MYELODYSPLASTIC SYNDROMES MedDRA version: 18.0 Level: LLT Classification code 10028534 Term: Myelodysplastic syndrome NOS System Organ Class: 100000004864
Conditions
Interventions
Trade Name: EXJADE®
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: DEFERASIROX
CAS Number: 201530-41-8
Current Sponsor code: ICL670
Other descriptive name: EXJADE
Concentration unit: mg/
Sponsors
CHU-ULg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Myelodysplastic Syndrome intermediate II and high risk according to the IPSS, non-proliferative chronic myelomonocytic leukemia (CMML) (leukocytes 4.0 mEq/L and magnesium > 75 mEq/L); 7.Patient ineligible for allogeneic hematopoietic stem cell transplantation; 8.Adherence to the study visit Schedule; 9.Women of childbearing potential must: Agree to use effective contraception without interruption throughout the study and for a further 3 months after the end of treatment; 10. 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 3 months after the end of treatment if their partner is of childbearing potential. Agree to learn about the procedures for preservation of sperm. 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 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: 1.Severe infection or any other uncontrolled severe condition 2.Less than 30 days since prior treatment with growth factors (EPO, G-CSF) or non-cytotoxic agents (including low-dose oral chemotherapy)i in the event of prior treatment with cytotoxic or demethylating agents, an interval of 3 months is required; 3.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; 4.History of urinary calculi; 5.Uncontrolled primary hyperparathyroidis; 6.Hypercalcemia and/or hypophosphatemia, hypervitaminosis D; 7.Patient already enrolled in another therapeutic trial of an investigational drug; 8.HIV infection or active hepatitis B or C; 9.Women who are or could become pregnant, or who are currently breastfeeding; 10.Any medical or psychiatric contraindication that would prevent the patient from understanding and signing the informed consent form; 11.Ferritin < 300 ng/mL.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I To determine the safety of the deferasinox-vitaminD-azacitidine comination in the treatment of high-risk MDS Phase II To evaluate the response rate (CR, PR, marrow CR, according to IWG 2006 criteria);Secondary Objective: Clinical part, to determine: -the duration of the response -overall survival -the safety profile Biological studies: -Pre-treatment assessment; incidence of vitamin D deficiency and iron overload in MDS -To monitor the safety of the combination iron work up; vitamin D level, renal function, phosphorus/calcium work up. -To assess the correction of cytopenias and other effects on the complete blood count (elevation of circulating monocytes, blast counts) -To establish pre-treatment tests that would predict the clinical response. -To understand the mechanisms underlying efficacy, any resistance and secondary treatment failure.;Primary end point(s): Phase I: Safety of the deferasirox-vitamin D combination and of azacitidine. It will be analyzed after 2 cycles, and the decision to continue to the dose level above and to enroll 20 phase II patients (10 patients per group) will be taken after assessment of the first patients enrolled by an independent data monitoring committee (IDMC), in association with the investigators. -Phase II: number of complete responses (CR) + partial responses (PR) according to IWG 2006 criteria .;Timepoint(s) of evaluation of this end point: Phase I: Toxicity, evaluated using NCI-CTCAE V3.0 criteria. All patients who have received at least one cycle will be considered evaluable for response. Phase II: response, according to IWG 2006 criteria. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Total percentage of responses, including all patients achieving CR, PR, marrow CR or hematologic improvement, evaluated according to IWG 2006 criteria after 3 and 6 treatment cycles. -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. -Biological assessment ;Timepoint(s) of evaluation of this end point: to determine -the duration of the response -overall survival -the safety profile | — |
Countries
Belgium
Contacts
Public ContactJo Caers
CHU-ULg
Outcome results
None listed