Clinical trial NCT00274651: A Phase II Clinical Trial of PXD101 in Patients With Recurrent or Refractory Cutaneous and Peripheral T-Cell Lymphomas
Official title: A Phase II Clinical Trial of PXD101 in Patients With Recurrent or Refractory Cutaneous and Peripheral T-Cell Lymphomas
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cutaneous T-Cell Lymphoma
Peripheral T-Cell Lymphoma
Non-Hodgkin's Lymphoma
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
Lead sponsor: Valerio Therapeutics
Sponsor class: INDUSTRY
First posted: 2006-01-11
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Objective Response Rate in Patients With Recurrent or Refractory Cutaneous T-cell Lymphoma (CTCL)
timeFrame: throughout the study, or for a maximum of 2 years
measure: Objective Response Rate in Patients With Recurrent or Refractory Peripheral T-cell Lymphoma (PTCL))
timeFrame: throughout the study, or for a maximum of 2 years
Secondary outcomes:
measure: Time to Progression
timeFrame: throughout the study, or for a maximum of 2 years
measure: Time to Response
timeFrame: throughout the study, or for a maximum of 2 years
measure: Duration of Response
timeFrame: throughout the study, or for a maximum of 2 years
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Leland Stanford Junior University
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Lenexa
country: United States
facility: Kansas City Cancer Center
state: Kansas
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Boston University Medical Center
state: Massachusetts
city: New York
country: United States
facility: NYU Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Pessac
country: France
facility: Hopitaux du Haut Leveque
city: Toulouse
country: France
facility: Hospital Purpan
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Jerusalem
country: Israel
facility: Hadassah University Hospital Ein Kerem
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Hat Yai
country: Thailand
facility: Songklanagarind Hospital, Prince of Songkla University
city: Patumwan
country: Thailand
facility: King Chulalongkorn Memorial Hospital
Study officials:
affiliation: Valerio Therapeutics
name: e-mail contact via enquiries@topotarget.com
role: STUDY_DIRECTOR
References:
citation: 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.