A Phase II Clinical Trial of PXD101 in Patients With Recurrent or Refractory Cutaneous and Peripheral T-Cell Lymphomas (PXD101-CLN-6)

• ClinicalTrials.gov Identifier: NCT00274651
• Recruitment Status: Terminated
• First Posted: January 11, 2006
• Results First Posted: October 27, 2014
• Last Update Posted: July 28, 2015
• Sponsor: Onxeo
• Information provided by (Responsible Party): Onxeo

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Cutaneous T-Cell Lymphoma; Peripheral T-Cell Lymphoma; Non-Hodgkin's Lymphoma	Drug: belinostat	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 53 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Clinical Trial of PXD101 in Patients With Recurrent or Refractory Cutaneous and Peripheral T-Cell Lymphomas
• Study Start Date: January 2006
• Actual Primary Completion Date: July 2009
• Actual Study Completion Date: July 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm A; PXD101 1000 mg/m2 once daily for 5 days every 21 days	Drug: belinostat; Other Name: PXD101
Experimental: Arm B; PXD101 1000 mg/m2 once daily for 5 days every 21 days	Drug: belinostat; Other Name: PXD101

Outcome Measures

Primary Outcome Measures :

1. Objective Response Rate in Patients With Recurrent or Refractory Cutaneous T-cell Lymphoma (CTCL) [ Time Frame: throughout the study, or for a maximum of 2 years ]
   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.
2. Objective Response Rate in Patients With Recurrent or Refractory Peripheral T-cell Lymphoma (PTCL)) [ Time Frame: throughout the study, or for a maximum of 2 years ]
   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.

Secondary Outcome Measures :

1. Time to Progression [ Time Frame: throughout the study, or for a maximum of 2 years ]
   Time to progression was defined as the interval between the first date of treatment and the first notation of disease progression.
2. Time to Response [ Time Frame: throughout the study, or for a maximum of 2 years ]
   Time to response was defined as the interval between the first date of treatment and the first notation of response.
3. Duration of Response [ Time Frame: throughout the study, or for a maximum of 2 years ]
   Duration of response was defined as the time from first notation of response until the time of first notation of disease progression.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, California

Leland Stanford Junior University

Stanford, California, United States, 94305

United States, Connecticut

Yale University School of Medicine

New Haven, Connecticut, United States, 06520

United States, Kansas

Kansas City Cancer Center

Lenexa, Kansas, United States, 66214

United States, Massachusetts

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02115

Boston University Medical Center

Boston, Massachusetts, United States, 02118

United States, New York

NYU Medical Center

New York, New York, United States, 10016

United States, Ohio

Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

United States, Texas

MD Anderson Cancer Center

Houston, Texas, United States, 77030

France

Hopitaux du Haut Leveque

Pessac, France, 33604

Hospital Purpan

Toulouse, France, 31059

Germany

Universitatsklinikum Essen

Essen, Germany, 45147

Israel

Hadassah University Hospital Ein Kerem

Jerusalem, Israel, 91120

Rabin Medical Center

Petach Tikva, Israel, 49100

Thailand

Songklanagarind Hospital, Prince of Songkla University

Hat Yai, Thailand, 90110

King Chulalongkorn Memorial Hospital

Patumwan, Thailand, 10330

Sponsors and Collaborators

Onxeo

Investigators

• Study Director: e-mail contact via enquiries@topotarget.com; Onxeo

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Foss F, Advani R, Duvic M, Hymes KB, Intragumtornchai T, Lekhakula A, Shpilberg O, Lerner A, Belt RJ, Jacobsen ED, Laurent G, Ben-Yehuda D, Beylot-Barry M, Hillen U, Knoblauch P, Bhat G, Chawla S, Allen LF, Pohlman B. A Phase II trial of Belinostat (PXD101) in patients with relapsed or refractory peripheral or cutaneous T-cell lymphoma. Br J Haematol. 2015 Mar;168(6):811-9. doi: 10.1111/bjh.13222. Epub 2014 Nov 17.

• Responsible Party: Onxeo
• ClinicalTrials.gov Identifier: NCT00274651
• Other Study ID Numbers: PXD101-CLN-6
• First Posted: January 11, 2006
• Results First Posted: October 27, 2014
• Last Update Posted: July 28, 2015
• Last Verified: July 2015

Keywords provided by Onxeo:

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

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Belinostat; Antineoplastic Agents; Histone Deacetylase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action