Clinical Trials /

Ruxolitinib for Adult T-Cell Leukemia

NCT01712659

Description:

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.

Related Conditions:
  • T-cell Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ruxolitinib for Adult T-Cell Leukemia
  • Official Title: Phase II Trial Evaluating the Safety and Efficacy of Ruxolitinib in Patients With Smoldering and Chronic Adult T-cell Leukemia (ATL)

Clinical Trial IDs

  • ORG STUDY ID: 130006
  • SECONDARY ID: 13-C-0006
  • NCT ID: NCT01712659

Conditions

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

Interventions

DrugSynonymsArms
Ruxolitinib3- Dose Expansion
ruxolitinib3- Dose Expansion

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.

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 maximum tolerated dose and clinical response rate for ruxolitinib given

      at doses of 30, 40 or 50 mg orally twice daily in patients with smoldering, chronic and

      biologically indolent acute or lymphomatous subtype of ATL

      Eligibility

        -  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 months.

        -  Patients must have measurable or evaluable disease. Patients with > 10% of their PBMCs
           having the characteristic abnormal (i.e., CD3dim, 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 another JAK inhibitor; patients previously treated in this
           protocol

      at the lower dose are eligible to restart treatment at the higher dose levels.

      Design

      - This is a pilot open-label, trial of oral ruxolitinib that will enroll 27 to 33 patients
      with

      smoldering or chronic or clinically indolent ATL. Groups of 3 to 6 newly enrolled or

      reenrolled patients will begin treatment at a dose of 30 mg orally given twice daily. If

      this dose is tolerated without exceeding the criteria for dose limiting toxicity (DLT)

      during the first cycle of treatment, the tolerability of treatment at 40 mg and then 50 mg

      twice daily will be evaluated.
    

Trial Arms

NameTypeDescriptionInterventions
1- CLOSEDExperimentalRuxolitinib 20mg orally twice daily for 28 days. Patients may continue to receive treatment until PD
  • Ruxolitinib
  • ruxolitinib
2- Dose EscalationExperimentalRuxolitinib 30-50 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Patients may continue to receive treatment until PD or unacceptable toxicity
  • Ruxolitinib
  • ruxolitinib
3- Dose ExpansionExperimentalRuxolitinib at the MTD orally twice daily for 28 days. Patients may continue to receive treatment until PD or unacceptable toxicity.
  • Ruxolitinib
  • ruxolitinib

Eligibility Criteria

        -  INCLUSION CRITERIA:

        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.

        EXCLUSION CRITERIA:

          -  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, 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 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.

          -  Patients with an absolute requirement for a medication that is a strong inhibitor of
             P450 CYP3A4 are not eligible.
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response rate
Time Frame:After treatment or at time of progressive disease
Safety Issue:
Description:Response rates will be assessed and tabulated

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Trial Keywords

  • JAK 1/2
  • Human T-Cell Lymphotropic Virus 1
  • HTLV-1
  • Janus Kinase Inhibitor

Last Updated

October 19, 2019