Myelodysplastic syndrome high and Int-2, acute myeloid leukemia = 30% marrow blasts and chronic monocytic leukemia (CMML) type 2 MedDRA version: 16.1 Level: HLT Classification code 10028536 Term: Myelodysplastic syndromes System Organ Class: 100000004851
Conditions
Interventions
Product Code: SGI-110
Pharmaceutical Form: Lyophilisate and solvent for suspension for injection
INN or Proposed INN: SGI 110
Current Sponsor code: SGI 110
Concentration unit: mg milligram(s)
Concentr
Sponsors
Groupe Francophone des Myélodysplasies (GFM)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Myelodysplastic syndrome including the following categories of the WHO classification: refractory anemia with excess blasts (RAEB), non-proliferative chronic myelomonocytic leukemia (CMML) (leukocytes 10% marrow blasts), AML with 20-30% marrow blasts (RAEB-T according to the FAB classification), at screening time. 2. Prior treatment with azacitidine or decitabine for at least 6 courses without response (CR, PR, marrow CR or stable disease with HI according to IWG 2006 criteria) or relapsing after a response. Non responders will be eligible only in the absence of overt progression, ie AML progression (if patients had no AML at onset of azacitidine/decitabine) or doubling of marrow blast percentage between onset of azacitidine/decitabine and screening 3. IPSS score >1 (IPSS: Int-2 or High). 4. Age = 18 years. 5. Normal liver function, defined by total bilirubin and transaminases less than 1.5 times the upper limit of normal. 6. Normal renal function, defined by creatinine less than 1.5 times the upper limit of normal, creatinine clearance = 50 mL/min (according to MDRD formula rather than Cockroft formula in patients older than 65 years) . 7. Patient is known not to be refractory to platelet transfusions. 8. Written informed consent. 9. Patient must understand and voluntarily sign consent form. 10. Patient must be able to adhere to the visit schedule as outlined in the study and follow protocol requirements. 11. ECOG performance status between 0-2 at the time of screening. 12. Women of childbearing potential must: Agree to use effective contraception without interruption throughout the study and for a further 2 months after the end of treatment. 13. Men must: Agree to not conceive during the treatment and to use effective contraception during the treatment period (including periods of dose reduction or temporary suspension) and for a further 2 month after the end of treatment if their partner is of childbearing potential. 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 54 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 54
Exclusion criteria
Exclusion criteria: 1. Severe infection or any other uncontrolled severe condition. 2. Significant cardiac disease - NYHA Class III or IV or having suffered a myocardial infarction in the last 6 months. 3. Less than 30 days since prior treatment with growth factors (EPO, G-CSF). 4. Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea. The patient must have recovered from all acute toxicities from any previous therapy. 5. Active cancer, or cancer during the year prior to trial entry other than basal cell carcinoma, or carcinoma in situ of the cervix or breast. 6. Patient already enrolled in another therapeutic trial of an investigational drug. 7. HIV infection or active hepatitis B or C. 8. Women who are or could become pregnant or who are currently breastfeeding. 9. Any medical or psychiatric contraindication that would prevent the patient from understanding and signing the informed consent form. 10. Patient eligible for allotransplantation. 11. Known allergy to SGI-110 or any of its excipients. 12. No affiliation to an insurance system.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the response rate (CR+PR+ marrow CR + HI according to IWG 2006 criteria) of the administration of SGI-110 in patients with high-risk MDS, CMML 2, and AML with 20-30% marrow blast without response after at least 6 cycles of azacitidine or decitabine (but without overt progression ie AML progression if patients had no AML at onset of azacitidine/decitabine) or doubling of marrow blast percentage between onset of azacitidine/decitabine and screening;Secondary Objective: To determine •toxicity profile and safety of the SGI-110 •response duration, time to IPSS progression, and loss of RBC transfusion independence in responders •rate of progression to AML •overall survival To study •prognostic factors of response, including IPSS-R, IPSS-karyotype and somatic mutations •the correlation between methylation profiles before and during therapy;Primary end point(s): -Number of complete Remission (CR), CR with incomplete hematological recovery (CRi), Partial Remission (PR), Marrow CR and Hematological Improvement (HI)according to IWG 2006 criteria after 6 treatment cycles ;Timepoint(s) of evaluation of this end point: The response rate will be evaluated after six cycles, according to IWG 2006 criteria. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Duration of response, measured from the date an objective response was achieved to the date of relapse or progression or the date of last contact if no event occurred. - Overall survival measured from the date of enrollment to death or the date of last contact. - Prognostic factors of response including biological correlates (mutational analysis, methylation profiles) ;Timepoint(s) of evaluation of this end point: - Duration of response - Overall survival - Prognostic factors of response | — |
Countries
Canada, France, United Kingdom, United States
Outcome results
None listed