WASHINGTONThe National Cancer Institute will expand its
support for trials of imatinib mesylate (Gleevec, also known as STI-571),
recently approved for use in chronic myeloid leukemia (CML), to explore the
drug’s potential in several other types of malignancies, director Richard
D. Klausner, MD, told the National Cancer Advisory Board (NCAB).
Gleevec blocks the functioning of Bcr-Abl, an abnormal
protein that results from a reciprocal translocation between chromosomes 9
and 12the Philadelphia chromosomeand causes CML. Im-atinib also
inhibits c-kit and PDG-F, two additional proteins linked to a number of
Three NCI-sponsored studies are currently enrolling
patients. A phase III randomized trial is comparing two different imatinib
doses in patients with CD117-expressed metastatic or unresectable
gastrointestinal stromal tumor (GIST). Its protocol calls for enrolling 600
patients age 15 and older within 2 years.
At the American Society of Clinical Oncology (ASCO) meeting
in May, Charles D. Blanke, MD, of the Oregon University Health Sciences
Center, reported results from a phase II trial of 148 GIST patients treated
with imatinib. The results showed an 85% tumor control rate: 59% partial
response and 26% stable disease.
The second active imatinib trial is a phase I/II brain tumor
study in patients age 18 and older. The study will enroll 36 patients with
recurrent malignant glioma or meningioma in a phase I trial. The phase II
trial will accrue between 40 and 60 glioma patients.
Finally, a phase I imatinib study is enrolling patients
under age 22 with recurrent Ph-chromosome-positive leukemia (ALL, AML, CML).
NCI will also support three phase I/II studies that are
approved but not yet active. One will determine the safety of imatinib
combined with daunorubicin, vincristine, and prednisone in patients age 18
and older with blastic-phase CML or Ph-chromosome-positive acute lymphocytic
A second will test the maximum tolerated dose of
interferon-alfa administered with imatinib in 15 to 40 patients age 18 and
older with newly diagnosed or interferon refractory or resistant chronic
phase CML. Researchers will also enroll up to 32 patients age 18 and older
with blastic-phase CML in a study to determine the maximum tolerated dose of
high-dose cytarabine combined with imatinib.
Protocol abstracts of the active and approved imatinib
trials can be found at http://cnetdb.nci.nih.gov.