Ruxolitinib for Adult T-Cell Leukemia

This study is currently recruiting participants.
Verified July 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01712659
First received: October 20, 2012
Last updated: March 19, 2014
Last verified: July 2013
  Purpose

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. 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.

Objectives:

- 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.

Condition Intervention Phase
T Cell Leukemia, Adult
Leukemia, Adult T-Cell
T Cell Leukemia, HTLV I Associated
Drug: Ruxolitinib
Phase 2

Study Type: Interventional
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)

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Clinical Response Rate [ Time Frame: after treatment ends (could be 1 or many months) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety profile, time to progression and survival time. [ Time Frame: after 28 days of treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
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)
Intervention Details:
    Drug: Ruxolitinib
    20 mg orally twice daily
Detailed Description:

Background:

  • 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.

Primary Objective:

- 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.

Eligibility

  • 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.

Design

- 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Patients greater than or equal to 18 years old with pathologically confirmed adult T- cell leukemia: smoldering or chronic adult T- cell leukemia as defined by Shimoyama. Patients with 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 may also be considered eligible.
  • 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.

EXCLUSION CRITERIA:

  • Patients previously treated with a JAK inhibitor.
  • 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 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, active or chronic hepatitis B with evidence of end organ damage or dysfunction, hepatitis C or HTLV-II infection.
  • - 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.
  • - A positive hepatitis C serology is an exclusion criterion.
  • 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.
  • Pregnant and breast-feeding patients are not eligible for the study because the effects of ruxolitinib on the developing fetus are unknown.
  • 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 4 months 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01712659

Contacts
Contact: Tatyana Worthy, R.N. (301) 496-6653 worthyt@mail.nih.gov
Contact: Kevin C Conlon, M.D. (301) 402-2913 conlonkc@mail.nih.gov

Locations
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      
Sponsors and Collaborators
Investigators
Principal Investigator: Kevin C Conlon, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01712659     History of Changes
Other Study ID Numbers: 130006, 13-C-0006
Study First Received: October 20, 2012
Last Updated: March 19, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
JAK 1/2
Human T-Cell Lymphotropic Virus 1
HTLV-1
Janus Kinase Inhibitor

Additional relevant MeSH terms:
Leukemia
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Neoplasms by Histologic Type
Neoplasms
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on April 17, 2014