Myeloproliferative Diseases MedDRA version: 20.0 Level: LLT Classification code 10074691 Term: Post polycythaemia vera myelofibrosis System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Jakavi
Product Name: Jakavi
Pharmaceutical Form: Tablet
INN or Proposed INN: RUXOLITINIB
Other descriptive name: RUXOLITINIB
Concentration unit: mg milligram(s)
Concentration type: equal
C
Sponsors
Grupo Español de Enfermedades Mieloproliferativas GEMFIN
Eligibility
Sex/Gender
All
Inclusion criteria
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 25 x109/L). ? Circulating blasts = 1%. *A hemoglobin value 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
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 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. Valvul
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to determine the maximum tolerated dose (MTD) and the recommended phase III dose (RP3D) of ruxolitinib when administered in combination with nilotinib 300mg twice a day (BID) and prednisone 50mg every other day (EOD).;Secondary Objective: The secondary objectives of the study are the follows: ? To evaluate the safety profile of ruxolitinib, nilotinib and prednisone administered in combination. ? To evaluate the clinical activity of ruxolitinib, nilotinib and prednisone administered in combination.;Primary end point(s): The primary measure is the occurrence of DLTs. A DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 28 days (cycle 1 day 1 to cycle 1 day 28) of treatment with ruxolitinib, nilotinib and prednisone and meets any of the DLT criteria;Timepoint(s) of evaluation of this end point: AE that occurs within the first 28 days (cycle 1 day 1 to cycle 1 day 28) of treatment with ruxolitinib, nilotinib and prednisone . | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety data will be collected by monitoring the frequency, duration and severity of AEs graded by the Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute (version 4.0; Appendix 3), performing physical examinations, and evaluating changes in vital signs, Eastern Cooperative Oncology Group (ECOG) performance status, laboratory values and ECGs throughout the study. • All grade AEs, grade 3 and 4 AEs, and SAEs. • Physical examination. • Change in vital signs and ECOG performance status. • Laboratory values (serum chemistry and hematology). • Cardiac function as assessed by ECGs. 5.3.2.2 SECONDARY EFFICACY ENDPOINTS The secondary efficacy measures are as follows: • The percentage of patients with at least 50% reduction in palpable spleen length at 24 and 48 weeks. • The percentage of patients who have a = 50% reduction from baseline to 12, 24 and 48 weeks in the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) (;Timepoint(s) of evaluation of this end point: The percentage of patients with at least 50% reduction in palpable spleen length at 24 and 48 weeks. • The percentage of patients who have a = 50% reduction from baseline to 12, 24 and 48 weeks in the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) ( | — |
Countries
Spain
Contacts
Public ContactDepartamento de Ensayos Clínicos
Dynamic Solutions S.L
Outcome results
None listed