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.