Phase II Trial Evaluating the Safety and Efficacy of Ruxolitinib in Patients With Smoldering and Chronic Adult T-cell Leukemia (ATL)
- 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 smoldering
or chronic adult T-cell leukemia.
- Patients must have measurable or evaluable disease. Patients with > 10% of their PBMCs
having the characteristic abnormal (i.e., CD3 dim, CD4 plusCD25 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.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Clinical Response Rate
after treatment ends (could be 1 or many months)
Kevin C Conlon, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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