January 2006
• Est. completion date: July 2009

Study information

• Verified date: July 2015
• Source: Onxeo
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Federal Institute for Drugs and Medical DevicesFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Israel: Ministry of HealthThailand: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 53
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• belinostat

Locations

Country	Name	City	State
France	Hopitaux du Haut Leveque	Pessac
France	Hospital Purpan	Toulouse
Germany	Universitatsklinikum Essen	Essen
Israel	Hadassah University Hospital Ein Kerem	Jerusalem
Israel	Rabin Medical Center	Petach Tikva
Thailand	Songklanagarind Hospital, Prince of Songkla University	Hat Yai
Thailand	King Chulalongkorn Memorial Hospital	Patumwan
United States	Boston University Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MD Anderson Cancer Center	Houston	Texas
United States	Kansas City Cancer Center	Lenexa	Kansas
United States	Yale University School of Medicine	New Haven	Connecticut
United States	NYU Medical Center	New York	New York
United States	Leland Stanford Junior University	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Onxeo

Countries where clinical trial is conducted

United States,  France,  Germany,  Israel,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No