Zidovudine, Interferon Alfa-2b, PEG-Interferon Alfa-2b in Patients With HTLV-I Associated Adult T-Cell Leukemia/Lymphoma

NCT ID: NCT00854581

Last Updated: 2018-04-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2011-11-30

Brief Summary

RATIONALE: Human T-cell lymphotropic virus type 1 (HTLV-1) can cause cancer. Zidovudine is an antiviral drug that acts against the human T-cell lymphotropic virus type 1. Giving zidovudine, interferon alfa-2b, and PEG-interferon alfa-2b together may stimulate the immune system and slow down or keep the cancer cell from growing.

PURPOSE: This clinical trial is studying how well giving zidovudine together with interferon alfa-2b and PEG-interferon alfa-2b works in treating patients with human T-cell lymphotropic virus type 1-associated adult T-cell leukemia/lymphoma.

Detailed Description

OUTLINE: This is a multicenter study.

• Induction therapy: Patients receive zidovudine IV twice daily on days 1-14, and recombinant interferon alfa-2b IV twice daily on days 3-14. Patients achieving clinical complete response (CR) proceed to part 1 maintenance therapy; patients achieving partial response (PR) receive another 7 days of zidovudine and recombinant interferon alfa-2b and then proceed to part 1 maintenance therapy.
• Part 1 maintenance therapy: Patients receive oral zidovudine twice daily and PEG-interferon alfa-2b subcutaneously (SC) once weekly, beginning on day 14 or 21 and continue to day 60. Patients are evaluated after completion of part 1 maintenance therapy and proceed to part 2 maintenance therapy.
• Part 2 maintenance therapy: Patients achieving CR with undetectable clonal disease proceed to group A; patients achieving CR with minimal residual disease (by PCR) or PR proceed to group B.

• Group A: Patients receive oral zidovudine twice daily and PEG-interferon alfa-2b SC once weekly. Treatment continues in the absence of disease progression or unacceptable toxicity.
• Group B: Patients receive oral zidovudine twice daily and PEG-interferon alfa-2b SC once weekly for 12 weeks and undergo reevaluation. Patients in continued CR with minimal residual disease or stable PR receive oral valproic acid twice daily, PEG-interferon alfa-2b SC once weekly, and oral zidovudine twice daily for 6 months. At that point (month 9) patients with no detectable clonal disease continue their previous treatment, while patients with minimal residual disease receive PEG-interferon alfa-2b SC and oral zidovudine twice daily in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline, days 1 and 2, and months 3, 6, and 12 for protein, genomic DNA, and RNA analysis. Baseline molecular characteristics of the tumor and tumor response to treatment is assessed.

After completion of study treatment, patients are followed every 3 months for 1 year.

Conditions

Lymphoma; Precancerous/Nonmalignant Condition

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Induction (Up to Day 21)

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

Group Type: EXPERIMENTAL

Interferon alfa-2b

Intervention Type: BIOLOGICAL

Administered intravenously.

Zidovudine

Intervention Type: DRUG

Administered intravenously during Induction Therapy; orally during Maintenance Therapy in all Phases (1, 2A and 2B).

Part 1 Maintenance (Up to Day 60)

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.

Group Type: EXPERIMENTAL

PEG-interferon alfa-2b

Intervention Type: BIOLOGICAL

Administered subcutaneously.

Zidovudine

Intervention Type: DRUG

Administered intravenously during Induction Therapy; orally during Maintenance Therapy in all Phases (1, 2A and 2B).

Part 2A Maintenance (Up to 12 Months)

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

Group Type: EXPERIMENTAL

PEG-interferon alfa-2b

Intervention Type: BIOLOGICAL

Administered subcutaneously.

Zidovudine

Intervention Type: DRUG

Administered intravenously during Induction Therapy; orally during Maintenance Therapy in all Phases (1, 2A and 2B).

Part 2B Maintenance (Up to 12 Months)

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

Group Type: EXPERIMENTAL

PEG-interferon alfa-2b

Intervention Type: BIOLOGICAL

Administered subcutaneously.

Valproic Acid

Intervention Type: DRUG

Administered orally.

Zidovudine

Intervention Type: DRUG

Administered intravenously during Induction Therapy; orally during Maintenance Therapy in all Phases (1, 2A and 2B).

Interventions

PEG-interferon alfa-2b

Administered subcutaneously.

Intervention Type: BIOLOGICAL

Interferon alfa-2b

Administered intravenously.

Intervention Type: BIOLOGICAL

Valproic Acid

Administered orally.

Intervention Type: DRUG

Zidovudine

Administered intravenously during Induction Therapy; orally during Maintenance Therapy in all Phases (1, 2A and 2B).

Intervention Type: DRUG

Other Intervention Names

PEG-IFN-alfa2b; Depakene; Retrovir; AZT

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Miami

OTHER

Sponsor Role: lead

Responsible Party

Juan C. Ramos

Associate Professor of Clinical

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Juan Carlos Ramos, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, United States

Countries

United States

Other Identifiers

SCCC-2007055

Identifier Type: OTHER

Identifier Source: secondary_id

5P01CA128115-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

20070805

Identifier Type: -

Identifier Source: org_study_id