E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (PPV MF)and post essential thrombocythemia vera (PETMF) |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 10028537 |
E.1.2 | Term | Myelofibrosis |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 effect of re-treatment with ruxolitinib on reduction in spleen
volume of at least 20% from baseline, by Week 24 |
|
E.2.2 | Secondary objectives of the trial |
1. To evaluate the effect of re-treatment with ruxolitinib on reduction in spleen
volume of at least 35% from baseline, by Week 24
2. To evaluate the effect of re-treatment with ruxolitinib on reduction in spleen
length of at least 25% and 50% respectively, from baseline, by Week 24
3. To evaluate the effect of re-treatment with ruxolitinib on reduction in spleen
volume and length over time
4. To evaluate the safety after re-treatment with ruxolitinib
5. To evaluate the effect of re-treatment with ruxolitinib on reduction in MPNSAF
TSS of at least 25% and 50% respectively, from baseline, by Week 24
6. To evaluate the effect of re-treatment with ruxolitinib on reduction in MPNSAF
TSS over time
7. To evaluate the effect of re-treatment with ruxolitinib on Patient Global
Impression of Change (PGIC)
8. To evaluate the effect of re-treatment with ruxolitinib on EORTC QLQ-C30 and EQ-5D-5L |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Confirmed diagnosis of PMF, PPV MF or PET-MF, irrespective of JAK2 mutational status according to the 2008 revised International Standard Criteria
2. Peripheral blast count < 10%
3. Requires therapy for MF in the opinion of the investigator
4. Received prior monotherapy treatment with ruxolitinib for at least 12 consecutive weeks and experienced treatment interruption because of loss of response or adverse event Patients adhering to the Screening phase assessments and undergoing a a ruxolitinib-free washout period of a minimum of 1 week and a maximum of 8 weeks
5. ECOG performance status 0, 1, 2, or 3
6. Adequate bone marrow function
7. Written informed consent
Additional inclusion criteria as described in the protocol may apply. |
|
E.4 | Principal exclusion criteria |
1. Patients not initially responding (primary resistance) to ruxolitinib therapy
2. Patients who underwent a splenectomy or spleen radiation
3. Patients currently scheduled for bone marrow transplant
4. Patients who have discontinued ruxolitinib < 14 days prior to screening
5. Patients who are not able to receive a starting dose of ruxolitinib of at least 15 mg total daily dose
6. Leukemic transformation
7. Inadequate renal function
8. Presence of clinically meaningful active bacterial, fungal, parasitic or viral infection which requires therapy
9. Previous history of Progressive Multifocal Leuko-encephalopathy (PML)
10. Clinically significant cardiac disease or significant concurrent medical
condition
Additional exclusion criteria as described in the protocol may apply. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients achieving ≥20% reduction from baseline in spleen volume by Week 24 after re-treatment with ruxolitinib |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. Proportion of patients achieving ≥35% reduction from baseline in spleen volume by Week 24 after re-treatment with ruxolitinib
2. Proportion of patients achieving ≥25% and ≥50% reduction respectively, from baseline, in spleen length by Week 24 after re-treatment with ruxolitinib
3. Change in spleen length as well as in spleen volume from baseline to each visit where measured after re-treatment with ruxolitinib
4. Safety will be assessed by monitoring the frequency, duration and severity of Adverse Events, and evaluating changes in vital signs, electrocardiograms (ECGs), serum chemistry, hematology and urinalysis results
5. Proportion of patients achieving ≥25% and ≥50% reduction respectively, from baseline in total symptom score (MPN-SAF TSS) by Week 24 after re-treatment with ruxolitinib
6. Change in MPN-SAF TSS from baseline to each visit where measured after re-treatment with ruxolitinib
7. PGIC at each visit where measured after retreatment with ruxolitinib
8. Change in EORTC QLQ-C30 and EQ-5D-5L scores from baseline to each visit where measured after re-treatment with ruxolitinib |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. By Week 24
2. By Week 24
3. Each visit
4. Each visit
5. By Week 24
6. Each visit
7. Each visit measured
8. Each visit measured
|
|
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 | Yes |
E.6.13.1 | Other scope of the trial description |
patient impression of change and effect on quality of life |
|
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
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 |
Austria |
Brazil |
Canada |
China |
France |
Germany |
Greece |
Italy |
Spain |
Thailand |
United Kingdom |
|
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
|
The end of the study (last patient last visit) will occur after all patients have had their End of Treatment visits (early discontinuation or Week 24 visit), plus the 30-day follow-up, per protocol. |
|
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 | 0 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |