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Ruxolitinib for the Treatment of T-Cell Large Granular Lymphocytic Leukemia

Primary Purpose

T-Cell Large Granular Lymphocyte Leukemia

Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ruxolitinib
Sponsored by
Ohio State University Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for T-Cell Large Granular Lymphocyte Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age 18 or older
  • Diagnosis of T-LGLL defined as: CD3+CD8+ cell population > 650/mm^3 or CD3+CD8+CD57+ population > 500/mm^3 and the presence of a clonal T-cell receptor (within 1 month of diagnosis). Note: patients with MDS-like T-LGLL may be included with PI approval even if CD3+CD8+ cell population is < 650/mm^3, though +TCR is required. Natural-Killer (NK) LGL is also permitted, provided there is a clonal NK-cell population noted with > 500 cells/mm^3
  • Untreated T-LGLL
  • Failed at least one line of frontline therapy; off treatment for at least 14 days or 5 half-lives, whichever is longer

  • Require Treatment for T-LGLL (one or more required)

    • Symptomatic anemia with hemoglobin < 10 g/dL
    • Transfusion-dependent anemia
    • Neutropenia with absolute neutrophil count (ANC) < 500/mm^3
    • Neutropenia with ANC < 1500/mm^3 with recurrent infections
  • Platelet count > 50 x 10^9/L
  • Serum creatinine =< 2 x the upper limit of normal (ULN)
  • Total bilirubin =< 1.5 x ULN (patients with Gilbert's syndrome with a bilirubin > 1.5 x ULN permitted)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 1.5 x ULN
  • Eastern cooperative oncology group (ECOG) performance status =< 2
  • Men and women of reproductive potential must agree to follow accepted birth control methods for the duration of the study. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study
  • Able to sign informed consent

Exclusion Criteria:

  • Absolute neutrophil count (ANC) less than 100/mm^3
  • Active infection requiring ongoing anti-microbial treatment. Patients with human immunodeficiency virus (HIV), positive hepatitis B surface antigen or hepatitis C antibody will be excluded
  • Concurrent immune-suppressive therapy (prednisone or equivalent up to 20 mg permitted to treat T-LGL symptoms, but must be weaned within one month of initiation of trial drug). Patients on stable, chronic prednisone =< 10 mg for rheumatologic/autoimmune conditions are exempted from this requirement. They may enroll on the study
  • Active, concurrent malignancy unless deemed related to T-LGLL by principal investigator (PI). Early stage skin cancers, prostate cancer, permitted if under no active therapy
  • Positive pregnancy test
  • Platelet count < 50,000/uL
  • Unstable angina or myocardial infarction within the past 2 months
  • Chronic obstructive pulmonary disease or other interstitial lung disease in active exacerbation
  • Serum alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin, or alkaline phosphatase > 1.5 x upper limit of normal (ULN) (unless document Gilbert's)
  • Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m^2 using the Modification of Diet in Renal Disease (MDRD) equation

Sites / Locations

  • Ohio State University Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (ruxolitinib)

Arm Description

Patients receive ruxolitinib PO BID on days 1-28. Cycles repeat every 28 days for 12 months in the absence of disease progression or unacceptable toxicity. Patients who achieve a response (CR or PR) may receive an additional 12 months of ruxolitinib, for a maximum of 24 months.

Outcomes

Primary Outcome Measures

Overall response rate (ORR)
The ORR will be calculated as the proportion of patients who achieve a response to therapy divided by the total number of evaluable patients. An evaluable patient is defined as an eligible patient who has received at least four months of therapy with ruxolitinib. All evaluable patients will be included in calculating the ORR for the study along with corresponding 95% binomial confidence intervals (CIs) (assuming that the number of patients who respond is binomially distributed). Additional outcomes including rates of conversion from PR at 4 months to CR at 8 and 12 months on full dose ruxolitinib, and rate of molecular remission (TCR clearance, STAT3 mutation clearance) at 4, 8, 12 months on full dose ruxolitinib will also be reported as proportions with 95% binomial CIs.

