E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Peripheral T-Cell Lymphoma |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10034623 |
E.1.2 | Term | Peripheral T-cell lymphoma unspecified |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
The primary objective of the study is to compare efficacy of romidepsin when administered with CHOP versus CHOP alone in subjects with previously untreated peripheral T-cell lymphoma (PTCL) |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to compare Ro-CHOP and CHOP alone in terms of:
• Overall survival
• Overall Response Rate (ORR [PR+CR+CRu]) (according to the Response criteria for malignant lymphoma 1999)
• Duration of response
• Time to progression
• Time to treatment failure
• Safety
• Quality of Life (QoL)
• Response rates by PTCL histological subtypes
• Response rate by standard prognostic parameters
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must satisfy all following criteria to be enrolled in the study:
1. Males and females of 18 years of age to 80 years of age.
2. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Patients with histologically proven peripheral T-cell lymphoma (PTCL), not previously treated; the following subtypes as defined by the WHO classification (2008;2011) may be included, whatever the Ann Arbor stage (l-lV):
a. Nodal types:
i. PTCL, not otherwise specified
ii. Angioimmunoblastic T-cell lymphoma
iii. Anaplastic large cell lymphoma, ALK-negative type
b. Extra-nodal types:
i. Enteropathy-associated T-cell lymphoma
ii. Hepato-splenic T-cell lymphoma
iii. Subcutaneous panniculitis-like T-cell lymphoma
iv. Primary cutaneous gamma-delta T-cell lymphoma
v. Primary cutaneous CD8+ aggresive epidermotropic lymphoma
vi. Primary cutaneous CD4+ small/medium T-cell lymphoma
c. Other non classifiable peripheral T-cell lymphoma
5. ECOG performance status 0, 1 or 2
6. Negative pregnancy test for females of childbearing potential (FCBP)
7. Female patients of child bearing potential must use an effective method of birth control (i.e. hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide or abstinence) during treatment period and 1 month thereafter; Males must use an effective method of birth control during treatment period and 3 months thereafter.
8. Life expectancy of ≥ 90 days (3 months).
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E.4 | Principal exclusion criteria |
The presence of any of the following will exclude a patient from enrollment:
1. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study.
2. Any condition that confounds the ability to interpret data from the study.
3. Other types of lymphomas, e.g. B-cell lymphoma.
4. The following types of T cell lymphomas:
a. Adult T-cell lymphoma/leukemia (HTLV-1 related T-cell lymphoma)
b. Extranodal T-cell/NK-cell lymphoma, nasal type
c. Anaplastic large cell lymphoma, ALK-positive type
d. Cutaneous T cell lymphoma (mycosis fungoides, Sézary syndrome)
e. Primary cutaneous CD30+ T-cell lymphoproliferative disorder
f. Primary cutaneous anaplastic T-cell lymphoma
5. Previous treatment for PTCL with immunotherapy or chemotherapy except for short-term corticosteroids (duration of <=8 days) before randomization.
6. Previous radiotherapy for PTCL except if localized to one lymph node area.
7. Patients planned for autologous or allogeneic transplant as consolidation in first line.
8. Central nervous system-meningeal involvement
9. Contraindication to any drug contained in the chemotherapy regimen.
10. Subjects with HIV positivity.
11. Subjects with active hepatitis B or C. Chronic carriers of hepatitis B
without HBV DNA positive blood are eligible after advice from
hepatologist and initiation of prophylactic treatment if needed. Subjects
with non-active hepatitis C (with normal transaminases) are eligible.
Patients with HBc Ab+/ HBs Ab+/ HBs Ag- and HBV DNA- should be
referred to an hepatologist and a prophylactic treatment should be
initiated if needed
12. Any of the following laboratory abnormalities, except if secondary to the lymphoma:
a. Absolute neutrophil count (ANC) < 1,500 cells/mm3 (1.5 x 109/L),
b. Platelet count < 100,000/mm3 (100 x 109/L), or < 75,000/mm3 if bone marrow is involved,
c. Serum SGOT/AST or SGPT/ALT ≥ 3.0 x upper limit of normal (ULN),
d. Serum total bilirubin > 2 x ULN, except in case of hemolytic anemia,
e. K+ and Mg2+ levels < LLN, except if corrected per protocol guidance before beginning the romidepsin infusion.
13. Serum creatinine > 2.0 x ULN
14. Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast or untreated prostatic cancer without any plan for a treatment) unless the patient has been free of the disease for ≥ 3 years
15. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form
16. Any known cardiac abnormalities such as:
a. Patients with congenital long QT syndrome,
b. Corrected QT interval > 480 msec (using the Fridericia formula),
c. Myocardial infarction within 6 months of cycle 1 day 1,
d. History of or concomitant significant cardiovascular disease,
e. Ejection fraction <45% by MUGA scan or by echocardiogram.
17. Concomitant use of drugs that may cause a significant prolongation of the QTc.
18. Patients who have received more than 200 mg/m2 doxorubicin.
19. Concomitant use of strong CYP3A4 inhibitors (see Appendix)
20. Concomitant use of therapeutic warfarin due to a potential drug interaction. Use of a low dose of warfarin or another anticoagulant to maintain patency of venous access port and cannulas is permitted.
21. Clinically significant active infection.
22. Use of any standard or experimental anti-cancer drug therapy within 28 days of the initiation (Day 1) of study drug.
23. Pregnant or lactating females or women of childbearing potential not willing to use an adequate method of birth control for the duration of the study.
24. Patients institutionalized by official means or court order. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) assessed according to progression
criteria for malignant lymphoma 1999 by a Response adjudication
committee. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Tumor assessment (clinical examination, laboratory tests, pelvis, abdominal, chest and cervical CT scan, bone marrow examination) will be performed at baseline, at mid-treatment after 3 cycles (CT scan only) and 4 weeks after the last treatment dose. To ensure comparability, baseline and on-study methods for response assessment will be performed using identical techniques.
Follow-up assessment, including CT Scan, will be clinical visit every 3 months the first year, then every 4 months the 2nd year, and every 6 months thereafter.
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E.5.2 | Secondary end point(s) |
• Overall survival
• Overall Response Rate (ORR [PR+CR+CRu]) (according to the Response criteria for malignant lymphoma 1999)
• Duration of response
• Time to progression
• Time to treatment failure
• Safety
• Quality of Life (QoL)
• Response rates by PTCL histological subtypes
• Response rate by standard prognostic parameters
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Overall survival: 2 years after the end of treatment
• Overall Response Rate (ORR [PR+CR+CRu]): at the end of treatment
• Duration of response: all duration of the study
• Time to progression: all duration of the study
• Time to treatment failure: all duration of the study
• Safety: all duration of the study
• Quality of Life (QoL) :At randomization, at D1 of cycle 4, at evaluation at the end of treatment, and during follow-up every 3 months the first year, every 4 months the second year and every year during follow-up period until primary analysis
• Response rates by PTCL histological subtypes:at the end of treatment
• Response rate by standard prognostic parameters: at the end of treatment
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
association of romidepsin and CHOP versus CHOP alone |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
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 | No |
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 |
Australia |
Belgium |
France |
Germany |
Italy |
Korea, Democratic People's Republic of |
Spain |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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The end of the trial will be the end of follow up so approximately 5 years after the last patient randomized. |
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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 | 8 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 8 |