In Patients with High-Risk Myelodysplastic Syndrome who have failed Therapy with Azacitidine MedDRA version: 9.1 Level: LLT Classification code 10028533 Term: Myelodysplastic syndrome
Conditions
Interventions
Trade Name: Evoltra
Pharmaceutical Form: Intravenous infusion
Sponsors
Groupe Francophone des Myélodysplasies (GFM)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Patients aged 18 years or more with MDS according to FAB classification and intermediate-2 or high IPSS risk scores, or CMML (with WBC 10%) according to WHO classification, or AML according to WHO classification if less than 30% bone marrow blasts (RAEB-T according to FAB MDS classification) •Patients previously treated by azacitidine (Vidaza®) in proven progression, or stable after 6 courses with ongoing transfusion dependent anemia (> 4 RBC units in the 8 weeks preceding inclusion ( as erythroid response in IWG 2006 criteria is reduction of at least 4 RBC units in 8 weeks ) •Previous biological and or targeted therapies of MDS or AML are allowed if stopped more than 1 month before inclusion. 1.ECOG PS = 2. 2.Adequate renal and liver function 3.Serum creatinine = 110 microM/L in men or 90 microM/L in women. If plasma creatinine level >90- 110microM, then the estimated glomerular filtration rate (GFR) must be > 50 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease (MDRD) equation where Predicted GFR (ml/min/1.73 m2) = 32788x (plasma creatinine level (microM)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x (1.212 if patient is African American) 4.Bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: •Patients with AML and bone marrow blasts count of 20-30% , if candidates to intensive AML type chemotherapy •Known hypersensitivity to clofarabine or excipients •Concomitant malignant disease. •Active uncontrolled infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment). •Concomitant severe cardiovascular disease, i.e. congestive heart failure (NYHA grade > 3) •Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results •No affiliation to a national insurance scheme directly or to an equivalent system •Chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol. •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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The MTD is defined as the dose at which no more than one of 6 patients experience a DLT with the next higher dose having at least 2 of 3 or 2 of 6 patients experiencing a DLT. The MTD or the target dose level, whichever is attained first, will be the RD. The RD will be further confirmed by the accrual of 3 new patients and the analysis of the tolerance of repeated cycles. Definitions of DLT The dose limiting toxicity will be defined as the occurrence during the first treatment course of any of the toxicities listed below which are attributed to study drug. Toxicity grades are based on the NCI Common Terminology Criteria for Adverse Events (version 3.0). - Fifty percent drop in the absolute neutrophil count (ANC) or platelet count, compared to baseline, or lower limits of normal range (if baseline counts were above normal range) and without recovery by D56 of cycle 1 of therapy - Other non-hematologic toxicity = any other drug-related grade = 3 non-hematologic toxicity during cycle, excluding febrile neutropenia, grade 3 skin rash, = grade 3 anorexia, transient isolated elevations in hepatic transaminases or alkaline phosphatase, and nausea/vomiting, diarrhea, or mucositis that resolves (with or without supportive care) to < grade 3 within 48 hours of onset of = grade 3. Patients will be only evaluable for DLTs, if a complete first course of clofarabine (D1-5 or D1, 3, 5, 8, 10), has been administered during the phase I part of the study. From course 2 in the phase I part, and during any courses in phase II part of the study, patients may be evaluable for toxicity if related to clofarabine even after a administration of a single dose ;Main Objective: To determine the maximal tolerated dose (MTD) and dose limiting toxicities (DLTs) of increased doses of IV clofarabine administered either daily from D1 to D5 for a 28 to 56 day-course or every other day from D1 to D10 for a 28 to 56 day-course. ;Secondary Objective: To determine response rates, | — |
Countries
France
Outcome results
None listed