Primary Myelofibrosis
Conditions
Keywords
Primary Myelofibrosis, Hematologic Diseases, Myeloproliferative Disorders, INC424, Ruxolitinib
Brief summary
The aim of the study is to assess the efficacy and safety of restarting ruxolitinib after treatment interruption due to loss of response and/or adverse events.
Interventions
DRUGRuxolitinib
Starting dose was based on reason for previous discontinuation of ruxolitinib (i.e. loss of response or AE) and baseline platelet count. For participants who previously discontinued ruxolitinib due to loss of response, the starting dose was determined based on baseline platelet counts as follows: participants with a baseline platelet count of ≥ 200 x 109/L began dosing at 20 mg po bid; participants with a baseline platelet count of 100 x 109/L to \<200 x 109/L began dosing at 15 mg po bid. Participants who previously discontinued ruxolitinib due to an AE initiated therapy at a total daily dose 5 mg lower than the total daily dose prior to discontinuation.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of PMF, PPV MF or PET-MF, irrespective of JAK2 mutational status according to the 2008 revised International Standard Criteria * Peripheral blast count \< 10% * Requires therapy for MF in the opinion of the investigator * Received prior monotherapy treatment with ruxolitinib for at least 12 consecutive weeks and experienced treatment interruption because of lossof 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 * ECOG performance status 0, 1, 2, or 3 * Adequate bone marrow function * Written informed consent
Exclusion criteria
* Patients not initially responding (primary resistance) to ruxolitinib therapy * Patients who underwent a splenectomy or spleen radiation * Patients currently scheduled for bone marrow transplant * Patients who have discontinued ruxolitinib \< 14 days prior to screening * Patients who are not able to receive a starting dose of ruxolitinib of at least 15 mg total daily dose * Leukemic transformation * Inadequate renal function * Presence of clinically meaningful active bacterial, fungal, parasitic or viral infection which requires therapy * Previous history of Progressive Multifocal Leuko-encephalopathy (PML) * Clinically significant cardiac disease or significant concurrent medical condition
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of Patients Achieving ≥20% Reduction From Baseline in Spleen Volume | Week 24 |
Secondary
| Measure | Time frame |
|---|---|
| Patient Global Impression of Change (PGIC) Score | Week 1, Week 24 |
| Proportion of Patients Achieving ≥25% and ≥50% Reduction, Respectively, From Baseline in Total Symptom Score (MPN-SAF TSS) | Week 24 |
| Proportion of Patients Achieving ≥35% Reduction From Baseline in Spleen Volume | Week 24 |
| Change From Baseline in MPN-SAF TSS Score | Baseline, Week 24 |
| Change From Baseline in Spleen Length and Spleen Volume | Baseline, Week 24 |
| Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and EuroQol (EQ)-5D-5L Scores | Baseline, Day 1, Week 8, Week 12, Week 16, Week 24 |
| Proportion of Patients Achieving ≥25% and ≥50% Reduction, Respectively From Baseline, in Spleen Length | Week 24 |
Countries
Germany, Italy, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ruxolitinib All participants received ruxolitinib. | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Study terminated by Sponsor | 2 |
Baseline characteristics
| Characteristic | Ruxolitinib |
|---|---|
| Age, Continuous | 68.00 Years STANDARD_DEVIATION 9.165 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 3 |
| serious Total, serious adverse events | 2 / 3 |
Outcome results
Primary
Proportion of Patients Achieving ≥20% Reduction From Baseline in Spleen Volume
Time frame: Week 24
Population: The study was terminated early due to low enrollment. Analysis was not done.
Secondary
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and EuroQol (EQ)-5D-5L Scores
Time frame: Baseline, Day 1, Week 8, Week 12, Week 16, Week 24
Population: The study was terminated early due to low enrollment. Analysis was not done.
Secondary
Change From Baseline in MPN-SAF TSS Score
Time frame: Baseline, Week 24
Population: The study was terminated early due to low enrollment. Analysis was not done.
Secondary
Change From Baseline in Spleen Length and Spleen Volume
Time frame: Baseline, Week 24
Population: The study was terminated early due to low enrollment. Analysis was not done.
Secondary
Patient Global Impression of Change (PGIC) Score
Time frame: Week 1, Week 24
Population: The study was terminated early due to low enrollment. Analysis was not done.
Secondary
Proportion of Patients Achieving ≥25% and ≥50% Reduction, Respectively From Baseline, in Spleen Length
Time frame: Week 24
Population: The study was terminated early due to low enrollment. Analysis was not done.
Secondary
Proportion of Patients Achieving ≥25% and ≥50% Reduction, Respectively, From Baseline in Total Symptom Score (MPN-SAF TSS)
Time frame: Week 24
Population: The study was terminated early due to low enrollment. Analysis was not done.
Secondary
Proportion of Patients Achieving ≥35% Reduction From Baseline in Spleen Volume
Time frame: Week 24
Population: The study was terminated early due to low enrollment. Analysis was not done.