E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042971 |
E.1.2 | Term | T-cell lymphoma |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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). |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Exhibiting Objective Response or Stable Disease as confirmed by severity assessment tool. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |