NCT01493414: JUMP

INC424 for Patients With Primary Myelofibrosis, Post Polycythemia Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis.

Completed Phase 3 Results posted Last updated 26 April 2019

What this trial tests

Phase 3 trial testing INC424 in Myelofibrosis in 2,233 participants. Completed in 26 January 2017.

Timeline

16 August 2011

Primary endpoint
26 January 2017

26 January 2017

Quick facts

Lead sponsor	Novartis Pharmaceuticals
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	2,233
Start date	16 August 2011
Primary completion	26 January 2017
Estimated completion	26 January 2017
Sites	273 locations across Italy, Colombia, Ireland, Poland, Tunisia, Russia, Belgium, Mexico

Drugs / interventions tested

• INC424 — full drug profile →

Conditions studied

• Myelofibrosis — all drugs for Myelofibrosis →

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Myelofibrosis. 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.

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 5 Years Primary · Baseline up to approximately 5 years

An adverse event (AE) is any untoward medical occurrence in a clinical trial participant regardless of causal relationship to study drug and regardless whether study drug has been administered. A serious adverse event (SAE) is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above mentioned criteria. A non-seriou

Adverse Events

Group	Value	95% CI
INC424	2153

Serious adverse events

Group	Value	95% CI
INC424	830

Percentage of Participants With at Least 50% Reduction in Spleen Length Secondary · Baseline up to approximately 5 years

Spleen length was assessed by manual palpation. Assessment of spleen response was repeated until early discontinuation of the study drug and also at study completion (28 days post end of treatment visit).

Group	Value	95% CI
INC424	71.7	69.7 – 73.7

Number of Participants With Best Overall Response (BOR) up to 5 Years According to Spleen Length Secondary · Baseline up to approximately 5 years

Overall response is analyzed using the spleen response, as assessed by the investigator and also by deriving the response using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria. Participants with spleen length at baseline between 5 and 10 cm were reported as Responders if reporting non palpable spleen; Stable disease does not meet criteria for response or disease progression and Progressive disease with an increase of 100% from baseline in spleen length. Participants with spleen length at baseline more than 10 cm were reported as Responders w

Spleen length at baseline-Less than 5 cm

Group	Value	95% CI
INC424 - Responders	NA
INC424 - Stable Disease	NA
INC424 - Progressive Disease	NA
INC424 - Missing	NA

Spleen length at baseline-Between 5 and 10 cm

Group	Value	95% CI
INC424 - Responders	421
INC424 - Stable Disease	334
INC424 - Progressive Disease	1
INC424 - Missing	9

Spleen length at baseline-More than 10 cm

Group	Value	95% CI
INC424 - Responders	742
INC424 - Stable Disease	463
INC424 - Progressive Disease	0
INC424 - Missing	19

Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Secondary · Baseline up to approximately 5 years

ECOG Performance Score has 5 grades. 0 = Fully active, able to carry out all pre-disease activities; 1 = Restricted in strenuous activity but ambulatory and able to carry out work of light or sedentary nature; 2 = Ambulatory and capable of all self-care but unable to carry out work activities. Active about 50% of waking hours; 3 = Capable of limited self-care, confined to bed/chair more than 50% of waking hours; 4 = Completely disabled; cannot carry on self-care. Totally confined to bed/chair. 5 = Death.

Baseline - Grade 0

Group	Value	95% CI
INC424	598
INC424	377
INC424	62
INC424	12

Baseline - Grade 1

Group	Value	95% CI
INC424	89
INC424	629
INC424	187
INC424	26

Baseline - Grade 2

Group	Value	95% CI
INC424	3
INC424	43
INC424	111
INC424	20

Baseline - Grade 3

Group	Value	95% CI
INC424	0
INC424	0
INC424	0
INC424	1

Baseline - Grade 4

Group	Value	95% CI
INC424	0
INC424	0
INC424	0
INC424	0

Baseline - Missing

Group	Value	95% CI
INC424	1
INC424	8
INC424	4
INC424	1

Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48 Secondary · Baseline and Week 48

