E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Epstein-Barr Virus-Positive (EBV+) Relapsed/Refractory Lymphomas |
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E.1.1.1 | Medical condition in easily understood language |
Epstein-Barr Virus-Positive (EBV+) Relapsed/Refractory Lymphomas |
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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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10071441 |
E.1.2 | Term | Epstein-Barr virus associated lymphoma |
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 |
To evaluate the anti-tumor activity of the combination treatment of nanatinostat (Nstat) with valganciclovir (VGCV) based on objective tumor response rates |
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E.2.2 | Secondary objectives of the trial |
To determine the duration of tumor control To determine survival outcomes To describe the safety profile of the combination treatment of Nstat with VGCV To generate pharmacokinetic (PK) data
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult patients age ≥18 years or as permitted by applicable local regulations at the time of informed consent. Patients must be able to swallow whole tablets. a. For patients with PTLD: Age ≥12 years and weighing ≥40 kg 2. EBV+ relapsed/refractory lymphoma following 2 or more prior systemic therapies 3. Patients must have received at least one course of an anti-CD20 immunotherapy, and at least one course of anthracycline-based chemotherapy 4. Hodgkin lymphoma: Must have received at least one course of antracycline-based chemotherapy. Patients with classical Hodgkin lymphoma should have failed or be ineligible for an anti-PD-1 agent and CD30-directed therapy. 5. For patients with ENKTL: Relapsed/ refractory disease following 1 or more prior systemic therapies. Patients must have failed an a sparaginase-containing regimen. 6. For patients with PTCL (PTCL, NOS and AITL): relapsed or refractory disease following 1 or more prior systemic therapies with a curative intent. 7. For patients with PTLD: Patients with relapsed or refractory EBV+ PTLD who have received at least one prior therapy must have received at least one course of an antiCD20 immunotherapy such as rituximab. For solid-organ transplant (SOT) patients, prior therapy also includes chemotherapy, administered concurrently or sequentially, unless chemotherapy is inappropriate. 8. No available therapies in the opinion of the investigator. 9. Not eligible for high-dose chemotherapy with allogeneic/autologous stem cell transplantation or CAR-T Therapy. 10. Measurable disease per Lugano 2007. 11. ECOG performance status 0, 1, 2. 12. Adequate bone marrow function. |
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E.4 | Principal exclusion criteria |
1. Presence or history of central nervous system (CNS) involvement by lymphoma. 2. Systemic anticancer therapy or CAR within 21 days. 3. Antibody (anticancer) agents within 28 days. 4. Less than 60 days from prior autologous hematopoietic stem cell or solid organ transplant. 5. Less than 90 days from prior allogeneic transplant. 6. Daily corticosteroids (≥20 mg of prednisone or equivalent) within week prior to Cycle 1 Day 1. 7. Inability to take oral medication, malabsorption syndrome or any other gastrointestinal condition (nausea, diarrhea, vomiting) that may impact the absorption of nanatinostat and valganciclovir. 8. Active infection requiring systemic therapy (Excluding viral upper respiratory tract infections
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E.5 End points |
E.5.1 | Primary end point(s) |
• Objective response rate (ORR) as assessed by an Independent Review Committee (IRC) per the 2007 International Working Group (IWG) criteria.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary efficacy endpoint is ORR assessed by an IRC every 8 weeks until 24 weeks, and then every 12 weeks for the remainder of the study.
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E.5.2 | Secondary end point(s) |
• Duration of response (DOR) • Time to next anti-lymphoma treatment • Progression-free survival • Time to progression • Overall survival (OS) • Pharmacokinetic (PK) parameters (eg, time to maximum plasma concentration [tmax], maximum plasma concentration [Cmax], area under the plasma concentration-time curve [AUC]).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Overall survival,Time to next anti-lymphoma treatment, Duration of response, Progression free survival |
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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 | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | No |
E.8.2.4 | Number of treatment arms in the trial | 8 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 |
Malaysia |
Singapore |
Hong Kong |
Taiwan |
Australia |
Brazil |
Canada |
Israel |
Korea, Republic of |
United Kingdom |
United States |
France |
Germany |
Italy |
Spain |
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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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The end of the study occurs when all patients have either progressed, discontinued, died, become lost to follow-up, or have maintained a CR, PR, or SD for at least 3 years, or when the trial is terminated by the Sponsor.
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |