Clinical trial NCT01442714
Conditions: Leukemia Acute Myeloid Leukemia (AML) Myelodysplastic Syndromes (MDS)
Sponsor: Stanford University
Start date: 2011-08-01; Completion date: 2014-05-01
Enrollment: 33 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of the trial is to study how the elderly patients who have previously undergone treatment for acute myeloid leukemia and high-rRisk myelodysplastic syndromes, respond to a combined treatment with azacitidine and lenalidomide.

Detailed description:
This is an open label, single-center, and phase 2 study of the combination of azacitidine with lenalidomide in previously treated elderly patients with acute myeloid leukemia (AML) and/or high-risk myelodysplastic syndrome (MDS) who have failed prior therapy with either a demethylating agent and/or IMIDs. MDS includes Chronic Myeloid Leukemia (CML).

Participants patients will receive azacitidine on the first 7 days followed by lenalidomide. Disease assessments with bone marrow examinations will be performed and if a complete response (CR); Complete remission with incomplete count recovery (CRi); partial response (PR); or stable disease (SD) is documented after 6 total cycles, participants will continue treatment until evidence of disease progression, provided they are tolerating treatment. Participants who have progressive disease or relapsed disease after the 6th cycle will be taken off the study, and participants with excessive toxicity at any time will be taken off the study.

* CR = Less than 5% blasts with no Auer rods, absence of extramedullary disease, absolute neutrophil count (ANC) \> 1000/µL, platelets \> 100,000/µL, and independence of red cell transfusion)
* CR with incomplete recovery (CRi) = all criteria of a CR with the exception of a platelet count less than 100,000/µL or residual neutropenia (\< 1000/µL).
* PR = Meeting all hematologic criteria for CR with an allowance for 5% to 25% bone marrow blasts or decrease of pretreatment bone marrow blast percentage by ≥ 50%.
* SD = Change in bone marrow aspirate blast count within 10% of baseline.
* PD = Progressive / relapsed disease defined as reappearance of blasts in the blood or bone marrow blasts ≥ 5%, and development of extramedullary disease.

Arms: arm 1: Patients will receive a single dose of azacitidine 75 mg/m² SC or IV on days 1 to 7, followed by lenalidomide 50 mg PO daily on days 8 to 28 of a 42-day cycle.
Interventions: intervention 1: Azacitidine intervention 2: Lenalidomide
Intervention descriptions: intervention 1: Azacitidine is a chemical analogue of the cytosine nucleoside used in DNA and RNA. Azacitidine is thought to induce antineoplastic activity via two mechanisms; inhibition of DNA methyltransferase at low doses, causing hypomethylation of DNA, and direct cytotoxicity in abnormal hematopoietic cells in the bone marrow through its incorporation into DNA and RNA at high doses, resulting in cell death intervention 2: Lenalidomide has been used to successfully treat both inflammatory disorders and cancers. In vitro, lenalidomide has three main activities: direct anti-tumor effect, inhibition of angiogenesis, and immunomodulatory role. In vivo, lenalidomide induces tumor cell apoptosis directly and indirectly by inhibition of bone marrow stromal cell support, by anti-angiogenic and anti-osteoclastogenic effects, and by immunomodulatory activity.

Protocol documents: