IPSS and IPSS-R higher Risk ( INT-2 and High risk IPSS
Conditions
Interventions
Product Name: Azacitidina Orale
Product Code: [CC-486]
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: AZACITIDINA
CAS Number: 320-67-2
Current Sponsor code: IMP 1
Concentration unit: mg
Sponsors
Dipartimento di Medicina Sperimentale e Clinica- Università di Firenze
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must satisfy the following criteria to be enrolled in the study: 1. Male or female subjects = 65 years of age at the time of signing the ICD; 2. Diagnosed, histologically confirmed at inclusion, - Int-2 or High according to IPSS, or - Very High, High or Intermediate according to IPSS-R, or - Hypoplastic AML (20-30% BM blasts, previosuly considered MDS RAEB-T) - myelodysplastic CMML (included in IPSS scoring, WBC =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: - Absence of confirmed hematological response ( IWG HI/PR/CR) after at least 4 to 6 months of azacitidine sc and maintenance of response for 2 additional cycles. - Inability to provide a valid informed consent. - Eligibility for HSCT - Active infection - Serum creatinine > 2 x ULN at screening. - ECOG performance status > 2 - Left ventricular ejection fraction < 50% by echocardiography - A history of repeated hospitalization for severe infections Systemic diseases that would prevent study treatment (e.g. uncontrolled hypertension, cardiovascular, renal, hepatic, metabolic, etc.) - Clinical or laboratory evidence of chronic Hepatitis B or Hepatitis C (definition of chronic hepatitis follows EASL 2017 criteria). - History of HIV positive test result (ELISA or Western blot). - ALT or AST over 3 times superior to ULN at screening. - Total bilirubin over 1.5 times superior to ULN at screening (patients with Gilbert syndrome are allowed to enter the study) - Patients participating in another clinical trial other than an observational registry study. - Patients with a history of another malignancy within the past 3 years, with the exception of basal skin carcinoma or cervical carcinoma in situ or completely resected colonic polyps carcinoma in situ. - History of non-compliance to medical regimens, or patients who are considered potentially unreliable and/or not cooperative. - Presence of a surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of study drug. - History of drug or alcohol abuse within the 12 months prior to enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To explore the feasibility of replacing sc azacitidine by the oral formulation CC-486, in patients responding to sc azacitidine. In this context, “feasibility” encompasses 3 main areas of objective assessment: - Maintenance or improvement of response to therapy after switching from sc azacitidine to (oral) CC-486, - Safety and tolerability of CC-486, - Patient Reported Outcomes regarding satisfaction with the oral regimen;Secondary Objective: - Response duration (CR/PR/HI) on CC-486 - Progression to acute myeloid leukemia (AML), and time to AML progression; - Progression free survival - Overall survival - Exploratory Objectives: measure modifications of the pattern of DNA methylation levels ( by ERRBS technique) during cc 486 treatment as compared with those evaluated at the moment of cessation of azacitidine sc administration.;Primary end point(s): -To determine maintenance of CR/CRi, PR or SD with HI -To determine Safety/ tolerability (type, frequency, severity, and relationship of AEs to study treatments; physical examinations, vital signs; clinical laboratory evaluations, and concomitant medication/therapy); -To determine the effect of CC 486 on health-related quality-of-life (HRQoL) by Patient-reported outcomes utilizing the EQ-5D;Timepoint(s) of evaluation of this end point: 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Time to relapse from CR/CRi, PR, SD with HI; -Time to discontinuation from treatment; Exploratory endpoints -to determine the presence of differentially methylated regions (DMRs) at baseline, and verify DMRs and modulation of the pattern of methylation during treatment. Then, transcriptional profile and correlation between expression and methylation will be investigated.;Timepoint(s) of evaluation of this end point: 24 months; 24 months; 24 months | — |
Countries
Italy
Contacts
Public ContactValeria Santini
Dipartimento di Medicina Sperimentale e Clinica
Outcome results
None listed