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

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00001567
First received: November 3, 1999
Last updated: March 3, 2008
Last verified: April 2002
  Purpose

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.


Condition Intervention Phase
Hairy Cell Leukemia
Drug: Roferon-A
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
Official Title: A Phase II Efficacy Study of Roferon-A in Hairy Cell Leukemia

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 56
Study Start Date: January 1997
Estimated Study Completion Date: April 2002
Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Age 18-70.

Patients must have morphologically identifiable hairy cells in peripheral blood and bone marrow, or tissue biopsies with at least one of the following: 1) Positive stain for the tartrate-resistant acid phosphatase 2) Electron microscopy compatible with hairy cells.

Patients must be ambulatory with an expected survival greater than 16 weeks and be willing and able to give written informed consent.

Patients must have a disease that is assessable, defined by: 1) Pancytopenia 2) Bone marrow leukemic infiltrate 3) Lymphadenopathy, splenomegaly, or hepatomegaly.

Patients must not require palliative chemotherapy, immunotherapy or hormonal therapy other than the treatment prescribed in this protocol.

Patients must be tested for Hepatitis B surface antigen within one week of entry into this study.

No pregnant or lactating women. No fertile men and women, unless using effective contraception.

No patients with unstable angina. Patients with Class III or IV cardiovascular disease may be entered only after medical clearance by a cardiology consultant.

No patients with severe intercurrent infection or patients having had surgery within the past four weeks unless fully recovered.

No patients with impaired renal function (serum creatinine greater than 1.8).

No patients with impaired hepatic function (total bilirubin greater than 1.4).

No patients with serum calcium greater than 12 mg/dl.

No patients with a performance status less than or equal to 60% on the Karnofsky scale.

No patients who have had any prior (leukocyte or fibroblast) interferon therapy.

No patients unable to carry out the treatment program.

No patients less than 20,000 per cu mm platelets and clinical bleeding disorder; both must be present for patient to be excluded.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001567

Locations
United States, Maryland
National Cancer Institute (NCI)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00001567     History of Changes
Other Study ID Numbers: 970060, 97-C-0060
Study First Received: November 3, 1999
Last Updated: March 3, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Follow-Up Study
Relapse-Free Survival
Serum Soluble IL-2 Receptor
Hematologic Malignancy
Chronic Therapy

Additional relevant MeSH terms:
Leukemia
Leukemia, Hairy Cell
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Interferon-alpha
Anti-Infective Agents
Antiviral Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 23, 2014