Acute Myelogenous Leukemia, Myelodysplastic Syndromes
Conditions
Keywords
monosomy 5, del5q, lenalidomide, azacitidine
Brief 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.
Detailed description
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.
Interventions
DRUGAzacitidine
75 mg/m² SC days 1-5 every 28 days for a maximum of 8 cycles
DRUGLenalidomide
10 - 25 mg PO days 6-19 every 28 days for a maximum of 8 cycles
Sponsors
Celgene Corporation
Technische Universität Dresden
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose (MTD) of Revlimid® (lenalidomide)in combination with Vidaza®(5-azacitidine) | during first cycle of therapy |
Secondary
| Measure | Time frame |
|---|---|
| Clinical and cytogenetic response | during therapy |
| Safety (type, frequency, severity, and relationship of adverse events to study treatment) | during therapy |
Countries
Germany
Outcome results
None listed