E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Aggressive EBV positive extranodal NK/T-cell lymphoma (ENKTCL) |
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E.1.1.1 | Medical condition in easily understood language |
Aggressive EBV positive extranodal NK/T-cell lymphoma (ENKTCL) is a rare type of cancer that affects some types of blood cells. It is associated with Epstein Barr Virus (EBV). |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the overall response rate per independent endpoint assessment |
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E.2.2 | Secondary objectives of the trial |
To assess the complete response rate (CR) To assess response duration To assess time to response To assess progression free survival (PFS) To assess disease free survival (DFS) To assess the overall survival (OS) To assess safety through the incidence of adverse events (AE) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
FOR SCREENING PHASE: 1. Diagnosis of extranodal NK/T lymphoma, per WHO classification, 4th ed., which must include EBV tumor positivity, measured either by EBV encoded RNA (EBER) or LMP1 immunostaining. 2. a) Clinically suspected or documented relapse/progression, at any time following at least one cycle of an asparaginase-based chemotherapy OR b) High-risk disease (stage III/IV, KPI groups 3-4 or IPI intermediate-high) at any time (regardless of chemotherapy status and disease relapse/ progression)* 3. Male or female ≥ 18 years of age. 4. Weigh ≥ 35 kg. 5. ECOG performance score 0-2, inclusively. 6. Negative β-hCG test in women of childbearing potential. 7. Able to understand and comply with the requirements of the study and to provide written informed consent.
*Option B is intended to allow for advance manufacture of product in high risk patients to ensure immediate availability at time of relapse.
FOR TREATMENT PHASE: 1. All Screening Phase inclusion criteria. 2. Documented relapse or progression following at least one prior cycle of an asparaginase-containing chemotherapy regimen. 3. At least one prior cycle of gemcitabine-based salvage chemotherapy, or alternative salvage regimen if patient has previously been treated with gemcitabine or if there is medical rationale for administration of an alternative salvage regimen. 4. a) Presence of measurable disease as defined by at least one of the following: (i) Revised Response Criteria for Malignant Lymphoma (Cheson 2007) (ii) The modified Response Evaluation Criteria in Solid Tumors (RECIST v1.1) (iii) For patients with skin disease, biopsy confirmation of cutaneous NK/T lymphoma. (Patients meeting any one of the above criteria will be assigned to Group A), OR b) No measurable disease (assigned to Arm B). 5. Completed most recent course of chemotherapy at least 2 weeks prior to first study drug dose. 6. Recovery from acute hematological, hepatic and renal chemotherapy-related toxicities as defined by ≤ Grade 1 according to NCI CTCAE v4.0. (Transfusion to achieve the hematological criteria is acceptable). 7. Life expectancy ≥ 8 weeks. 8. Pulse oximetry of ≥ 90% on room air. |
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E.4 | Principal exclusion criteria |
FOR SCREENING PHASE: 1. CNS lymphoma. 2. NK/T cell leukemia. 3. Known hypersensitivity to the investigational product or any components in the final formulation (e.g. DMSO and/ or HSA). 4. Positive laboratory test for anti-HIV 1,2; HBsAg, anti-HTLV-I; anti-HCV, or syphilis (Patients with anti-hepatitis B core antibody are eligible if negative for HBsAg). 5. Use of systemic corticosteroids >0.5 mg/kg/day prednisolone or equivalent dose of alternative corticosteroid within 10 days prior to obtaining 100 mL starting material. 6. Patient is pregnant or lactating. 7. Female patients of childbearing potential and male patients with partners of childbearing potential unwilling to use a highly effective method of birth control during the study and for 6 months after the study treatment is concluded. 8. Clinically significant medical condition e.g. pulmonary, neurological, cardiovascular, metabolic, or hematologic (including hemophagocytic lymphohistiocytosis) that could jeopardize patient safety, interfere with the objectives of the protocol, or limit patient compliance with study requirements, as determined by the Investigator. 9. Active second malignancy. 10. Previous non-hematological malignancy, except for adequately treated basal-cell carcinoma of skin or cervical carcinoma in-situ without current evidence of disease, unless the tumor was treated with curative intent more than 5 years prior to study entry. 11. Any prior allogeneic hematopoietic stem cell or solid organ transplant.
FOR TREATMENT PHASE: 1. All Screening Phase exclusion criteria. 2. Use of any investigational agents within prior 4 weeks. 3. Radiotherapy within prior 3 weeks. 4. Major surgery within prior 2 weeks. 5. Signs/ symptoms of severe infection within prior 2 weeks. 6. Systemic corticosteroids within 24 hours prior to study drug administration. 7. Symptoms of cardiac failure with New York Heart Association classification of III or IV. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall response rate, defined as best observed response (CR or PR) (Group A only) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Tumour response will be measured at day 60, day 180, day 270 and day 365. |
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E.5.2 | Secondary end point(s) |
Complete response rate (CR) (Group A only) Response duration (Group A only) Time to response (Group A only) Progression free survival (PFS) (Group A only) Disease free survival (DFS) Overall Survival (OS) Adverse Events (AEs) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Duration of study (up to 2 years after last dose). |
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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) | 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 | 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) | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 |
France |
Germany |
Korea, Republic of |
United Kingdom |
United States |
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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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Last subject long-term survival appointment. The final study visit occurs at the 12 month timepoint. Study participants will be followed for a further 18 months through telephone and/ or medical records such that end of study will occur when the last follow-up appointment for the last subject has been completed. |
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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 |
E.8.9.2 | In all countries concerned by the trial months | 6 |