The FACT-Lym questionnaire consists of a total of 42 questions divided between five subscales (i.e., physical well-being, social/family well-being, emotional well-being, functional well-being and lymphoma subscale). Each subscale questionnaire rates each question on a 5-point scale from 0 = Not at all to 4 = Very much. These scores were summed to three total sum scores, namely FACT-Lym score, FACT-Lym Trial Outcome Index (TOI), FACT-General (FACT-G) and FACT-Lym total score. Total scores: FACT-Lym=0-60, FACT-TOI=0-116, FACT-G total=0-108, FACT-Lym Total= 0-168. Higher scores are reflective of

FACT-Lymphoma Baseline

Group	Value	95% CI
INC424	42.3	± 10.20

FACT-Lymphoma Week 48

Group	Value	95% CI
INC424	47.9	± 8.47

FACT-Lymphoma TOI Baseline

Group	Value	95% CI
INC424	77.9	± 18.99

FACT-Lymphoma TOI Week 48

Group	Value	95% CI
INC424	86.8	± 16.42

FACT-Lymphoma total score Baseline

Group	Value	95% CI
INC424	113.9	± 24.01

FACT-Lymphoma total score Week 48

Group	Value	95% CI
INC424	123.3	± 22.34

FACT-G Baseline

Group	Value	95% CI
INC424	71.6	± 15.98

FACT-G Week 48

Group	Value	95% CI
INC424	75.5	± 15.59

Time to First Improvement in FACT-Lym, FACIT-Fatigue Score and ECOG Performance Status Secondary · Baseline up to approximately 5 years

Improvement was defined by the upper limit of the minimally important difference (MID). Patients with the best possible score at Baseline were excluded from this analysis because their HRQoL cannot be further improved. Responders and non-responders for each endpoint were defined based on change from baseline scores using pre specified cut-off points. Patients with an improved score compared to Baseline, for which the magnitude of the change was at least the cutoff value, were classified as responders; otherwise, as non-responders. The responder cutoff: ECOG cutoff=1, range=0 to 5, FACT-Lym cut

FACT-Lym Total score median time to improvement

Group	Value	95% CI
INC424	10.9	5.1 – 11.6

FACIT - Fatigue score median time to improvement

Group	Value	95% CI
INC424	4.6	4.4 – 4.6

ECOG score median time to improvement

Group	Value	95% CI
INC424	63.1	61.1 – 65.0

Medical Resource Utilization up to 5 Years Secondary · Baseline up to approximately 5 years.

Percentage of patients requiring medical resources (blood transfusions, hospitalization, emergency room visits, general practitioners or specialists consultations, urgent care or splenic irradiation) up to 5 years.

Baseline- Dependency

Group	Value	95% CI
INC424	129
INC424	29

Baseline- Independency

Group	Value	95% CI
INC424	480
INC424	1595

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years .. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

INC424

Serious: 830/2233 (37%)

Deaths: 205/2233

Serious adverse events (565 terms)

Reaction	System	INC424
Pneumonia	Infections and infestations	—
Anaemia	Blood and lymphatic system disorders	—
Pyrexia	General disorders	—
Cardiac failure	Cardiac disorders	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—
Sepsis	Infections and infestations	—
Abdominal pain	Gastrointestinal disorders	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—
Thrombocytopenia	Blood and lymphatic system disorders	—
Urinary tract infection	Infections and infestations	—
Atrial fibrillation	Cardiac disorders	—
Gastrointestinal haemorrhage	Gastrointestinal disorders	—
Septic shock	Infections and infestations	—
General physical health deterioration	General disorders	—
Respiratory tract infection	Infections and infestations	—
Acute kidney injury	Renal and urinary disorders	—
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—
Diarrhoea	Gastrointestinal disorders	—
Cardiac arrest	Cardiac disorders	—
Vomiting	Gastrointestinal disorders	—
Ascites	Gastrointestinal disorders	—
Asthenia	General disorders	—
Acute leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—

Other adverse events (24 terms — click to expand)

Reaction	System	INC424
Anaemia	Blood and lymphatic system disorders	—
Thrombocytopenia	Blood and lymphatic system disorders	—
Asthenia	General disorders	—
Pyrexia	General disorders	—
Diarrhoea	Gastrointestinal disorders	—
Fatigue	General disorders	—
Platelet count decreased	Investigations	—
Headache	Nervous system disorders	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Oedema peripheral	General disorders	—
Arthralgia	Musculoskeletal and connective tissue disorders	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—
Abdominal pain	Gastrointestinal disorders	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—
Neutropenia	Blood and lymphatic system disorders	—
Weight increased	Investigations	—
Alanine aminotransferase increased	Investigations	—
Pruritus	Skin and subcutaneous tissue disorders	—
Nausea	Gastrointestinal disorders	—
Constipation	Gastrointestinal disorders	—
Nasopharyngitis	Infections and infestations	—
Back pain	Musculoskeletal and connective tissue disorders	—
Urinary tract infection	Infections and infestations	—
Herpes zoster	Infections and infestations	—

Most-reported serious reactions: Pneumonia, Anaemia, Pyrexia, Cardiac failure, Dyspnoea, Sepsis, Abdominal pain, Respiratory failure.

Data from ClinicalTrials.gov NCT01493414 adverse events section.

Sponsor's own description

The primary objective of this study was to collect additional safety of INC424 in patients with Primary Myelofibrosis, Post Polycythemia Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis, who either received prior treatment with commercially available agents or who have never received treatment.

Publications & conference data

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

1. Safety and efficacy of ruxolitinib in an open-label, multicenter, single-arm phase 3b expanded-access study in patients with myelofibrosis: a snapshot of 1144 patients in the JUMP trial.
   Al-Ali HK, Griesshammer M, le Coutre P, Waller CF, et al · · 2016 · cited 131× · PMID 27247324 · DOI 10.3324/haematol.2016.143677
2. Primary analysis of JUMP, a phase 3b, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis, including those with low platelet counts.
   Al-Ali HK, Griesshammer M, Foltz L, Palumbo GA, et al · · 2020 · cited 92× · PMID 32017044 · DOI 10.1111/bjh.16462
3. Baseline factors associated with response to ruxolitinib: an independent study on 408 patients with myelofibrosis.
   Palandri F, Palumbo GA, Bonifacio M, Tiribelli M, et al · · 2017 · cited 73× · PMID 29108288 · DOI 10.18632/oncotarget.18674
4. Safety and efficacy of fedratinib, a selective oral inhibitor of Janus kinase-2 (JAK2), in patients with myelofibrosis and low pretreatment platelet counts.
   Harrison CN, Schaap N, Vannucchi AM, Kiladjian JJ, et al · · 2022 · cited 30× · PMID 35476316 · DOI 10.1111/bjh.18207
5. Analysis of predictors of response to ruxolitinib in patients with myelofibrosis in the phase 3b expanded-access JUMP study.
   Gupta V, Griesshammer M, Martino B, Foltz L, et al · · 2021 · cited 29× · PMID 33210570 · DOI 10.1080/10428194.2020.1845334
6. Efficacy and tolerability of Janus kinase inhibitors in myelofibrosis: a systematic review and network meta-analysis.
   Sureau L, Orvain C, Ianotto JC, Ugo V, et al · · 2021 · cited 26× · PMID 34315858 · DOI 10.1038/s41408-021-00526-z
7. The role of allogeneic stem-cell transplant in myelofibrosis in the era of JAK inhibitors: a case-based review.
   Tiribelli M, Palandri F, Sant'Antonio E, Breccia M, et al · · 2020 · cited 18× · PMID 31534197 · DOI 10.1038/s41409-019-0683-1
8. Association of Myelofibrosis Phenotypes with Clinical Manifestations, Molecular Profiles, and Treatments.
   Chifotides HT, Verstovsek S, Bose P. · · 2023 · cited 17× · PMID 37444441 · DOI 10.3390/cancers15133331