A Phase 1/2 Study of Sequential Idarubicin + Cytarabine, Followed by Lenalidomide, in Patients With Myelodysplastic Syndrome (RAEB-2) or With Previously Untreated Acute Myeloid Leukemia
All three drugs are FDA approved to treat patients in the United States of America.
Idarubicin and Cytarabine combination therapy is a standard treatment for patients with
acute myeloid leukemia (AML). Lenalidomide is FDA approved to retreat patients with Multiple
Myeloma or Myelodysplastic syndrome with a specific change in their DNA. Loss of a specific
part of DNA is also seen in some patients with AML.
This is a phase 1/2, dose-escalation trial of Lenalidomide given in combination with
idarubicin + cytarabine. During phase 1, we will enroll patients with AML involving del
5q31; 2) patients with MDS RAEB-2 associated with monosomy 5 or segmental deletion involving
5q31, either alone or with additional cytogenetic abnormalities, and 3) older patients with
any type of karyotypic profile in whom an effective and reliable standard of care remains to
be developed. All 3 groups of patients define a population of patients with very poor
prognoses. Dose escalation of lenalidomide will use a standard 3x3 design. Dose escalation
of Lenalidomide only will take place, while the doses of idarubicin and cytarabine will be
constant. This trial will have an induction component, consolidation component, and
maintenance component. Overall safety and MTD will be determined from the induction phase
During phase 2, we will enroll only patients with AML age ≥ 60 years. During phase 2, the
efficacy of this combination of Lenalidomide + idarubicin + cytarabine, at the maximum
tolerated dose (MTD) for Lenalidomide (determined during phase 1), will be tested.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Participants With Adverse Events (AEs) - Phase I Therapy
Rates of hematologic and non-hematologic toxicities of lenalidomide following idarubicin and cytarabine as induction therapy and as consolidation therapy. For the phase 1 component, no formal statistical analysis is planned. The primary endpoint is to assess safety and determine a recommended phase 2 dose of lenalidomide given in combination with standard idarubicin + cytarabine induction therapy.
Jeffrey Lancet, M.D.
H. Lee Moffitt Cancer Center and Research Institute
United States: Institutional Review Board
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|
|Cleveland Clinic - Taussig Cancer Institute||Cleveland, Ohio 44195|