E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult patients with relapsed or refractory PTCL. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10034623 |
E.1.2 | Term | Peripheral T-cell lymphoma unspecified |
|
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 |
Determine the efficacy of pralatrexate with concurrent vitamin B12 and folic acid supplementation when administered to patients with relapsed or refractory peripheral T-cell lymphoma PTCL |
|
E.2.2 | Secondary objectives of the trial |
Determine the safety of pralatrexate with concurrent vitamin B12 and folic acid supplementation when administered to patients with relapsed or refractory PTCL Determine the pharmacokinetic PK profile of pralatrexate when administered with vitamin B12 and folic acid supplementation |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Patient has histologically/cytologically confirmed PTCL, using the Revised European American Lymphoma REAL World Health Organization WHO disease classification a. T/Natural Killer NK cell leukemia/lymphoma b. Adult T-cell lymphoma/leukemia human T-cell leukemia virus HTLV 1 c. Angioimmunoblastic T cell lymphoma d. Blastic NK lymphoma with skin, lymph node, or visceral involvement e. Anaplastic large cell lymphoma, primary systemic type f. PTCL unspecified g. T/NK-cell lymphoma nasal h. Enteropathy-type intestinal lymphoma i. Hepatosplenic T cell lymphoma j. Extranodal peripheral T/NK-cell lymphoma unspecified k. Subcutaneous panniculitis T-cell lymphoma l. Transformed mycosis fungoides 2. Patient has documented progression of disease after at least 1 prior treatment. Patients may not have received experimental therapy as their only prior therapy. Patient has at least 1 biopsy from initial diagnosis or in the relapsed setting to confirm the diagnosis of PTCL. Patient has recovered from the toxic effects of prior therapy. Patients treated with monoclonal antibody therapy may be enrolled regardless of the time frame of the therapy if they have progression of disease. 3. Eastern Cooperative Oncology Group ECOG Performance Status 61603; 2. 4. At least 18 years of age. 5. Adequate hematological, hepatic, and renal function as defined by absolute neutrophil count ANC 1000/mL, platelet count 50,000/mL, total bilirubin 1.5 mg/dL, aspartate aminotransferase AST and alanine aminotransferase ALT 2.5 upper limit of normal ULN AST/ALT 5 ULN if documented hepatic involvement with lymphoma , creatinine 1.5 mg/dL or a calculated creatinine clearance 50 mL/min. 6. Women of childbearing potential must agree to practice a medically acceptable contraceptive regimen from study treatment initiation until at least 30 days after the last administration of pralatrexate and must have a negative serum pregnancy test within 14 days prior to the first day of study treatment. Patients who are postmenopausal for at least 1 year 12 months since last menses or are surgically sterilized do not require this test. 7. Men who are not surgically sterile must agree to practice a medically acceptable contraceptive regimen from study treatment initiation until at least 90 days after the last administration of pralatrexate. 8. Patient has given written informed consent IC . |
|
E.4 | Principal exclusion criteria |
1. Patient has a. Precursor T/NK neoplasms, with the exception of blastic NK lymphoma b. T cell prolymphocytic leukemia T-PLL c. T cell large granular lymphocytic leukemia d. Mycosis fungoides, other than transformed mycosis fungoides e. Se zary syndrome f. Primary cutaneous CD30 disorders Anaplastic large cell lymphoma and lymphomatoid papulosis 2. Active concurrent malignancy except non melanoma skin cancer or carcinoma in situ of the cervix . If there is a history of prior malignancy, the patient must be disease free for 5 years. 3. Congestive heart failure Class III/IV according to the New York Heart Association s Heart Failure Guidelines. 4. Uncontrolled hypertension. 5. Human immunodeficiency virus HIV -positive diagnosis and is receiving combination anti-retroviral therapy. 6. Patient has, or history of, brain metastases or central nervous system CNS disease. 7. Patient has undergone an allogeneic stem cell transplant. 8. Patient has relapsed less than 75 days from time of an autologous stem cell transplant. 9. Active uncontrolled infection, underlying medical condition including unstable cardiac disease, or other serious illness that would impair the ability of the patient to receive protocol treatment. 10. Patient has had major surgery within 2 weeks of study entry. 11. Receipt of any conventional chemotherapy or radiation therapy RT within 4 weeks 6 weeks for nitrosoureas or mitomycin C prior to study treatment or planned use during the course of the study. 12. Receipt of corticosteroids within 7 days of study treatment, unless patient has been taking a continuous dose of no more than 10 mg/day of prednisone for at least 1 month. 13. Use of any investigational drugs, biologics, or devices within 4 weeks prior to study treatment or planned use during the course of the study. 14. Previous exposure to pralatrexate. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
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 | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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.8.5 | The trial involves multiple Member States | Yes |
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 |
|
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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
| |
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 | 0 |
E.8.9.1 | In the Member State concerned days | |