Clinical trial of ruxolitinib in combination with nilotinib and prednisona for myelofibrosis: RuNiC study

Phase 1

• Conditions: Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]; Myeloproliferative Diseases; MedDRA version: 20.0Level: LLTClassification code 10074691Term: Post polycythaemia vera myelofibrosisSystem Organ Class: 100000004864

• Registration Number: EUCTR2016-005214-21-ES
• Lead Sponsor: Grupo Español de Enfermedades Mieloproliferativas GEMFI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-05-29
• Last Update Posted: 20 July 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

Patients are included in the study if all of the following criteria are met:
1.Patients must be 18 years or older.
2.Patients must be diagnosed with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemia-myelofibrosis (PET-MF) irrespective of JAK2 mutation status, guided by the criteria outlined in the 2008 World Health Organization (WHO) criteria for PMF9 and the proposed criteria for PPV-MF and PET-MF outlined by the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT)10.
3.Patient must be classified as at least intermediate risk level 1 (1 or more prognostic factors) with at least one criteria other than age. The prognostic factors, defined by the International Working Group are11:
?Age > 65 years.
?Presence of constitutional symptoms (weight loss > 10% in the year preceding the screening visit, unexplained fever, or excessive night sweats persisting for more than 1 month).
?Marked anemia (hemoglobin < 10g/dL)*.
?Leukocytosis (history of white blood cell count > 25 x109/L).
?Circulating blasts = 1%.
*A hemoglobin value < 10 g/dL must be demonstrated during the screening 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.Patient must have palpable spleen of at least 5 cm from the costal margin to the point of greatest splenic protrusion at screening.
5.Patients must have active symptoms of MF as measured by the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS). Demonstrated as a minimum of 5 points in at least one item (scale 0-10), or two items of at least 3 points (scale 0-10).
6.Patients naïve to JAK inhibitors treatment are eligible for treatment arm A. Patients non-responding to or relapsed after JAK inhibitors treatment must meet one of the following criteria at screening to be eligible for treatment arm B (patients with prior ruxolitinib [INC424] treatment must meet one of the criteria below after at least 12 weeks on ruxolitinib treatment):
?Patients with no improvement in spleen length and may or may not have a corresponding symptomatic improvement.
?Patients with less than a 25% spleen length reduction by palpation and may or may not have a corresponding symptomatic improvement.
?Patients that have had a 25% to 49% reduction in spleen length by palpation and without symptomatic improvement.
?Patients who have lost benefit from prior treatment with a JAK inhibitor as per investigator (i.e. increased spleen length from nadir >40% as measured by palpation and/or return of symptoms as per investigator’s assessment).
7.Platelet counts = 50 x 109/L not reached with the aid of transfusions at screening or cycle 1 day 1.
8.Patients with absolute neutrophil count > 1 x 109/L at screening without the use of granulocyte colony-stimulating factors.
9.Fasting plasma glucose = 120 mg/dL or < 6.7 mmol/L at screening.
10.Serum creatinine = 2 x upper limit of normal (ULN) at screening.
11.Patients with peripheral blood blast count of <5% at screening.
12.Patients with an ECOG performance status of 0, 1, or 2 at screening.
13.Patients must have discontinued all drugs used to treat underlying MF disease no later than 7 days prior to screening evaluation visit.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (1

Exclusion Criteria

Pregnant or nursing (lactating) women, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
-Women of child-bearing potential.
-Male sterilization (at least 6 months prior to screening).
-For female subjects on the study the vasectomized male partner should be the sole partner for that subject.

.Previous treatment with JAK inhibitors (including ruxolitinib [INC424]) that resulted in clinically significant toxicities at the discretion of the investigator.
Patient with clinically significant bacterial, fungal, parasitic or viral infection which require therapy at screening. Patients with acute bacterial infections requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed.
Patients with known active hepatitis B or C or with known HIV positivity (testing is not mandatory).
Patients with impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of ruxolitinib, nilotinib and prednisone at screening (e.g. uncontrolled nausea, vomiting, diarrhea, mal-absorption syndrome, small bowel resection).
Patient with a concurrent malignancy or malignancy within 3 years of screening, with the exception of adequately treated basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
Patient who has not recovered to grade 1 or better from any AEs (except alopecia, fatigue, nausea, vomiting) related to previous antineoplastic therapy before screening procedures are initiated.
Patients receiving the following treatments/medications:
An enzyme-inducing anti-epileptic drug within 2 weeks prior to starting study treatment.
Medication that has a known risk to prolong the QT interval or induce Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to starting study treatment.
Treatment with a potent systemic inhibitor or a potent systemic inducer of CYP3A4 at the time of screening and cannot be discontinued or switched to alternative medication prior to starting study treatment.
Any regular use of drugs that interferes with coagulation or inhibits platelet function. NOTE: low doses of aspirin = 150 mg/day and low molecular weight heparin are allowed.
Patients who have had splenic irradiation within 12 months prior to screening.
Patient has undergone the following invasive procedures:
Major surgical procedure, open biopsy or significant traumatic injury < 14 days prior to starting study drug or has not recovered from side effects of such therapy.
Patient has a history of cardiac dysfunction including any of the following:
Myocardial infarction within the past 6 months documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular ejection fraction (LVEF) function.
Documented congestive heart failure (New York Heart Association functional classification III-IV).
Documented cardiomyopathy.
Patient has active cardiac disease including any of the following:
LVEF < 50% as determined by (MUGA) or (ECHO).
QTc > 480 msec on screening (ECG) (QTcF, using the Fridericia formula).
Angina pectoris that requires the use of anti-anginal medication.
Ventricular arrhythmias except for benign premature ventricular contractions.
Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication.
Conduction abnormality requiring a pacemaker.
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Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified