Proliferative Chronic Myelomonocytic Leukemia (CMML) MedDRA version: 16.1 Level: LLT Classification code 10054350 Term: Chronic myelomonocytic leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Jakavi
Product Name: RUXOLITINIB
Product Code: INCB018424
Pharmaceutical Form: Tablet
INN or Proposed INN: Ruxolitinib
CAS Number: 1092939-17-7
Current Sponsor code: INCB018424
Concentrati
Sponsors
Grupo Español de Sindromes Mielodisplásicos (GESMD)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? Proliferative CMML according to French-American-British (FAB) diagnostic criteria. ? Proliferative CMML patients with CMML-specific prognostic scoring system (CPSS) low risk or intermediate 1; or intermediate-2 or high who are not transplant candidates. ? Patients must have a palpable spleen measuring 5 cm or greater from the costal margin to the point of greatest splenic. If not, a 15 cm or greater measured by ultrasonography. ? To understand and voluntarily sign an informed consent form. ? Age ?18 years at the time of signing the informed consent form. ? Be able to adhere to the study visit schedule and other protocol requirements. ? All previous cancer therapy must have been discontinued at least 4 weeks prior to treatment in this study. Patients carrying a somatic mutation involving the platelet derived growth factor beta (PDGF?) can be included if standard treatment with imatinib failed. ? ECOG performance status of ?2 at study entry ? Laboratory tests results within these ranges: - Creatinine clearance >30 mL/min. - AST (SGOT) and ALT (SGTP) ?2.5 x ULN ? Disease free of prior malignancies for ?5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma ?in situ? of the cervix or breast. ? Female subjects of childbearing potential must: - Understand that study drug is expected to have a teratogenic risk - Agree to use two effective contraception methods ? Male subjects must: - Agree to use condoms - Agree not to donate semen ? All subjects must: - Agree to abstain from donating blood - Agree not to share study drug with another person 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 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: ? Patients with inadequate bone marrow reserve as demonstrated by: - Absolute neutrophil count (ANC) that is ? 1000/?L. - Platelet count that is <50,000/?L without the assistance of growth factors, thrombopoietic factors or platelet transfusions. ? Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent the subject from signing the informed consent form. ? Patient transplant candidates with CMML specific prognostic scoring system (CPSS) intermediate 2 or high risk. ? Pregnant or breast feeding females (lactating females must agree not to breast feed while taking INC424). ? Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. ? To use any other experimental drug or therapy within 28 days of baseline. ? Any prior use of INC424 ? Concurrent use of other anti-cancer agents or treatments. ? Known positive for HIV or infectious hepatitis, type A, B or C. ? Any of concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study. For example: - Uncontrolled diabetes - Active or uncontrolled infection - Uncontrolled hypothyroidism - Acute or chronic liver or renal disease ? Platelet count less than 50 x109/L.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate clinical response in CMML patients treated with ruxolitinib (INC424) by the achieving: a) ?50% reduction in spleen size by ultrasonography from baseline to week 48 b) Patients achieving ?50% reduction in symptomatology as measured by the modified MPN-SAF TSS and EORTC QLQ-C30 at week 48.;Secondary Objective: To evaluate clinical response in CMML patients treated with ruxolitinib (INC424) at week 24, by the achieving: a) Patients achieving ?50% reduction in spleen size by ultrasonography b) Patients achieving ?50% reduction in symptomatology at week 24. Patients achieving ?50% reduction in spleen size by palpation length at week 24 and 48. To assess the evolution of blast and promonocytes between baseline/week 48. the positive CD34 levels between baseline and week 48. To describe hematological response with INC424 by evaluating blood cell counts. To evaluate overall and PFS at 48 weeks To describe cytokine levels and mutational status of a selected gene panel between baseline and week 48 (an intermediate analysis in week 24 To analyze biological improvement with INC424 in terms of cytokines levels and mutations between baseline and week 48 To evaluate the safety of ruxolitinib (INC424) in patients with CMML;Primary end point(s): 1. Percentage of participants achieving ?50% reduction from baseline in spleen ultrasonography length at week 48. 2. Change from Baseline in Myelofibrosis Total Symptom Score at week 48 Symptoms of CMML will be assessed using a modified MPN-SAF TSS(28) and Global Health Status/Quality of Life Scale of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30);Timepoint(s) of evaluation of this end point: ? To evaluate clinical response in CMML patients treated with INC424 by the achieving ?50% reduction in spleen size by ultrasonography from baseline to week 48. The proportion of patients meeting the condition will be calculated (as well as the 95% CI). ? | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Percentage of participants achieving ?50% reduction from baseline in spleen ultrasonography length at week 24. 2. Change from Baseline in Myelofibrosis Total Symptom Score at week 24 Symptoms of CMML will be assessed using a modified MPN-SAF TSS(28) 3. Change from baseline to week 24 in Health-Related Quality of Life Health-related Quality of life will be assessed using the Global Health Status/Quality of Life Scale of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). 4. Percentage of participants achieving ?50% reduction from baseline in spleen palpable length at week 48. 5. Percentage of participants achieving ?50% reduction from baseline in spleen palpable length at week 24. 6. Change from baseline in blood counts (hemoglobin, neutrophils, leukocytes, platelets, blast and monocytes) over time. 7. Change from baseline to week 48 in CD34 in peripheral blood. 8. Change from baseline in body weight over time 9. Change from baseline to week 48 in ECOG Performance Status 10. Rate of Overall Survival (OS) and Progression Free Survival (PFS) 28 days after week 48 in proliferative CMML subjects treated with INC424. In patients still alive at end of study, survival evaluation will be performed at 6 and 12 months. 11. To describe cytokine and mutation panel: - To evaluate the leves of cytokines described in a proposed cytokine panel and its correlation with symptoms: IL-1?, IL-1?, IL-2, IL-4, IL-6, IL-8, IL-10, IFN-?, TGF-?, TNF-?, EGF, VEGF, MCP-1, IL-3, IL-7, IL-13, IL-12p70 and IL-23. (Some critical cytokines, from T lymphocytes, that contributes to T cell differentiation, effect or and inflammatory activity). Also we will analyze oncostatin, LAP, trombospondin and leptin as prognostic markers. - To evaluate the mutational status of the genes included in the panel detailed below: ASXL1, BCOR, BCORL1, CBL, CEBPA, DNMT3A, EED, ETV6, EZH2, FLT3, IDH1, IDH2, JAK2, KDM6A, K | — |
Countries
Spain
Contacts
Public ContactAngel Pérez
Dynamic Science
Outcome results
None listed