E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Refractory and/or Relapsed Richters Transformation (RT) |
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E.1.1.1 | Medical condition in easily understood language |
Richters Transformation (RT) |
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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 | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10058728 |
E.1.2 | Term | Richter's syndrome |
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 |
The principal research question is to assess how well refractory and/or relapsed Richter's Transformation responds to treatment with Selinexor. |
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E.2.2 | Secondary objectives of the trial |
The secondary questions relate to the following:
• To determine the Disease Control Rate (DCR = CR + PR + SD), as well as duration of DCR • To determine Progression Free Survival (PFS) • To determine PFS on selinexor versus the patient’s PFS(s) on prior therapy(s) for RT • To determine Overall Survival (OS) • To further evaluate toxicity of selinexor in this patient population • To assess Quality of Life using FACT-Lym Questionnaire
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- male and female patients aged 18 years or older - willing to sign a written informed consent document - possess a histologically confirmed diagnosis of DLBCL - All patients deemed fit for standard chemo-immunotherapy must have received at least one, and no more than two, prior regimens for RT including cytotoxic chemotherapy and anti-CD20 monoclonal antibodies. Patients who are currently deemed unfit for standard cytotoxic chemotherapy must have received one prior therapy, including an anti-CD20 monoclonal antibody therapy. - One or more measurable (> 1.5 cm in longest dimension) disease sites - Objective documented evidence of disease progression at study entry - Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 - Baseline platelet count ≥ 30,000/mm3 and absolute neutrophil count ≥ 500/mm3 - Patients who are hepatitis B PCR negative who have a recent (< 6 month) history of IVIG therapy - Adequate hepatic function: bilirubin ≤ 2 times the upper limit of normal (ULN) and AST and ALT < 2.5 times ULN - Adequate renal function - For both male and female patients, effective methods of contraception must be used throughout the study |
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E.4 | Principal exclusion criteria |
- Patients who are pregnant or lactating - Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 2 weeks prior to Cycle 1 Day 1 - Less than 1 month since completion of autologous stem cell transplantation or less than 3 months since completion of allogeneic stem cell transplantation - Major surgery within four weeks of Cycle 1 Day 1 - Unstable cardiovascular function - Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose. - Presence of central nervous system (CNS) leukaemia or lymphoma. - Known active hepatitis B virus (HBV) or C virus (HCV) infection - Impairment of gastrointestinal (GI) function or GI disease that could interfere with the absorption of selinexor - Inability or unwillingness to take supportive medications including a centrally acting appetite stimulant - Serious psychiatric or medical conditions that could interfere with treatment. - Participation in an investigational anti-cancer study within 2 weeks prior to Cycle 1 Day 1. - Concurrent therapy with approved or investigational anticancer therapeutic
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is Overall Response Rate (ORR) (as defined by the IWG Criteria) achieved by RT patients treated with single-agent selinexor. Supportive data will be provided by the duration of ORR (DOR). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint is overall response rate (ORR) achieved on or after Day 1 of Cycle 3, or at any 2nd cycle thereafter, by RT patients who have been treated with at least one dose of single-agent selixenor. |
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E.5.2 | Secondary end point(s) |
The secondary endpoints include the determination of the following: - DCR, including supportive data provided by duration of DCR - Progression Free Survival (PFS) - PFS on selinexor versus the patients PFS(s) on prior therapy(s) for RT - Overall Survival (OS), including OS from diagnosis and from initiation of selinexor - Further evaluation of toxicity of selinexor in this patient population - Assessment of Quality of Life using the FACT-Lym Questionnaire |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary end points will be evaluated at end of study. |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 15 |
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 |
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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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Treatment with selinexor will continue until the patient is removed from the study; there is no known maximal duration of selinexor therapy. All patients will be followed until disease progression, another withdrawal criterion is met, or death (unless lost to follow up). |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 31 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 31 |