combination of 5-azacitidine and lenalidomide in myelodysplastic syndromes (mds) or acute myelogenous leukemia (aml) myelodysplastic syndromes

Conditions: Myelodysplastic Syndromes; Acute Myelogenous Leukemia

Summary: the hypothesis of this study is that 5-aza and lenalidomide act synergistically in mds and aml patients with chromosomal abnormalities involving monosomy 5 or del5q. therefore, this phase i study will investigate the maximum tolerated dose (mtd) of lenalidomide in combination with a fixed dose of 5-aza in this patient population.

cytogenetics are the main predictors of outcome in patients with aml. in fact, a monosomy 5 or del (5q) as single aberration are poor prognostic markers. overall, the complete response rate for conventionally treated patients with newly-diagnosed aml with chromosome 5 abnormalities is about 31% to 37 % and all patients rapidly relapse if not rescued by allogeneic hsct. the situation is almost similar in patients with high-risk mds.vidaza® has been shown in clinical trials to achieve remission rates in about 29% (cr+pr) of the patients while a total of 49% achieve improvement of blood counts.revlimid® is also able to achieve complete remissions in advanced mds and even overt leukemia with or without chromosome 5 abnormalities. nevertheless, response rates are lower compared to low-risk mds (ipss low/int-1). therefore, revlimid® seems to be too weak as a single agent, but a promising compound for a combination therapy.

Eligibility criteria:
inclusion criteria: * understand and voluntarily sign an informed consent form. * age \>=18 years at the time of signing the informed consent form. * able to adhere to the study visit schedule and other protocol requirements. * relapsed or refractory aml (\>30% blasts, fab classification)with karyotype abnormalities involving monosomy 5 or del(5q) or mds and t-mds int-2 or high according to ipss classification with karyotype abnormalities involving monosomy 5 or del(5q) either previously treated or untreated * not eligible for an immediate allogeneic hsct (due to donor unavailability) * all previous mds or aml specific therapy with exception of corticosteroids not exceeding doses of 10mg/day prednisone must have been discontinued at least 1 week prior to study enrollment. * non-hematological toxicity (except alopecia) resulting from previous treatment must be resolved to who ctc grade ≤ 2. * ecog performance status of \< 3 at study entry. * laboratory test results within these ranges:serum creatinine \<= 2.0 mg/dl, total bilirubin \<= 3 x uln, ast (sgot) and alt (sgpt) \<= 3 x uln * females of childbearing potential must agree to use a reliable form of contraception or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study. exclusion criteria: * any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. * pregnant or breast feeding females. (lactating females must agree not to breast feed while on study). * any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. * known hypersensitivity to thalidomide, lenalidomide, 5-azacitidine or mannitol. * myocardial infarction within 6 months before study entry, new york heart association class iii or iv heart failure, uncontrolled angina or severe uncontrolled ventricular arrhythmias. * the development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs. * uncontrolled lung disease. * known positive for hiv or acute infectious hepatitis, type a, b or c. * participation in another clinical study in the 4 weeks prior to enrollment or during this study.

Keywords: monosomy 5 del5q lenalidomide azacitidine