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

• Conditions: T-cell Lymphoma; MedDRA version: 9.1Level: LLTClassification code 10042971Term: T-cell lymphoma

• Registration Number: EUCTR2007-001396-11-DE
• Lead Sponsor: TopoTarget A/S

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-05-21
• Last Update Posted: 24 June 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 68

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
;
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).
;
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).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified