Myelodysplastic Syndromes Acute Myeloid Leukaemia Chronic Myelomonocytic Leukaemia MedDRA version: 14.1 Level: LLT Classification code 10054350 Term: Chronic myelomonocytic leukemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: LLT Classification code 100
Conditions
Interventions
Trade Name: Dacogen
Product Name: DECITABINE
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: DACOGEN
CAS Numb
Sponsors
King's College London
King's College Hospital NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written signed informed consent. 2. 18 years of age or older 3. At study entry, diagnosed MDS with 5% or more marrow blasts and IPSS risk intermediate 2 or high risk; or chronic myelomonocytic leukemia (CMML-2); or AML with 20-30% bone marrow blasts (previously defined as RAEB-t by the FAB MDS classification). 4. Patients who have failed therapy with azacitidine* see definition below. 5. Performance status 0-2 (ECOG scale). 6. Adequate hepatic (bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. Patients with >30% bone marrow blasts at study entry. 2. Nursing and pregnant females. 3. Women of childbearing potential (WCBP) † and males not willing to practice an effective method of contraception whilst receiving decitibine and for 2 months after the last infusion. † A woman of child-bearing potential is a sexually mature woman who has not undergone a hysterectomy or bilateral oopherectomy or who has not been naturally postmenopausal for at least 24 consecutive months (i.e., who has had menses at any time in the preceding 24 consecutive months). 4. Patients with concurrent malignancy. 5. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure and unstable angina pectoris. 6. Ongoing oral corticosteroids are not permitted. However, use of corticosteroids (topical and inhaled) is permitted and prophylactic steroids are allowed for transfusion reactions. 7. Patients who have received any investigational agent within the 30 days preceding the first dose of study drug. 8. Patients who have received prior intensive combination chemotherapy or high-dose cytarabine (>/= 1g/m*2 per dose) for the treatment of MDS or AML. (Prior biologic therapies, targeted therapies and single agent chemotherapy are allowed). 9. Patients who have an active viral or bacterial infection. Note: No patient is allowed to enter the study unless infections have been fully treated and the patient has remained afebrile for 7 days without antibiotics. 10. Patients who have concurrent autoimmune hemolytic anemia or immune thrombocytopenia. 11. Patients who have previously been treated with decitabine. 12. Patients who have known positive serology for HIV. 13. Patients with a condition that may be unable to comply with the treatment and monitoring requirements of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the overall response rate (CR+PR as per IWG 2006) at 6 months in MDS patients, CMML-2 patients, and AML patients with up to 30% bone marrow blasts (previously classified as RAEB-t by the FAB MDS classification), treated with low-dose decitabine who have previously failed therapy with 5-azacitidine. ; Secondary Objective: To assess overall survival. To assess time to AML progression or death. To assess haematological improvement. To assess transfusion requirements. To assess cytogenetics response. To assess grade 3 and 4 treatment related toxicity To assess additional cytogenic markers: DNA methylation status, markers of apoptosis, change in gene expression and Single Nucleotide Polymorphism Profiles. ; Primary end point(s): Overall Response Rate ;Timepoint(s) of evaluation of this end point: Duration of response is defined as the interval from date complete or partial remission is documented to date of recurrence/progression, death due to any cause, or lost to follow-up. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Overall survival 2) Time to AML 3) Hematologic Improvement Hematologic improvements (HI) must last at least 2 months in the absence of ongoing cytotoxic therapy). Hematologic improvement should be described by the number of individual, positively affected cell lines (e.g., HI-E; HI-E + HI-N; HI-E + HI-P + HI-N). 4) Erythroid response (HI-E) Hgb increase by 1.5 g/dL. 5) Platelet response (HI-P) Absolute increase of 30 x 109/L for patients starting with > 20 x 109/L platelets. Increase from 20 x 109/L and by at least 100%. 6) Neutrophil response (HI-N) At least 100% increase and an absolute increase > 0.5 x 109/L. 7) Transfusion requirements Transfusion requirements will be recorded for each patient for the 8-week period before first dose of study drug and during the trial. To be considered transfusion independent, patients must not have received transfusions or medications to stimulate production ofred or white blood cells or platelets for a period of 8 weeks. 8) Cytogenetic Response Rate Cytogenetic response requires 20 analyzable metaphases using conventional cytogenetic techniques. 9) Treatment Related Toxicity Toxicity will be scored using CTC Version 3.0 for toxicity and adverse event reporting. ; Timepoint(s) of evaluation of this end point: 1) Overall survival is defined as the date of first dose of study drug to the date of death from any cause. 2) Time to AML is defined as the date of the first dose of study drug to the first date that the patient is confirmed to have AML (=20% blasts in bone marrow) 3) 30 days post last dose 4) 30 days post last dose 5) 30 days post last dose 6) 30 | — |
Countries
United Kingdom
Contacts
Public ContactDepartment of Haematology
King's College Hospital
Outcome results
None listed