NIH Clinical Center Search the Studies: Study Number, Study Title

Protocol Details

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

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 18 Years
Max Age: N/A

Referral Letter Required


Population Exclusion(s)

Pregnant Women;


Human T-Cell Lymphotropic Virus 1;
Janus Kinase Inhibitor

Recruitment Keyword(s)



T Cell Leukemia, Adult;
Leukemia, Adult T-Cell;
T Cell Leukemia, HTLV I Associated

Investigational Drug(s)


Investigational Device(s)



Drug: Ruxolitinib 20 mg
Drug: Ruxolitinib 30 mg
Drug: Ruxolitinib 40 mg
Drug: Ruxolitinib 50 mg

Supporting Site

National Cancer Institute


-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


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.


- 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.

--Back to Top--



NOTE: After approval and activation of Amendment D, patients who have failed this protocol treatment previously at the initial dose level may be eligible for re-enrollment and retreatment if they otherwise meet eligibility criteria.

-Patients greater than or equal to 18 years old with pathologically confirmed adult T- cell leukemia: smoldering or chronic, 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 monthsare eligible for treatment in the dose escalation and expansion cohorts.

-Patients must have serum antibodies directed to HTLV-1.

-Patients must have measurable or evaluable disease. Patients with > 10% of the PBMCs having the characteristic abnormal (i.e., CD3dim, CD4 plus CD25 plus expressing) FACS profile for circulating ATL cells will be considered to have evaluable disease.

-Patients must have adequate physiologic parameters:

-Absolute granulocyte count greater than or equal to 500 K/microL, platelet count greater than or equal to 75,000 K/microL and hemoglobin greater than or equal to 10 g/dL.

-Bilirubin and creatinine less than or equal to 1.5 times institutional ULN.

- AST, ALT less than or equal to 3.0 times institutional ULN.

-Karnofsky Performance Score greater than or equal to 70% or ECOG less than or equal 1.

- Patients must be able to understand and sign Informed Consent Form.


-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.

-Patients with symptomatic leukemic meningitis, bony or GI tract involvement, serum calcium or LDH > 1.5 X 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.

-Patients who have received high doses of systemic corticosteroids for the treatment of their ATL within 4 weeks prior to the start of therapy.

-Patients who have received any cytotoxic therapy, immunotherapy, antitumor vaccines or monoclonal antibodies in the 4 weeks prior to the start of the study.

-Life expectancy of less than 3 months.

-Documented active bacterial infections, HTLV-II infection, or hepatitis B or C as follows:

--A positive hepatitis B serology indicative of previous immunization (i.e., HBsAb positive and HBc Ab negative), or a fully resolved acute hepatitis B infection is not an exclusion criterion.

--Patients with an indolent chronic hepatitis B infection (normal ALT, AST, albumin and no radiographic or biopsy evidence of cirrhosis) may be eligible.

--Patients with active hepatitis C are excluded. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.

-Patients who have untreated human immunodeficiency virus (HIV) are not eligible for this study because by definition they have a defective immune response and are at much higher risk for opportunistic infections due to immune disregulation by both HTLV-1 and HTLVIII (HIV) viruses. Patients on HIV therapy with undetectable viral loads as measured by HIV RNA quantitative real time PCR may be eligible.

-Inability or refusal to practice effective contraception during therapy. Men and women of childbearing potential must use an effective method of birth control or abstinence during treatment and for 1 week after completion of the treatment.

-Patient has significant and/or uncontrolled cardiac, renal, hepatic or other systemic disorders or significant psychological conditions at baseline visit that in the investigator s judgment would jeopardize subject enrollment or compliance with the study procedures.

-Patients with an absolute requirement for a medication that is a strong inhibitor of P450 CYP3A4 are not eligible.

--Back to Top--


Matsuoka M, Jeang KT. Human T-cell leukemia virus type 1 (HTLV-1) and leukemic transformation: viral infectivity, Tax, HBZ and therapy. Oncogene. 2011 Mar 24;30(12):1379-89. Epub 2010 Nov 29.

Tsukasaki K, Hermine O, Bazarbachi A, Ratner L, Ramos JC, Harrington W Jr, O'Mahony D, Janik JE, Bittencourt AL, Taylor GP, Yamaguchi K, Utsunomiya A, Tobinai K, Watanabe T. Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma: a proposal from an international consensus meeting. J Clin Oncol. 2009 Jan 20;27(3):453-9. Epub 2008 Dec 8.

Yamada Y, Atogami S, Hasegawa H, Kamihira S, Soda M, Satake M, Yamaguchi K. Nationwide survey of adult T-cell leukemia/lymphoma (ATL) in Japan. Rinsho Ketsueki. 2011 Nov;52(11):1765-71.

--Back to Top--


Principal Investigator

Referral Contact

For more information:

Kevin C. Conlon, M.D.
National Cancer Institute (NCI)
(240) 760-6087

NCI Medical Oncology Referral Office
National Cancer Institute (NCI)

(240) 760-6050

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office

Clinical Trials Number:


--Back to Top--