Ruxolitinib for Adult T-Cell Leukemia
- 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. It also affects the growth and reproduction of cells infected with the virus.
- Ruxolitinib is a drug that has been approved to treat bone marrow disorders. It can interfere with the proteins that are important to the development and growth of ATL cells. Drugs like ruxolitinib may be able to interrupt important activity in ATL cells. Researchers want to see if ruxolitinib can be a safe and effective treatment for ATL.
- To test the safety and effectiveness of ruxolitinib for adult T-cell leukemia.
- Individuals at least 18 years of age who have ATL caused by HTLV-1.
- 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.
T Cell Leukemia, Adult
Leukemia, Adult T-Cell
T Cell Leukemia, HTLV I Associated
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial Evaluating the Safety and Efficacy of Ruxolitinib in Patients With Smoldering and Chronic Adult T-cell Leukemia (ATL)|
- Clinical Response Rate [ Time Frame: after treatment ends (could be 1 or many months) ] [ Designated as safety issue: No ]
- Safety profile, time to progression and survival time. [ Time Frame: after 28 days of treatment ] [ Designated as safety issue: No ]
|Study Start Date:||October 2012|
|Estimated Study Completion Date:||September 2015|
|Estimated Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
- Adult T-cell leukemia is a lymphoproliferative disorder characterized by the presence of CD4/CD25 expressing T cells (IL-2R alpha expressing) in the peripheral blood, in lymphoid and other tissues.
- In smoldering and chronic ATL the HTLV-1 encoded protein, Tax constitutively activates interleukin-2 (IL-2), IL-9 and IL-15 autocrine/paracrine systems that in turn activate the Janus kinase (JAK)-1/3/STAT5 pathways.
- Ruxolitinib a therapeutic agent inhibits cytokine mediated JAK1/2 activation and ex vivo proliferation of malignant T cells from patients with ATL.
- Ruxolitinib is a potent orally bioavailable JAK1/2 inhibitor.
- To determine the clinical response rate of patients with smoldering or chronic ATL to ruxolitinib when administered at a dose of 20 mg orally twice a day for 28 days.
- Patients greater than or equal to 18 years old with pathologically confirmed adult T-cell leukemia: smoldering or or previously treated lymphomatous or acute subtypes with clinically indolent behavior indicated by lack of significant symptoms and treatment free interval of greater than 6 months.
- Patients must have measurable or evaluable disease. Patients with > 10% of their PBMCs having the characteristic abnormal (i.e., CD3 (dim), CD4 plus CD25 plus expressing) FACS profile for circulating ATL cells will be considered to have measurable disease.
- Patients with symptomatic leukemic meningitis, bony or GI tract involvement, serum calcium or LDH > 1.5 times the upper limit of normal will be excluded. However patients that have both ATL and another HTLV-1 associated disease such as tropical spastic paraparesis (HAM/TSP) will be included.
- No prior treatment with a JAK inhibitor.
- This is a phase II open-label, trial of oral ruxolitinib that will enroll 20 patients with smoldering or chronic ATL. The patients will be treated with the standard dosage and schedule (20 mg orally twice daily) approved by the FDA for the treatment of Myelofibrosis.
|Contact: Tatyana Worthy, R.N.||(301) firstname.lastname@example.org|
|Contact: Kevin C Conlon, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Kevin C Conlon, M.D.||National Cancer Institute (NCI)|