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

• Register: EUCTR
• Last refreshed on: 24 June 2013
• Main ID: EUCTR2007-001396-11-DE
• Date of registration: 21/05/2007
• Prospective Registration: Yes
• Primary sponsor: TopoTarget A/S
• Public title: A Phase II Clinical Trial of PXD101 in Patients with Recurrent or Refractory Cutaneous and Peripheral T-Cell Lymphomas
• Scientific title: A Phase II Clinical Trial of PXD101 in Patients with Recurrent or Refractory Cutaneous and Peripheral T-Cell Lymphomas
• Date of first enrolment: 29/08/2007
• Target sample size: 68
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-001396-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

France, Germany

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female with age = 18 years.
2. A histologically confirmed diagnosis of CTCL or PTCL or other T-cell NHL(WHO/Revised European-American Lymphoma classification). ALCL patients
presenting with CD30+, alk-, and no extracutaneous involvement (i.e. confirmed
absence of systemic disease) will be enrolled in the CTCL arm
3. Patients must have failed at least one line of prior systemic therapy, and there is no limitation in number of prior therapies. For CTCL, patients who are refractory or
intolerant to oral Targretin are also eligible.
4. The presence of measurable disease (defined as = 1 cm with radiographic imaging) for PTCL or stage 1B or greater disease for CTCL and assessable by the severityweighted assessment tool (SWAT).
5. Adequate bone marrow and hepatic function including the following:
a. Absolute neutrophil count = 1,000 cells/mm3, platelets
= 40,000/mm3
b. Total bilirubin =1.5 x upper normal limitor =3 x upper limit if documented hepatic involvement with lymphoma
c. AST (SGOT) and ALT (SGPT) =2.5 x upper normal limit (=5 x upper normal limit if documented hepatic involvement with lymphoma.
6. Serum potassium within normal range.
7. Karnofsky performance status > 70%.
8. Estimated life expectancy greater than 3 months.
9. Signed informed consent approved by the Institutional Review Board.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Patients who have received anticancer therapies within 4 weeks of first PXD101
administration should be excluded unless toxicity from prior anticancer therapy has
resolved or returned to baseline and cancer disease status warrants. The exception is patients who have received alemtuzumab; these patients are excluded if they have received alemtuzumab within one year of first PXD101 administration.
2. Any use of investigational drugs within 4 weeks prior to study registration.
3. Major surgery within 4 weeks of study drug administration.
4. Prior allogenic bone marrow transplant.
5. A diagnosis of Adult T-cell lymphoma/leukemia (ATLL) or Precursor Tlymphoblastic
lymphoma.
6. 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.
7. 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 (LVEF) < 40% (by Echocardiogram (ECHO) or Multiple Gated Acquisition
Scan (MUGA)) within 3 months of study enrollment.
8. A marked baseline prolongation of QT/QTc interval, e.g., repeated demonstration of a QTc interval >450 msec; Long QT Syndrome; the required use of concomitant
medication on PXD101 infusion days that may cause Torsade de Pointes. (See Appendix A for a list).
9. Patients with renal insufficiency defined as a calculated creatinine clearance of <45
mL/min/1.73 m2 based on Cockroft and Gault’s method (Cockroft 1976) or an
alternative calculation method used locally.
10. Patients with a history of allergic reactions attributed to compounds of similar
chemical or biological composition to PXD101 and L-arginine.
11. 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.
12. Other malignant diseases requiring treatment and patients who are less than 5 years post-treatment completion for an invasive malignant disease (except for nonmelanotic skin cancers or cervical cancer in-situ.) Patients with any history of
melanoma should be excluded.
13. Pregnant or breast-feeding women and women of childbearing age and potential,
who are not willing to use effective contraception. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year)when used consistenrly and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner.) Male patients and/or their fertile female partners who are not willing to use contraceptives during the trial.
14. Known active infection with HIV, HTLV-1, hepatitis B or hepatitis C.
15. For study centers in France, patients that are not affiliated with social security (France only).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

T-cell Lymphoma
MedDRA version: 9.1 Level: LLT Classification code 10042971 Term: T-cell lymphoma

Intervention(s)

Product Name: PXD101
Product Code: PXD101
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Belinostat
CAS Number: 414864-00-9
Current Sponsor code: PXD101
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Primary end point(s): Exhibiting Objective Response or Stable Disease as confirmed by severity assessment tool.

Main Objective: To determine the efficacy of PXD101 treatment as measured by objective response rate. Objective response (OR) is best overall response of CR or PR. CTCL response assessment is based on the severity-weighted assessment tool (SWAT) (Stevens 2002) with Cheson criteria applied in addition for determination of PD. PTCL response will be assessed using the criteria of Cheson et al. (Cheson 2007).

Secondary Objective: To determine the efficacy parameters duration of response, time to response, and time to progression, plus to examine safety following PXD101 therapy as a single agent.

Secondary ID(s)

PXD101-CLN-6

2007-001396-11-FR