Trial Information

A Phase II Efficacy Study of Roferon-A in Hairy Cell Leukemia

This study began as an efficacy study of interferon alpha-2a in patients with hairy cell
leukemia. It was observed that most patients responded with interferon, but that very few
complete responses were being obtained. Studies being done elsewhere confirmed the low
complete remission rate. Once interferon was stopped, nearly uniform disease progression
requiring reinstitution of therapy was observed. There appears to be very few if any
patients who will not require further therapy after receiving 12 or 18 months of continuous
interferon treatment. Because of these findings, and in order to evaluate the safety and
efficacy of long-term recombinant interferon-alpha (IFN-Alpha) in patients with hairy cell
leukemia, we opted to administer interferon continuously to patients who were initially
responsive to this drug. Of the 53 evaluable patients (of the 56 entered on this study),
there was one complete remission, 41 partial remissions, 1 minor response, 9 patients with
stable disease and only 1 patient with disease progression. Fourteen patients continue to
receive interferon without interruption with a median duration of continuous interferon
treatment of 9.2 years. Thirty-four patients discontinued interferon for a variety of
reasons, the most common being the development of acquired interferon resistance in
association with interferon antibodies. The resistance to interferon was manifested early,
in the first 18 months of treatment, except in two cases. An important finding in this
study is the continued slow, but significant, hematologic improvement in absolute
granulocyte and platelet counts beyond 18 months of therapy, thereby indicating that
prolonged treatment results in continued benefit rather than the production of antibodies
with subsequent development of interferon resistance. Although it is clear from this study
that hairy cell leukemia can be controlled in the long-term with interferon, longer
follow-up will be necessary to determine if continuous therapy with interferon is better
than intermittent therapy. The optimal therapy for hairy cell leukemia remains open to
discussion. Although early reports suggested that 2-chlorodeoxyadenosine was curative,
additional studies with longer periods of follow up suggest that as many as 30% of patients
will relapse. This study provides the only instance where continuous long term treatment
with interferon has been evaluated. This provides an opportunity to evaluate the long term
toxicity of chronic interferon therapy, the long term efficacy of this treatment and to
evaluate the potential benefits of long term interferon in preventing second malignancies, a
complication noted in about 15% of patients treated in other fashions.

After their initial clinical evaluation, patients were given 3 million units of recombinant
IFN-Alpha subcutaneously daily for 4 to 6 months. In responding patients, maintenance
therapy was given at a dose of 3 million units subcutaneously 3 times per week. Responding
patients have continued on therapy indefinitely.