Safety and efficacy study of INC424 in patients with myelofibrosis

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2010-024473-39-IT
• Date of registration: 06/12/2011
• Prospective Registration: No
• Primary sponsor: NOVARTIS FARMA
• Public title: Safety and efficacy study of INC424 in patients with myelofibrosis
• Scientific title: An open-label, multicenter, expanded access study of INC424 for patients with primary myelofibrosis (PMF) or post polycythemia myelofibrosis (PPV MF) or postessential thrombocythemia myelofibrosis (PET-MF)
• Date of first enrolment: 28/11/2011
• Target sample size: 950
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-024473-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Austria, Belgium, Brazil, Canada, Colombia, Czech Republic, Germany, Greece, Hungary, Ireland, Italy, Korea, Republic of, Lebanon, Mexico, Poland, Portugal, Russian Federation, Saudi Arabia, Singapore, Slovakia, South Africa, Spain, Switzerland, Taiwan, Venezuela, Bolivarian Republic of

Contacts

• Name: Drug Regulatory Affairs
• Affiliation: NOVARTIS FARMA

• Name: Drug Regulatory Affairs
• Affiliation: NOVARTIS FARMA

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients must give written informed consent according to local guidelines prior to any screening procedures; 2. Patients must not be eligible for another ongoing INC424 clinical trial; 3. Male or female patients aged = 18 years of age; 4. Patients must be diagnosed with PMF, PPV-MF or PET-MF, according to the 2008 World Health Organization criteria, irrespective of JAK2 mutation status; 5. PMF patients 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. The prognostic factors, defined by the International Working Group are described in Section 1.1; 6. Patients with Intermediate-1 and splenomegaly, must have a palpable spleen measuring 5 cm or greater from the costal margin to the point of greatest splenic protrusion; 7. Patients with a peripheral blood blast count of < 10%; 8. Patients with adequate liver function defined as direct bilirubin = 2.0 x ULN, and ALT = 2.5 x ULN; 9. Patients with adequate renal function defined as serum creatinine = 2 x ULN; 10. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2; 11. Women of childbearing potential must have had a negative serum pregnancy test within 14 days prior to the administration of study drug; 12. Patients must have recovered or stabilized sufficiently from adverse drug reactions associated with prior treatments before beginning treatment with INC424.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 380
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 570

Exclusion criteria:
1.Patients eligible for hematopoietic stem cell transplantation; 2. Patients with a history of malignancy in the past 3 years, except for treated early stage squamous or basal cell carcinoma in situ 3. patients undergoing treatment with hematopoietic growth factor receptor agonists, granulocyte colony stimulant factor at nay time within 2 weeks prior to screening or 4 weeks prior to baseline; 4. Patients currently participating in COMFORT-I and COMFORT -II trials; 5.Patients receiving any medications listed in the ''prohibited medications'' listing; 6. Impairment of GI function or GI disease that may alter the absorption of INC424; 7. Patients with cardiac disease which my jeopardize the safety of the patient; 8. Patients with currently uncontrolled or unstable angina, rapid or paroxysmal fibrillation or recent myocardial infarction or acute coronary syndrome; 9. Patients with clinically significant infections (for further details see protocol); 10. Patients with known active hepatitis a, B, C or who are HIV –positive; 11. Patients with coagulation parameters; 12.Pregnant or nursing women.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (PPV MF) or Post essential thrombocythemia myelofibrosis (PET-MF)
MedDRA version: 14.0 Level: PT Classification code 10028537 Term: Myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: ruxolitinib
Product Code: INC424
Pharmaceutical Form: Tablet
INN or Proposed INN: ruxolitinib
Current Sponsor code: INC424
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Primary end point(s): Safety: - Clinical and laboratory parameters will be collected to evaluate study drug safety and toxicity; - Safety and tolerability will be collected by monitoring the frequency, duration and severity of all grade adverse events (AEs) by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v. 3 0), performing physical exams (PE), and evaluating changes in vital signs (VS), ECOG performance status (PS), electrocardiograms (ECGs) and serum chemistry and hematology results; - Grade 3 and 4 AEs, Serious Adverse Events (SAEs); - Physicians will be required to report all SAEs and pregnancies to Novartis or designee. Data collection forms and safety reporting requirements will be provided to physicians for this purpose. Physicians will be made aware of emerging safety issues via the same procedures utilized by Novartis to notify investigators in other trials; -Frequency of dose interruptions and discontinuations due to AEs.

Main Objective: To collect additional safety of INC424 in patients with PMF, PPV MF, or PET MF, who have either received prior treatment with commercially available agents or never received treatment

Secondary Objective: -To document the best overall response rate to INC424 in patients with PMF, PPV MF , or PET MF as evaluated by the investigator; -To collect quality of life (QoL) endpoints; - To document medical resource utilization

Timepoint(s) of evaluation of this end point: Monthly for the first 3 months, then every 3 months and at study discontinuation

Secondary Outcome(s)

Secondary end point(s): Quality of Life: - Change in ECOG PS from Baseline to each visit where measured; - Change in FACT-Lym from baseline to each visit where measured; - Change in Functional Assessment of Chronic Illness Therapy (FACIT): Fatigue from baseline to each visit where measured

Timepoint(s) of evaluation of this end point: Monthly for the first 3 months, then every 3 months and at study discontinuation

Secondary ID(s)

CINC424A2401

2010-024473-39-AT

Source(s) of Monetary Support

Novartis Pharma Services AG