Know Cancer

or
forgot password

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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
T Cell Leukemia, Adult, Leukemia, Adult T-Cell, T Cell Leukemia, HTLV I Associated

Thank you

Trial Information

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


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 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.

Inclusion Criteria


- INCLUSION CRITERIA:

- Patients greater than or equal to 18 years old with pathologically confirmed
smoldering or chronic adult T- cell leukemia as defined by Shimoyama.

- 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 1000 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 HIV, active bacterial infections, active or chronic hepatitis B, 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.

- A positive hepatitis C serology is an exclusion criterion.

- 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.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Clinical Response Rate

Outcome Time Frame:

after treatment ends (could be 1 or many months)

Safety Issue:

No

Principal Investigator

Kevin C Conlon, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Federal Government

Study ID:

130006

NCT ID:

NCT01712659

Start Date:

October 2012

Completion Date:

September 2015

Related Keywords:

  • T Cell Leukemia, Adult
  • Leukemia, Adult T-Cell
  • T Cell Leukemia, HTLV I Associated
  • JAK 1/2
  • Human T-Cell Lymphotropic Virus 1
  • HTLV-1
  • Janus Kinase Inhibitor
  • Leukemia
  • Leukemia, T-Cell
  • Leukemia-Lymphoma, Adult T-Cell

Name

Location

National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892