AZALE: Combination of 5-azacitidine and Lenalidomide in Myelodysplastic Syndromes (MDS) or Acute Myelogenous Leukemia (AML) Myelodysplastic Syndromes
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Azacitidine and Lenalidomide Azacitidine 75 mg/m² SC days 1-5 every 28 days for a maximum of 8 cycles and Lenalidomide 10 - 25 mg PO days 6-19 every 28 days for a maximum of 8 cycles |
Drug: Azacitidine
75 mg/m² SC days 1-5 every 28 days for a maximum of 8 cycles
Other Names:
Drug: Lenalidomide
10 - 25 mg PO days 6-19 every 28 days for a maximum of 8 cycles
Other Names:
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Outcome Measures
Primary Outcome Measures
- Maximum tolerated dose (MTD) of Revlimid® (lenalidomide)in combination with Vidaza®(5-azacitidine) [during first cycle of therapy]
Secondary Outcome Measures
- Clinical and cytogenetic response [during therapy]
- Safety (type, frequency, severity, and relationship of adverse events to study treatment) [during therapy]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Understand and voluntarily sign an informed consent form.
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Age >=18 years at the time of signing the informed consent form.
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Able to adhere to the study visit schedule and other protocol requirements.
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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
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Not eligible for an immediate allogeneic HSCT (due to donor unavailability)
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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.
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Non-hematological toxicity (except alopecia) resulting from previous treatment must be resolved to WHO CTC Grade ≤ 2.
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ECOG performance status of < 3 at study entry.
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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
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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:
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Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
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Pregnant or breast feeding females. (Lactating females must agree not to breast feed while on study).
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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.
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Known hypersensitivity to thalidomide, lenalidomide, 5-azacitidine or mannitol.
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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.
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The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
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Uncontrolled lung disease.
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Known positive for HIV or acute infectious hepatitis, type A, B or C.
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Participation in another clinical study in the 4 weeks prior to enrollment or during this study.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Medizinische Klinik und Poliklinik I, Uniklinik | Dresden | Germany | ||
2 | Universitätsklinikum Düsseldorf, Klinik für Hämatologie/Onkologie/klinische Immunologie | Düsseldorf | Germany | 40225 | |
3 | Klinikum der J.W. Goethe-Universität, Medizinische Klink II | Frankfurt | Germany | 60590 | |
4 | Technische Universität München, Klinikum Rechts der Isar | München | Germany | 81675 |
Sponsors and Collaborators
- Technische Universität Dresden
- Celgene Corporation
Investigators
- Principal Investigator: Uwe Platzbecker, MD, Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TUD-AZALE1-037