Safety and efficacy study of INC424 in patients with myelofibrosis

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2010-024473-39-BE
• Date of registration: 16/06/2011
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• 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) of post polycythemia vera myelofibrosis (PPV MF) or post-essential thrombocythemia myelofibrosis (PET-MF)
• Date of first enrolment: 30/09/2011
• Target sample size: 2484
• 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: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no 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

Algeria, Argentina, Austria, Belgium, Brazil, Canada, Colombia, Czech Republic, Egypt, Germany, Greece, Hungary, Ireland, Israel, Italy, Kuwait, Mexico, Morocco, Poland, Portugal, Russian Federation, Saudi Arabia, Slovakia, South Africa, Spain, Thailand, Tunisia, United Arab Emirates, Venezuela, Bolivarian Republic of

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

Key inclusion & exclusion criteria

Inclusion criteria:
1. patient must give written informed consent according to local guideliens prior to any screening procedure
2. patients must not be eligible for another ongoing INC424 clinical trial
3. male or female patients aged > or = 18 years of age
4. Patients must be diagnosed with PMF, PPV-MF or PET-MF, according to the 2008 revised International Standard Criteria , irrespective of JAK2 mutation status.
5. 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 with an enlarged spleen at the screening visit (assessment to occur at the Screening Visit). The prognostic factors, defined by the International Working Group (Cervantes 2009) are described in Section 1.1 and Section 5.2 and should be evaluated at the Screening Visit.
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 percentage count of < 10%.
8. Patients with adequate liver function defined as total bilirubin or
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 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 any
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:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1350
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 250

Exclusion criteria:
1. Patients eligible for hematopoietic stem cell transplantation (suitable
candidate and a suitable donor is available).
2. Patients with a history of malignancy in the past 3 years, except for
treated early stage squamous or basal cell carcinoma in situ.
5. Patients receiving any medications listed in the "Prohibited
Medications" listing
6. Impairment of GI function or GI disease that may significantly alter the absorption of INC424
7. Patients with cardiac disease which in the Investigator's opinion may jeopardize the safety of the patient or the compliance with the protocol.
8. Patients with currently uncontrolled or unstable angina, rapid or
paroxysmal fibrillation or recent (approximately 6 months) myocardial infarction or acute coronary syndrome.
9. Patients with clinically significant bacterial, fungal, parasitic or viral infection that requires therapy. Patients with acute bacterial infections requiring antibiotic use should delay screening/enrollment until the
course of antibiotic therapy has been completed.
10. Patients with known active hepatitis A, B, C or who are HIV-positive.
11. Patients with inadequate bone marrow reserve at baseline visit as demonstrated by:
(a) ANC that is = 1000/µL.
(b) Platelet count that is <50,000/µL without the assistance of growth factors, thrombopoietic factors or platelet transfusions.
12. Patients with any history of platelet counts < 50,000/µL or ANC <500/µL except during treatment for a MPD or treatment with cytotoxic therapy for any other reason.
13. Patients with coagulation parameters (PT, PTT, INR) >1.5 x ULN.
14. Patients with known hypersensitivity to INC424 or other JAK1/JAK2 inhibitors, or to its excipients.
15. Patients receiving ongoing treatment with another investigational medication or having been treated with an investigational medication within 30 days of study drug treatment.
16. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until termination of gestation, confirmed by a positive ßHCG laboratory test (> 5 mIU/mL).
17. Women of child-bearing potential, defined as all women
physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they are using highly effective contraception methods (see Appendix II) defined as:
- Total abstinence and
- Female sterilization
- Combination of any two of the following (a+b or a+c or b+c):
(a) Use of oral, injected or implanted hormonal methods of
contraception
(b) Placement of an intrauterine device (IUD) or intrauterine system (IUS)
(c) Barrier methods of contraception: Condom or Occlusive cap
(diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/ vaginal suppository
18. Patients who are unable to comprehend or are unwilling to sign an ICF.
19. Patients with active alcohol or drug addiction that would interfere with their ability to comply with the study requirements.
20. Patients with any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol.



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

Health Condition(s) or Problem(s) studied

primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (PPV MF) or Post essential thrombocythemia myelofibrosis (PET-MF)

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

Intervention(s)

Trade Name: Jakavi
Product Name: ruxolitinib
Product Code: INC424
Pharmaceutical Form: Tablet
INN or Proposed INN: Ruxolitinib
CAS Number: 1092939-17-7
Current Sponsor code: INC424
Other descriptive name: Ruxolitinib phosphate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Trade Name: Jakavi
Product Name: ruxolitinib
Product Code: INC424
Pharmaceutical Form: Tablet
INN or Proposed INN: Ruxolitinib
CAS Number: 1092939-17-7
Current Sponsor code: INC424
Other descriptive name: Ruxolitinib phosphate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

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

Primary end point(s): Safety:
Safety and tolerability will be collected by monitoring the frequency,
duration and severity of all grade AEs by the National Cancer Institute 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).
ChangesLaboratory values from Baseline to End of Treatment (serum chemistry and hematology).
Changes in weight from Baseline to each assessment point and at end of treatment.
Cardiac function as assessed by electrocardiograms (ECGs).
Changes in vital signs.

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

Secondary Objective: To access the best overall response rate of INC424 in patients with PMF,
PPV MF, or PET-MF as evaluated by the Investigator.
To collect (QoL) information in patients with PMF, PPV MF, or PET-MF
treated with INC424.
To document MRU in patients with PMF, PPV MF, or PET-MF treated with
INC424

Secondary Outcome(s)

Secondary end point(s): Quality of Life
- Change in ECOG PS from Baseline to each visit where measured.
-Change in Functional Assessment of Cancer Therapy for patients with
Lymphoma (FACT-Lym) version 4 from Baseline to each visit where
measured
- Change in Functional Assessment of Chronic Illness Therapy (FACIT)
Fatigue from baseline to each visit where measured
Medical resource utilization (MRU)
Medical resource utilization (MRU) will be assessed as follows:
- Frequency and duration of hospitalization from Baseline up to week 48
of therapy
- Frequency of emergency room visits from Baseline up to week 48 of
therapy.
- Frequency of general practitioner, specialist, and urgent care visits
from Baseline up to week 48 of therapy.
- Number of transfusions and transfusion dependency status end of
study.
- Splenectomy and use of splenic irradiation.
- Changes in use of concomitant medications for MPN symptom
management
Efficacy
- Best overall response to treatment as assessed by spleen palpation
(calculated as the percentage change in spleen length compared with
Baseline)
- Change in spleen length from Baseline to end of each visit.
- Changes in WBC and platelet count from Baseline will be summarized at
end of each visit/month of therapy and at end of treatment.
- Shift in fibrosis in the bone marrow from Baseline to worst/best value on study (where bone marrow biopsies are performed – not mandatory).
- Progression free survival, acute myeloid leukemia free survival and overall survival.
- In patients without splenomegaly, patient reported outcomes that measure symptoms of
the disease.

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)

2010-024473-39-AT

CINC424A2401

Source(s) of Monetary Support

Novartis Pharma Services AG