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

Novartis

Status and phase: Completed; Phase 3

Conditions: Myelofibrosis

Treatments: Drug: INC424

Study type: Interventional

Funder types: Industry

Identifiers

NCT01493414

CINC424A2401

2010-024473-39 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 2,233 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 white blood cell (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 Eastern Cooperative Oncology Group (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 Adverse event (AE) related or suspected to be related to ruxolitinib.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

2,233 participants in 1 patient group

INC424

Experimental group

Description:

5 - 25 mg twice a day (BID)

Treatment:

Drug: INC424