Zidovudine, Interferon Alfa-2b, PEG-Interferon Alfa-2b in Patients With HTLV-I Associated Adult T-Cell Leukemia/Lymphoma
Lymphoma, Precancerous/Nonmalignant Condition
About this trial
This is an interventional treatment trial for Lymphoma focused on measuring recurrent adult T-cell leukemia/lymphoma, stage I adult T-cell leukemia/lymphoma, stage II adult T-cell leukemia/lymphoma, stage III adult T-cell leukemia/lymphoma, stage IV adult T-cell leukemia/lymphoma, HTLV-1 infection
Eligibility Criteria
Inclusion Criteria
- Any stage, histologically or cytological documented adult T-cell leukemia/lymphoma (ATLL), leukemic types only (smoldering, chronic or acute). See Appendix I for definitions of the clinical subtypes.
- Patients who have received prior treatment, including zidovudine and/or IFN, are eligible, provided that zidovudine/IFN therapy did not result in progressive disease.
- Documented HTLV-I infection: documentation may be serologic assay (ELISA, Western blot) and confirmed to be HTLV-I rather than HTLV-2 by differential Western blot (e.g., Genelabs Diagnostics HTLV Blot 2.4) or PCR.
- Measurable or evaluable disease.
- Age 18 or older.
- Karnofsky performance status ≥ 50%.
Patients must have adequate end organ and bone marrow function as defined below:
- Absolute neutrophil count ≥ 1,000 cells/mm3 and platelets ≥ 50,000 cells/mm3 unless cytopenias are secondary to ATLL.
- Adequate hepatic function: (transaminase ≤ 7 times the upper limit of normal, total bilirubin < 2.0), unless secondary to hepatic infiltration with lymphoma. If the elevated bilirubin is felt to be secondary to Indinavir or Atazavinir therapy (anti-HIV medications), patients will be allowed to enroll on protocol if the total bilirubin is ≤ 3.5 mg/dl provided that the direct bilirubin is normal.
- Creatinine < 2.0 unless due to lymphomatous infiltration.
- Patients who are HIV+ are also eligible.
- Females with childbearing potential must have a negative serum pregnancy test within 72 hours of entering into the study. Males and females must agree to use adequate birth control if conception is possible during the study. Women must avoid pregnancy and men avoid fathering children while in the study.
- Able to give consent.
- Patients already receiving erythropoietin or granulocyte-colony stimulating factor (G-CSF) are eligible.
Exclusion Criteria
- Concurrent active malignancies, with the exception of in situ carcinoma of the cervix, non-metastatic, non-melanomatous skin cancer, or Kaposi's sarcoma not requiring systemic chemotherapy.
- Grade 3 or 4 cardiac failure and/or ejection fraction < 50%.
- Psychological, familial, sociological or geographical conditions that do not permit treatment and/or medical follow-up required to comply with the study protocol.
- Patients may not be receiving any other investigational agents.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant or breast-feeding women.
- Hypersensitivity to interferon alpha-2b, peginterferon alpha-2b, zidovudine or any component of the formulation
- Autoimmune or viral hepatitis or decompensated liver disease unless due to lymphoma.
Sites / Locations
- University of Miami Sylvester Comprehensive Cancer Center - Miami
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
Induction (Up to Day 21)
Part 1 Maintenance (Up to Day 60)
Part 2A Maintenance (Up to 12 Months)
Part 2B Maintenance (Up to 12 Months)
For one cycle, up to Day 21. All participants are enrolled to induction therapy phase, then move to the maintenance therapy phase if they achieve complete response (PR) or partial response (PR). Participants who achieve a clinical CR at Day 14 response assessment will go on to Part 1 maintenance therapy. Patients who achieve a PR will receive 7 more days of induction therapy and then go on to Part 1 Maintenance Therapy.: Zidovudine: Days 1-2: 1.5 grams intravenously (IV) twice daily Days 3-21: 1.5 grams IV twice daily Interferon alfa-2b (IFN): 5 10 million units (mu) intravenously twice daily
From Treatment Day 14 or 21 to start of Month 3 (Day 60). Study participants move on to Part 1 Maintenance Therapy only if they achieve complete response (CR) or partial response (PR) after induction therapy. Restaging and molecular evaluation of disease at start of Month 3: Zidovudine: 600 mg orally twice daily in all phases of Maintenance Therapy PEG-Interferon alfa-2b: 1.5 ug/kg subcutaneously (SQ) once weekly Participants then proceed to Part 2 maintenance.
Participants achieving a CR with undetectable clonal disease. Participants will receive therapy for as long as response is maintained: Zidovudine: 600 mg orally twice daily PEG-Interferon alfa-2b: 1.5 ug/kg subcutaneously (SQ) once weekly
Participants achieving a CR with minimal residual disease (by multiplex PCR) or PR in Part 1: Zidovudine: 600 mg or 300 mg orally twice daily, per protocol PEG-Interferon alfa-2b: 1.5 ug/kg subcutaneously (SQ) once weekly, per protocol Valproic acid, 250 mg orally twice daily, per protocol