Safety and efficacy study of INC424 in patients with myelofibrosis

• Register: EUCTR
• Last refreshed on: 5 February 2018
• Main ID: EUCTR2010-024473-39-DE
• Date of registration: 30/06/2011
• 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: 11/08/2011
• Target sample size: 1600
• 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, Korea, Republic of, Kuwait, Lebanon, Mexico, Morocco, Poland, Portugal, Russian Federation, Saudi Arabia, Singapore, Slovakia, South Africa, Spain, Switzerland, Taiwan, Thailand, Tunisia, United Arab Emirates, Venezuela, Bolivarian Republic of

Contacts

• Name: Medizinischer Infoservice
• Affiliation: Novartis Pharma GmbH

• Name: Medizinischer Infoservice
• Affiliation: Novartis Pharma GmbH

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 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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 <75,000/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)

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-

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)

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

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 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).
Laboratory 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 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.
- WBC and platelet count changes 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, efficacy assessments will only be
provided by the 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)

CINC424A2401

2010-024473-39-AT

Source(s) of Monetary Support

Novartis Pharma Services AG