A Phase II Efficacy Study of Roferon-A in Hairy Cell Leukemia
Status:
Completed
Trial end date:
2002-04-01
Target enrollment:
Participant gender:
Summary
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 uniformly disease progression
requiring reinstitution of therapy was observed. There appear 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
suggests 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 three million units subcutaneously 3 times per week. Responding
patients have continued on therapy indefinitely.