Phase II Trial of Lenalidomide in Older Patients (>/= 60 Years) With Untreated Acute Myeloid Leukemia Without Chromosome 5q Abnormalities
The incidence of AML increases with age, and current treatment options for the older patient
population with newly diagnosed AML (AML >= 60) is limited, all with poor outcomes. AML >=
60 patients are more likely to have poor-risk cytogenetics abnormalities, and many have a
preceding myelodysplastic syndrome (MDS). Traditional induction chemotherapy approaches in
AML with cytarabine and anthracyclines yield remissions in 45-60% of AML >= 60, however the
vast majority of these patients relapse with a median survival of about 9 months. These
patients are rarely candidates for potentially curative allogeneic stem cell
transplantation. Many untreated AML >= 60 patients are not candidates for aggressive
therapy, and those who do receive therapy have a significant induction mortality of 10-20%,
and significant hematologic toxicity occurs in over 30%, with no change in overall survival
compared with supportive care. AML >= 60 patients with favorable risk cytogenetics have a
modest improvement in prognosis, for example with a 5 year overall survival of ~20%,
compared with 0% in other cytogenetic categories. Thus, all eligible patients with AML >=
60 should be recommended a clinical trial, regardless of whether they would be offered
generally ineffective traditional induction chemotherapy. More effective and less toxic
therapies are needed for the treatment of AML in this older patient population, indeed the
preferred first line therapy in the national cancer center network (NCCN) guidelines for AML
is a clinical trial.
In trials of lenalidomide in patients with MDS the dose of lenalidomide has been reduced for
myelotoxicity and/or thrombocytopenia. However, current paradigms for the therapy of acute
myeloid leukemia are based on using high doses of myelosuppressive chemotherapy and
supporting the patient through a 4-5 weeks period of neutropenia/thrombocytopenia in an
attempt to eliminate the malignant clone. Based on its efficacy in the related myeloid
disorder MDS, and the close relationship between MDS and AML in patients > 60, this trial
employs the same paradigm of myelosuppressive therapy using high dose lenalidomide instead
of chemotherapy. Importantly, within the MDS trials using low doses of lenalidomide,
responses were observed in 3/9 (33%) of patients with excess blasts (RAEB/RAEB-t), which are
now classified as evolving into AML or AML. This suggests that the therapeutic effect of
lenalidomide occurs in the setting of a large percentage of blasts, such as AML, although
the dose and schedule of lenalidomide administration is different. The response of AML >=
60 patients to the proposed high dose lenalidomide regimen is unknown. Following high dose
lenalidomide, in those patients that have a response, we propose using a lower dose
maintenance strategy similar to the FDA approved dosing for MDS. The maintenance phase will
include standard dose reductions for unacceptable toxicities.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To assess the morphologic complete remission rate (CR) of lenalidomide therapy in this patient population
30 days, 60 days, and after 2 cycles of low dose therapy
No
Ravi Vij, M.D.
Principal Investigator
Washington University in St. Louis
United States: Food and Drug Administration
06-0907
NCT00546897
February 2007
March 2012
Name | Location |
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Washington University School of Medicine | Saint Louis, Missouri 63110 |