Clinical trial NCT00854581
Conditions: Lymphoma Precancerous/Nonmalignant Condition
Keywords: 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
Sponsor: University of Miami
Start date: 2007-11-01; Completion date: 2011-11-01
Enrollment: 13 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

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.

Arms: arm 1: 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 arm 2: 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. arm 3: 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 arm 4: 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
Interventions: intervention 1: PEG-interferon alfa-2b intervention 2: Interferon alfa-2b intervention 3: Valproic Acid intervention 4: Zidovudine
Intervention descriptions: intervention 1: Administered subcutaneously. intervention 2: Administered intravenously. intervention 3: Administered orally. intervention 4: Administered intravenously during Induction Therapy; orally during Maintenance Therapy in all Phases (1, 2A and 2B).

Protocol documents: