Phase I/II Trial Evaluating the Safety and Efficacy of Ruxolitinib in Subjects With Smoldering and Chronic Adult T-cell Leukemia (ATL)

Background:

• The human T-cell leukemia virus 1 (HTLV-1) causes adult T-cell leukemia (ATL). Infection does not immediately cause ATL, but it can develop over time. ATL is a rare and aggressive type of cancer that disrupts the body's ability to control the HTLV-1 virus. Infected T lymphocytes that are transformed by HTLV-1 into malignant ATL cell have constitutively activated Interleukin-2 (IL-2), IL-9 and IL-15 production pathways that function as autocrine and paracrine stimulators of these cells by stimulating these cells through the Janus Kinase (JAK) 1 and 3/Signal transducer and activator of transcription 5 (STAT5) pathways.
• Ruxolitinib is a drug that has been approved to treat bone marrow disorders. Ruxolitinib is a tyrosine kinase inhibitor that disrupts signaling through the JAK 1 and 2/STAT3 and 5 pathways and have potential as a treatment for ATL. Researchers want to see if ruxolitinib can be a safe and effective treatment for ATL.
• Initially this trial was designed as a single dose level phase II trial with ruxolitinib given at the dose approved for the treatment of primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis.
• Clinical and correlative laboratory data demonstrated limited inhibition and impact on the subject's disease with the standard 20 mg twice daily dose. Given that the manufacturers of ruxolitinib had safety data for administering ruxolitinib to normal healthy volunteers at doses up to 50 mg twice or 100 mg once daily, the trial was reconfigured as a phase I dose escalation trial giving these higher doses on the twice daily schedule

Objectives:

Initial Phase II design:

• Define clinical or objective response rate for the 20 mg twice daily dose of Ruxolitinib.
• Define safety profile, Time to progression and survival time.

Subsequent Phase I dose escalation with expansion cohort treated at the MTD or MAD:

• Determine the maximum tolerated dose (MTD) and clinical response rate for ruxolitinib administered at the higher dose levels.
• Determine safety profile, time to progression
• To test the safety and effectiveness of ruxolitinib for adult T-cell leukemia.

Eligibility:

• Individuals at least 18 years of age who have ATL caused by HTLV-1.

Design:

• Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies will also be performed.
• Participants will take ruxolitinib twice a day for 28 days. They will have blood tests on days 1, 14, and 28. These tests will look at the levels of HTLV-1 in the blood. Participants will have a final blood test about 2 weeks later. Treatment will also be monitored with imaging studies.
• Participants who have a partial response during treatment may be able to start taking ruxolitinib again after the final blood test. They will continue to take ruxolitinib for as long as it is effective and the side effects are not severe.
• Participants who have a full response during treatment will take ruxolitinib for 56 more days, and then stop treatment. If ATL returns, they may restart treatment and continue it for as long as it is effective.