Genetics Institute, Inc. announced positive results of a phase
II study of recombinant human interleukin-eleven (rhIL-11). In
the study, rhIL-11 restored platelets in thrombocytopenic patients
undergoing cancer chemotherapy to the extent that significantly
fewer patients required platelet transfusions when compared to
patients on placebo.
Based on this favorable outcome, Genetics Institute said that
it plans to begin a phase III study of rhIL-11 by the end of 1995.
In addition, the company expects to have results from two additional
phase II studies later this year.
"We are extremely pleased with the results of this study,"
said Patrick Gage, PhD, Chief Operating Officer for Genetics Institute.
"We have now completed a rigorous, 'real world' test of rhIL-11
in patients who, on entry into the study, were already platelet
transfusion-dependent and were being treated with a wide variety
of chemotherapy regimens. Despite these challenges, rhIL-11 achieved
a statistically significant outcome for a meaningful clinical
endpoint--eliminating platelet transfusions. Our goal now is to
proceed expeditiously to a phase III study and, assuming continued
positive results, complete the regulatory review process to make
this highly promising product available to physicians and patients."
In the double-blind, randomized, placebo-controlled study, involving
more than 80 patients from 20 medical centers, 30% of the patients
who received a daily 50- mcg/kg dose of rhIL-11 did not require
a platelet transfusion. These results were statistically significant
when compared to the placebo group, of which only 4% avoided platelet
transfusions. Of the patients who received a daily 25-mcg/kg dose,
18% also did not require a platelet transfusion, suggesting a
dose-response relationship for rhIL-11 in this study. In addition,
the rhIL-1-treated patients who did have to be transfused showed
a trend toward requiring fewer transfusions than those on placebo.
Study investigator Michael Gordon, MD, Director, Clinical Cytokine
Program, Indiana University Medical Center, Indianapolis, who
also studied rhIL-11 in phase I trials, said: "This study
significantly advances our knowledge of ways to reduce platelet
transfusions, a key concern for patients being treated with dose-intensive
chemotherapy. If similar results are demonstrated in phase III
studies, rhIL-11 therapy could lead to better treatments for cancer
patients, reduce the risks associated with platelet transfusions,
and offer the potential to conserve healthcare resources."
"This phase II study is important because it is a double-blind,
randomized, placebo-controlled trial and it clearly shows promising
results in a very difficult patient population at risk for thrombocytopenia,"
commented another study investigator, Joseph Moore, MD, of Duke
University Medical Center.
In the study, the patients had a wide range of solid tumors or
lymphomas and were being treated with a variety of chemotherapy
regimens. All patients were treated on an outpatient basis. Treatment
with rhIL-11 was administered by subcutaneous injection.
In general, rhIL-11 was well-tolerated by the study patients.
The side effects profile was similar to that observed in phase
I studies, and included mild constitutional complaints and symptoms
believed to be related to fluid retention, including a low incidence
of transient atrial arrhythmias. These effects were reversed when
the treatment was completed or discontinued, and caused no significant
clinical consequences. In addition, rhIL-11 treatment was not
associated with an increased incidence of neutropenic fevers,
which has been seen with several other cytokines.