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

This study has been terminated.
(Enrollment stopped prior to reaching expected number of patients, study had accumulated sufficient data to allow a registration study in PTCL (PXD101-CLN-19))
Sponsor:
Information provided by (Responsible Party):
TopoTarget A/S
ClinicalTrials.gov Identifier:
NCT00274651
First received: January 10, 2006
Last updated: October 21, 2014
Last verified: October 2014
  Purpose

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 Intervention Phase
Cutaneous T-Cell Lymphoma
Peripheral T-Cell Lymphoma
Non-Hodgkin's Lymphoma
Drug: belinostat
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by TopoTarget A/S:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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:
  • Time to Progression [ Time Frame: throughout the study, or for a maximum of 2 years ] [ Designated as safety issue: No ]
    Time to progression was defined as the interval between the first date of treatment and the first notation of disease progression.

  • Time to Response [ Time Frame: throughout the study, or for a maximum of 2 years ] [ Designated as safety issue: No ]
    Time to response was defined as the interval between the first date of treatment and the first notation of response.

  • Duration of Response [ Time Frame: throughout the study, or for a maximum of 2 years ] [ Designated as safety issue: No ]
    Duration of response was defined as the time from first notation of response until the time of first notation of disease progression.


Enrollment: 53
Study Start Date: January 2006
Study Completion Date: July 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00274651

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
Boston University Medical Center
Boston, Massachusetts, United States, 02118
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
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
TopoTarget A/S
Investigators
Study Director: e-mail contact via enquiries@topotarget.com TopoTarget A/S
  More Information

No publications provided

Responsible Party: TopoTarget A/S
ClinicalTrials.gov Identifier: NCT00274651     History of Changes
Other Study ID Numbers: PXD101-CLN-6
Study First Received: January 10, 2006
Results First Received: June 30, 2014
Last Updated: October 21, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Israel: Ministry of Health
Thailand: Food and Drug Administration

Keywords provided by TopoTarget A/S:
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, Cutaneous
Lymphoma, T-Cell, Peripheral
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Belinostat
Antineoplastic Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014