E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Lymphoid or myeloid neoplasm with 8p11 rearrangement known to lead to FGFR1 activation |
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E.1.1.1 | Medical condition in easily understood language |
Lymphoid or myeloid neoplasm with 8p11 rearrangement |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 primary objective of this study is to evaluate the efficacy of pemigatinib in subjects with myeloid/lymphoid neoplasms with FGFR1 rearrangement. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate the safety and efficacy of pemigatinib in subjects with myeloid/lymphoid neoplasms with FGFR1 rearrangement. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Men and women, aged 18 or older. • Documented lymphoid or myeloid neoplasm with 8p11 rearrangement known to lead to FGFR1 activation, based on standard diagnostic cytogenetic evaluation performed locally, before signing informed consent for this study. • Eligible subjects must a. Have relapsed after stem cell transplantation or after other disease modifying therapy, OR b. Not be current candidates for stem cell transplantation or other disease-modifying therapies. Note: All relapsed/refractory subjects must have evidence of either cytogenetic or hematological disease and have no evidence of residual toxicity (eg, graft-versus-host disease requiring treatment). • Life expectancy ≥ 12 weeks. • ECOG performance status 0 to 2. |
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E.4 | Principal exclusion criteria |
• Prior receipt of a selective FGFR inhibitor. • History of calcium and phosphate hemostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues (exception: commonly observed calcifications in soft tissues, such as the skin, kidney, tendons, or vessels due to injury, disease, and aging, in the absence of systemic mineral imbalance). • Current evidence of clinically significant corneal disorder/keratopathy (including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and keratoconjunctivitis, etc) or retinal disorder (including but not limited to macular/retinal degeneration, diabetic retinopathy, retinal detachment, etc) as confirmed by ophthalmologic examination. • Use of any potent cytochrome P450 3A4 inhibitors or inducers within 14 days or 5 half-lives (whichever is shorter) before the first dose of study drug. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is the proportion of subjects who achieve CR as determined by investigator assessment according to the response criteria listed in Appendix E of the protocol |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Investigators will assess response to treatment by evaluation of local peripheral blood results, bone marrow pathology, cytogenetics, and imaging for EMD at the frequencies listed in section 7.6 of the protocol. |
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E.5.2 | Secondary end point(s) |
The secondary endpoints for this study are as follows: • The proportion of subjects who achieve response, defined as a best response of CR or PR, as determined by investigator assessment according to the response criteria listed in Appendix E of the protocol. • The proportion of subjects who achieve a complete cytogenetic response (CCyR) as assessed by local analysis and investigator evaluation. • The proportion of subjects who achieve a partial cytogenetic response (PCyR) as assessed by local analysis and investigator evaluation. • Duration of CR, defined as the time from first assessment of CR to the earlier of disease progression or death due to any cause. • Duration of response, defined as the time from first assessment of CR or PR to the earlier of disease progression or death due to any cause. • Progression-free survival. • Overall survival. • Safety and tolerability, as assessed by evaluating the frequency, duration, and severity of AEs; through review of findings of physical examinations, changes in vital signs, and electrocardiograms (ECGs); and through clinical laboratory blood and urine sample evaluations. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Investigators will assess response to treatment by evaluation of local peripheral blood results, bone marrow pathology, cytogenetics, and imaging for EMD at the frequencies listed in section 7.6 of the protocol. |
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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 | No |
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) | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 |
Switzerland |
Canada |
Japan |
United Kingdom |
United States |
Austria |
Belgium |
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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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 | 1 |
E.8.9.1 | In the Member State concerned days | 1 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 1 |