E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diffuse Large B-cell Lymphoma |
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E.1.1.1 | Medical condition in easily understood language |
A Type of Blood Cancer (Diffuse Large B-Cell Lymphoma (DLBCL)) |
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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 | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012820 |
E.1.2 | Term | Diffuse large B-cell lymphoma NOS |
E.1.2 | System Organ Class | 100000004864 |
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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 efficacy of fostamatinib (200 mg bid) in patients with relapsed or refractory DLBCL, by assessing overall response rate (ORR) |
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E.2.2 | Secondary objectives of the trial |
* To evaluate ORR and durable response rate (DRR) of patients with two distinct molecular subtypes of relpased or refractory DLBCL; B-cell receptor activation positive (BCA+) and B-cell receptor activation negative (BCA-). Several BCA signatures may be considered and selected signature(s) will be evaluated in a further study
* To further evaluate the efficacy of fostamatinib (200 mg bid) in patients with relapsed or refractory DLBCL, by assessing duration of response (DoR) & progression free survival
* To further evaluate the safety and tolerability of fostamatinib (200 mg bid) in the treatment of patients with relapsed or refractory DLBCL
* To characterise the pharmacokinetics (PK) of R940406 (R406), the active metabolite of fostamatinib
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
* Aged at least 18 years of age
* Patients with relapsed or refractory diffuse large B-cell lymphoma who have previously received R-CHOP (or equivalent) chemo-immunotherapy and high dose chemotherapy with stem cell rescue, or who are ineligible for high dose therapy with stem cell rescue
* Measurable disease as defined by Cheson et al 2007 criteria
* One fresh pre-treatment excisional or core needle biopsy from suitable and accessible site
* World Health Organization (WHO) performance status 0 to 1 |
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E.4 | Principal exclusion criteria |
* Treatment with nitrosurea, mitomycin C, investigational agents or study drugs w/in28 days of first dose of study treatment, any other chemotherapy, immunotherapy or anticancer agents w/in 3 weeks of first dose of study treament, previous fostamatinib
* With the exception of alopecia, any unresolved toxicities from prior therapy or surgery greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1
* Uncontrolled hypertension (defined as >140mmHg systolic and/or > 90 mmHG diastolic at baseline with or without antihypertensive therapy)
* Evidence of tuberculosis (TB)
* Inadequate bone marrow reserve |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
A response rate of CR, PR, SD or relapsed disease will be assigned at week 8, 20, and 44 and/or final study visit |
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E.5.2 | Secondary end point(s) |
1) Durable Response Rate
2) Progression Free Survival
3) Duration of Response
4) Safety
5) PK - to characterize the pharmacokinetics of R940406 (R406), the active metabolite of fostamatini |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Week 8, 20, and 44 and/or final study visit
2) Week 8, 20, and 44 and/or final study visit
3) Week 8, 20, and 44 and/or final study visit
4) Safety will be assessed in terms of adverse events, other significant adverse events, laboratory data/vital signs collected at all visits (Week 0, 1,2,3,4,8,12,16,20,44)
5) Before dosing, and at 1, 2, 4 and 8 hours after dosing on days 1, 8, and 29 and at each clinic visit every 8 to 16 weeks. Pts who have dose reduced will have one post dose PK sample drawn 1 to 4 hours after receiving their first treatment at lower dose leve
6) Pretreatment Blood Samples |
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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 | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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 | 2 |
E.8.5 | The trial involves multiple Member States | No |
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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The last visit of the last subject undergoing the study |
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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 | 2 |
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 | 2 |
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 |