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NCT02598297: ReTHINK

Phase III Study Investigating the Efficacy and Safety of Ruxolitinib in Early Myelofibrosis Patients With High Molecular Risk Mutations.

Terminated Phase 3 Results posted Last updated 16 August 2019
What this trial tests

Phase 3 trial testing Ruxolitinib in Myelofibrosis With High Molecular Risk Mutations in 49 participants. Terminated before completion.

Timeline
3 February 2016
Primary endpoint
23 October 2017
23 October 2017

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 3
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment49
Start date3 February 2016
Primary completion23 October 2017
Estimated completion23 October 2017
Sites110 locations across Hong Kong, Italy, Japan, Taiwan, Poland, Denmark, Russia, Belgium

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Myelofibrosis With High Molecular Risk Mutations. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage Change in Spleen Volume From Baseline Secondary · From baseline and assessed on 12 week intervals until end of treatment (EOT)

Change in spleen volume (by MRI/CT) from baseline

Week 12
GroupValue95% CI
Ruxolitinib (INC424)-10.8± 24.45
Ruxolitinib Placebo9.1± 12.34
Week 24
GroupValue95% CI
Ruxolitinib (INC424)-17.8± 18.83
Ruxolitinib Placebo17.6± 17.78
Week 36
GroupValue95% CI
Ruxolitinib (INC424)-18.4± 31.62
Ruxolitinib Placebo32.5± 18.81
Week 48
GroupValue95% CI
Ruxolitinib (INC424)-23.5± 10.57
End of Treatment (EOT)
GroupValue95% CI
Ruxolitinib (INC424)-11.6± 8.08
Ruxolitinib Placebo18.1± 18.58
Percentage Change in Symptoms From Baseline Using MF-7 Secondary · From Baseline and assessed every 4 weeks until end of treatment

Percentage change from Baseline in MF-7 total symptom score and 7 individual symptoms at each visit was summarized with descriptive statistics. For this scale, symptoms range from 0 to 10 for the severity experienced within the past 24 hours, with 0 being for absence of symptoms and 10 for worst imaginable symptoms.

Total Score derived (TSD): Baseline (BL)
GroupValue95% CI
Ruxolitinib (INC424)6.6± 5.17
Ruxolitinib Placebo5.9± 5.56
TSD change from baseline @ W12
GroupValue95% CI
Ruxolitinib (INC424)-0.3± 4.45
Ruxolitinib Placebo0.5± 6.08
TSD change from baseline @ W24
GroupValue95% CI
Ruxolitinib (INC424)0.5± 3.71
Ruxolitinib Placebo-0.8± 6.44
TSD change from baseline @ W48
GroupValue95% CI
Ruxolitinib (INC424)-0.3± 3.06
TSD change from BL @ EOT
GroupValue95% CI
Ruxolitinib (INC424)1.1± 4.40
Ruxolitinib Placebo3.3± 9.53
Tiredness: Baseline (BL)
GroupValue95% CI
Ruxolitinib (INC424)1.8± 1.45
Ruxolitinib Placebo1.5± 1.53
Tiredness: change from baseline @ W12
GroupValue95% CI
Ruxolitinib (INC424)0.1± 1.47
Ruxolitinib Placebo0.4± 1.27
Tiredness: change from baseline @ W24
GroupValue95% CI
Ruxolitinib (INC424)-0.1± 0.76
Ruxolitinib Placebo1.1± 2.52
Number of Participants With Specific Subscale Scores (From Baseline) Using EQ-5D Secondary · From Baseline and assessed every 4 weeks until end of treatment

EQ-ED5 profiles were summarized at baseline and at each scheduled assessment for each of the 5 dimensions separately (Mobility, self-care, usual activities, pain discomfort, anxiety/depression) Only participants with baseline score and at least one non-missing post-baseline score during the treatment period were included. Percentages were based on all these evaluable participants. The 5 scores for mobility, self-care, usual activities, pain/discomfort and anxiety/depression are all self-explanatory (eg "I have no problems walking" to "I am unable to walk"), except for the following overall he

Mobility- Baseline: No problem
GroupValue95% CI
Ruxolitinib (INC424)17
Ruxolitinib Placebo18
Mobility- Baseline: Slight problems
GroupValue95% CI
Ruxolitinib (INC424)4
Ruxolitinib Placebo5
Mobility- Baseline: Moderate problems
GroupValue95% CI
Ruxolitinib (INC424)1
Ruxolitinib Placebo1
Mobility- Baseline: Extreme problems
GroupValue95% CI
Ruxolitinib (INC424)1
Ruxolitinib Placebo0
Mobility - Week 4:No prob.
GroupValue95% CI
Ruxolitinib (INC424)17
Ruxolitinib Placebo14
Mobility - Week 4: Slight problems
GroupValue95% CI
Ruxolitinib (INC424)4
Ruxolitinib Placebo7
Mobility - Week 4: Moderate problems
GroupValue95% CI
Ruxolitinib (INC424)1
Ruxolitinib Placebo2
Mobility - Week 8: No problem
GroupValue95% CI
Ruxolitinib (INC424)17
Ruxolitinib Placebo15

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to approx. 55.1 weeks.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Ruxolitinib (INC424)
Serious: 2/24 (8%)
Deaths: 0/24
Ruxolitinib Placebo
Serious: 1/24 (4%)
Deaths: 0/24

Serious adverse events (3 terms)

ReactionSystemRuxolitinib (INC424)Ruxolitinib Placebo
Tendon ruptureInjury, poisoning and procedural complications
Gastric cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
PneumonitisRespiratory, thoracic and mediastinal disorders
Other adverse events (12 terms — click to expand)

ReactionSystemRuxolitinib (INC424)Ruxolitinib Placebo
AnaemiaBlood and lymphatic system disorders
FatigueGeneral disorders
NasopharyngitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
CoughRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
HypertensionVascular disorders
ThrombocytopeniaBlood and lymphatic system disorders
PyrexiaGeneral disorders
Respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
Night sweatsSkin and subcutaneous tissue disorders

Most-reported serious reactions: Tendon rupture, Gastric cancer, Pneumonitis.

Data from ClinicalTrials.gov NCT02598297 adverse events section.

Sponsor's own description

Myelofibrosis patients with high molecular risk mutations have an intrinsically aggressive disease with increased risk of leukemic transformation and reduced overall survival. As there are no therapies currently established in the subset of high molecular risk patients with early myelofibrosis, the study aimed to evaluate ruxolitinib in this patient population.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

  1. JAK2 inhibitors for myeloproliferative neoplasms: what is next?
    Bose P, Verstovsek S. · · 2017 · cited 78× · PMID 28500170 · DOI 10.1182/blood-2017-04-742288
  2. Current treatment algorithm for the management of patients with myelofibrosis, JAK inhibitors, and beyond.
    Harrison CN, McLornan DP. · · 2017 · cited 22× · PMID 29222297 · DOI 10.1182/asheducation-2017.1.489
  3. Novel approaches in myelofibrosis.
    Koschmieder S. · · 2024 · cited 7× · PMID 39670187 · DOI 10.1002/hem3.70056
  4. Myelofibrosis: an update on drug therapy in 2016.
    Bose P, Verstovsek S. · · 2016 · cited 7× · PMID 27774820 · DOI 10.1080/14656566.2016.1252333

Verify or expand the search:

Other trials of Ruxolitinib

Trials testing the same drug.

Other recruiting trials for Myelofibrosis With High Molecular Risk Mutations

Currently open trials in the same condition.

Other Novartis Pharmaceuticals trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02598297.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing