We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01493414
Recruitment Status : Completed
First Posted : December 16, 2011
Last Update Posted : December 21, 2017
Sponsor:
Information provided by (Responsible Party):

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

Condition or disease Intervention/treatment Phase
Myelofibrosis Drug: INC424 Phase 3

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2232 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Multicenter, Expanded Access Study of INC424 for Patients With Primary Myelofibrosis (PMF) or Post Polycythemia Myelofibrosis (PPV MF) or Post-essential Thrombocythemia Myelofibrosis (PET-MF).
Actual Study Start Date : August 16, 2011
Primary Completion Date : January 26, 2016
Study Completion Date : January 26, 2016


Arms and Interventions

Arm Intervention/treatment
Experimental: INC424
5 - 25 mg twice a day, per os
Drug: INC424
All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 25 mg twice a day. No INC424 dose will exceed 25 mg BID orally.
Other Name: Ruxolitinib


Outcome Measures

Primary Outcome Measures :
  1. Number of participants with treatment related adverse events up to 5 years [ Time Frame: Baseline up to approximately 5 years. ]
    The occurrence of adverse events may be volunteered by the patient or obtained by non-directive questioning at each visit during the study or through physical examination, laboratory test, or other assessments.


Secondary Outcome Measures :
  1. Best overall response up to 5 years. [ Time Frame: 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 IWG MRT criteria. Spleen response is also analyzed by proportion of patients achieving at least 50% reduction in spleen length at any time during the study.

  2. Change in ECOG Performance Status up to 5 years. [ Time Frame: Baseline up to approximately 5 years. ]
    ECOG performance score will be summarized from baseline versus worst-post baseline scores.

  3. Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) total scores up to Week 48. [ Time Frame: Baseline to 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) which in turn contribute to three total sum scores, namely FACT-Lym Trial Outcome Index (TOI), FACT-General (FACT-G) total score and FACT- Lym total score.

  4. Medical resource utilization up to 5 years. [ Time Frame: Baseline up to approximately 5 years. ]
    Percentage of patients requiring medical ressources (blood tranfusions, hospitalization, emergency room visits, general practitioners or specialists consultations, urgent care or splenic irradiation) by quarter and up to 5 years.


Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Main Inclusion Criteria:

  1. Patients must not be eligible for another ongoing INC424 clinical trial.
  2. Patients must be diagnosed with PMF, PPV MF or PET-MF, according to the 2008 revised International Standard Criteria, irrespective of JAK2 mutation status..
  3. Patients with PMF requiring therapy must be classified as high risk (3 prognostic factors) OR intermediate risk level 2 (2 prognostic factors, no more), OR intermediate risk level 1 (1 prognostic factor, no more) with an enlarged spleen (assessment to occur at the Screening Visit).

    The prognostic factors, defined by the International Working Group are:

    • Age > 65 years;
    • Presence of constitutional symptoms (weight loss, fever, night sweats);
    • Marked anemia (Hgb < 10g/dL)*;
    • Leukocytosis (history of WBC > 25 x109/L);
    • Circulating blasts > 1%. * A hemoglobin value < 10 g/dL must be demonstrated during the Screening Visit for patients who are not transfusion dependent. Patients receiving regular transfusions of packed red blood cells will be considered to have hemoglobin < 10 g/dL for the purpose of evaluation of risk factors.
  4. Patients with Intermediate-1 disease and splenomegaly must have a palpable spleen measuring 5 cm or greater from the costal margin to the point of greatest splenic protrusion.
  5. Patients must have a peripheral blood blast count of < 10%.
  6. Patients with an ECOG performance status of 0, 1, or 2.
  7. Fedratinib pretreated patients with documented complete physical examination including full neurologic examination and cardiology assessment, thiamine level testing, and MRI of the brain if indicated based on signs or symptoms. Patients pretreated with fedratinib should have completed or be receiving thiamine supplementation according to the investigator's instructions.

Main Exclusion Criteria:

  1. Patients eligible for hematopoietic stem cell transplantation (suitable candidate and a suitable donor is available).
  2. Patients with history of malignancy in past 3 years except for treated, early-stage squamous or basal cell carcinoma in situ.
  3. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral INC424 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).
  4. Patients with cardiac disease which in the Investigator's opinion may jeopardize the safety of the patient or the compliance with the protocol.
  5. Patients with currently uncontrolled or unstable angina, rapid or paroxysmal atrial fibrillation or recent (approximately 6 months) myocardial infarction or acute coronary syndrome.
  6. Patients with clinically significant bacterial, fungal, parasitic or viral infection which require therapy. Patients with acute bacterial infections requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed.
  7. Patients with known active hepatitis A, B, C or who are HIV-positive.
  8. Patients with inadequate bone marrow reserve at the Baseline visit as demonstrated by:

    • Absolute neutrophil count (ANC) ≤ 1000/µL.
    • Platelet count < 50,000/µL without the assistance of growth factors, thrombopoietic factors or platelet transfusions.
  9. Patients with any history of platelet counts < 50,000/µL or ANC < 500/µL except during treatment for a myeloproliferative disorder or treatment with cytotoxic therapy for any other reason.
  10. In the case of ruxolitinib pretreated patients, ruxolitinib primary resistant patients defined as:

    • No spleen reduction within the first 12 weeks after front line therapy with ruxolitinib.

    AND

    • No reduction in symptoms within the first 12 weeks after first-line treatment with ruxolitinib.

  11. In the case of ruxolitinib pretreated patients, patients discontinuing ruxolitinib due to a Grade 4 AE related or suspected to be related to ruxolitinib.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01493414


  Show 273 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01493414     History of Changes
Other Study ID Numbers: CINC424A2401
2010-024473-39 ( EudraCT Number )
First Posted: December 16, 2011    Key Record Dates
Last Update Posted: December 21, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Myelofibrosis
Primary myelofibrosis
PMF
Post polycythemia myelofibrosis
PPV MF
Post-essential thrombocythemia myelofibrosis
PET-MF
INC424
Ruxolitinib

Additional relevant MeSH terms:
Primary Myelofibrosis
Polycythemia
Thrombocytosis
Thrombocythemia, Essential
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders