A Phase 1 Study of Lenalidomide in Combination with Mitoxantrone, Etoposide, and Ara-C in Patients with Relapsed or Refractory Acute Myeloid Leukemia

• Published in: Blood 2015-12, Vol.126 (23), p.2550-2550
• Main Authors: DeAngelo, Daniel J., Fathi, Amir T., Werner, Lillian, Avigan, David, Luptakova, Katarina, Wadleigh, Martha, Steensma, David P., Hobbs, Gabriela Soriano, Attar, Eyal C., Amrein, Philip C., Stone, Richard M., Ballen, Karen K.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V126.23.2550.2550

Background: The prognosis for patients with relapsed acute myeloid leukemia (AML) remains extremely poor. Standard reinduction regimens, such as mitoxantrone, etoposide, and ara-C (MEC), have been associated with complete remission rates in the 23 to 30% range. Lenalidomide (Len), an immunomodulatory drug, has efficacy in relapsed AML and has been shown to augment the effects of standard chemotherapies (anthracyclines and ara-C) in preclinical AML studies. These data prompted the current phase 1 study of Len in combination with MEC in pts with relapsed AML. Methods: The trial included pts (≥ 18 yrs) with relapsed or refractory AML. The primary objective was determination of the maximum tolerated dose (MTD) of Len when given in combination with MEC. Secondary objectives included safety, efficacy and time to count recovery. The study examined escalating doses (5-10 mg) of Len given daily for the first 14 days in combination with standard MEC doses of mitoxantrone (8 mg/m2/d), etoposide (100 mg/m2/d), and ara-C (1000 mg/m2/d) on days 4 through 8. Due to observations of prolonged count recovery, the Len dosing schedule was amended by reducing the duration of treatment to 10 days starting on Day 1. The dose of len was then re-escalated starting at 5 mg/d (5-10-25-50). A standard 3+3 dose-escalation design was used. Dose limiting toxicity was defined as Grade IV rash or Grade IV neuropathy during the first 28 day period, or delayed neutrophil (ANC