Secondary Outcome Measures

Incidence of treatment-emergent adverse events
Treatment-emergent adverse events will be reported overall and by toxicity grade.
Leukemia-free survival (LFS)
Kaplan Meier curves will be generated and the median LFS and 95% CIs will be reported.
Patient quality-of-life (QOL) EORTC
Will be assessed via responses to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire at baseline, 5 months, and 1 year on study. Changes in QOL will be calculated from the differences in scores between baseline and 5 months, baseline and 1 year, and 5 months and 1 year, for each patient. The proportions of patients who had improvement in QOL scores between time points will be compared between responding patients and non-responding patients, patients with and without rheumatologic disease, and between patients classified as having an objective benefit and patients who did not have an objective benefit. Mean changes in patient QOL between time points will also be reported.
Patient quality-of-life (QOL) QLQ-C30
Will be assessed via responses to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 given at baseline, 5 months, and 1 year on study. Changes in QOL will be calculated from the differences in scores between baseline and 5 months, baseline and 1 year, and 5 months and 1 year, for each patient. The proportions of patients who had improvement in QOL scores between time points will be compared between responding patients and non-responding patients, patients with and without rheumatologic disease, and between patients classified as having an objective benefit and patients who did not have an objective benefit. Mean changes in patient QOL between time points will also be reported.
Patient quality-of-life (QOL) HAQDi
Will be assessed via responses to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Health Assessment Questionnaire-Disability Index questionnaires given at baseline, 5 months, and 1 year on study. Changes in QOL will be calculated from the differences in scores between baseline and 5 months, baseline and 1 year, and 5 months and 1 year, for each patient. The proportions of patients who had improvement in QOL scores between time points will be compared between responding patients and non-responding patients, patients with and without rheumatologic disease, and between patients classified as having an objective benefit and patients who did not have an objective benefit. Mean changes in patient QOL between time points will also be reported.
Patient quality-of-life (QOL) SF-36
Will be assessed via responses to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Short Form-36 given at baseline, 5 months, and 1 year on study. Changes in QOL will be calculated from the differences in scores between baseline and 5 months, baseline and 1 year, and 5 months and 1 year, for each patient. The proportions of patients who had improvement in QOL scores between time points will be compared between responding patients and non-responding patients, patients with and without rheumatologic disease, and between patients classified as having an objective benefit and patients who did not have an objective benefit. Mean changes in patient QOL between time points will also be reported.

Full Information

First Posted
April 18, 2022
Last Updated
October 20, 2022
Sponsor
Ohio State University Comprehensive Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT05592015
Brief Title
Ruxolitinib for the Treatment of T-Cell Large Granular Lymphocytic Leukemia
Official Title
A Phase II Study Evaluating the Efficacy of Ruxolitinib in Patients With T-Cell Large Granular Lymphocytic Leukemia (T-LGLL)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 1, 2022 (Anticipated)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ohio State University Comprehensive Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial tests whether ruxolitinib works to shrink tumors in patients with T-cell large granular lymphocyte leukemia. Ruxolitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Detailed Description
PRIMARY OBJECTIVE: I. Determine the overall response rate (ORR) of ruxolitinib in patients with T-cell large granular lymphocytic leukemia (T-LGLL) as compared to historical controls. SECONDARY OBJECTIVES: I. To determine the overall response rate (complete response [CR] and partial response [PR]) of ruxolitinib in patients with T-LGLL. II. Duration of response to ruxolitinib. III. Leukemia-free survival. IV. Rate of conversion from PR at 4 months to CR at 8 and 12 months (at full ruxolitinib dosage). V. Rate of molecular remission (T-cell receptor [TCR] clearance, STAT3 mutation clearance) at 4, 8, 12 months. VI. Incidence of grade III/IV toxicities (at full ruxolitinib dosage). VII. Quality of life using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Core 30 (C30), Health Assessment Questionnaire-Disability Index (HAQDi), Short Form (SF)-36 questionnaire at baseline, after 5 months, 1 year of treatment. EXPLORATORY OBJECTIVE: I. Objective benefit (OB) rate at 4 months defined as a patient that had improvement in their cytopenias, transfusion dependence but not attaining a PR. OUTLINE: Patients receive ruxolitinib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days for 12 months in the absence of disease progression or unacceptable toxicity. Patients who achieve a response (CR or PR) may receive an additional 12 months of ruxolitinib, for a maximum of 24 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
T-Cell Large Granular Lymphocyte Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (ruxolitinib)
Arm Type
Experimental
Arm Description
Patients receive ruxolitinib PO BID on days 1-28. Cycles repeat every 28 days for 12 months in the absence of disease progression or unacceptable toxicity. Patients who achieve a response (CR or PR) may receive an additional 12 months of ruxolitinib, for a maximum of 24 months.
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Other Intervention Name(s)
INCB-18424, INCB18424, Jakafi, Oral JAK Inhibitor INCB18424
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
The ORR will be calculated as the proportion of patients who achieve a response to therapy divided by the total number of evaluable patients. An evaluable patient is defined as an eligible patient who has received at least four months of therapy with ruxolitinib. All evaluable patients will be included in calculating the ORR for the study along with corresponding 95% binomial confidence intervals (CIs) (assuming that the number of patients who respond is binomially distributed). Additional outcomes including rates of conversion from PR at 4 months to CR at 8 and 12 months on full dose ruxolitinib, and rate of molecular remission (TCR clearance, STAT3 mutation clearance) at 4, 8, 12 months on full dose ruxolitinib will also be reported as proportions with 95% binomial CIs.
Time Frame
Up to 12 months
Secondary Outcome Measure Information:
Title
Incidence of treatment-emergent adverse events
Description
Treatment-emergent adverse events will be reported overall and by toxicity grade.
Time Frame
Up to 12 months
Title
Leukemia-free survival (LFS)
Description
Kaplan Meier curves will be generated and the median LFS and 95% CIs will be reported.
Time Frame
From first response until disease progression, death, or censoring (if alive and disease-free at the end of follow-up), assessed up to 12 months
Title
Patient quality-of-life (QOL) EORTC
Description
Will be assessed via responses to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire at baseline, 5 months, and 1 year on study. Changes in QOL will be calculated from the differences in scores between baseline and 5 months, baseline and 1 year, and 5 months and 1 year, for each patient. The proportions of patients who had improvement in QOL scores between time points will be compared between responding patients and non-responding patients, patients with and without rheumatologic disease, and between patients classified as having an objective benefit and patients who did not have an objective benefit. Mean changes in patient QOL between time points will also be reported.
Time Frame
Up to 12 months
Title
Patient quality-of-life (QOL) QLQ-C30
Description
Will be assessed via responses to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 given at baseline, 5 months, and 1 year on study. Changes in QOL will be calculated from the differences in scores between baseline and 5 months, baseline and 1 year, and 5 months and 1 year, for each patient. The proportions of patients who had improvement in QOL scores between time points will be compared between responding patients and non-responding patients, patients with and without rheumatologic disease, and between patients classified as having an objective benefit and patients who did not have an objective benefit. Mean changes in patient QOL between time points will also be reported.
Time Frame
Up to 12 months
Title
Patient quality-of-life (QOL) HAQDi
Description
Will be assessed via responses to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Health Assessment Questionnaire-Disability Index questionnaires given at baseline, 5 months, and 1 year on study. Changes in QOL will be calculated from the differences in scores between baseline and 5 months, baseline and 1 year, and 5 months and 1 year, for each patient. The proportions of patients who had improvement in QOL scores between time points will be compared between responding patients and non-responding patients, patients with and without rheumatologic disease, and between patients classified as having an objective benefit and patients who did not have an objective benefit. Mean changes in patient QOL between time points will also be reported.
Time Frame
Up to 12 months
Title
Patient quality-of-life (QOL) SF-36
Description
Will be assessed via responses to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Short Form-36 given at baseline, 5 months, and 1 year on study. Changes in QOL will be calculated from the differences in scores between baseline and 5 months, baseline and 1 year, and 5 months and 1 year, for each patient. The proportions of patients who had improvement in QOL scores between time points will be compared between responding patients and non-responding patients, patients with and without rheumatologic disease, and between patients classified as having an objective benefit and patients who did not have an objective benefit. Mean changes in patient QOL between time points will also be reported.
Time Frame
Up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18 or older Diagnosis of T-LGLL defined as: CD3+CD8+ cell population > 650/mm^3 or CD3+CD8+CD57+ population > 500/mm^3 and the presence of a clonal T-cell receptor (within 1 month of diagnosis). Note: patients with MDS-like T-LGLL may be included with PI approval even if CD3+CD8+ cell population is < 650/mm^3, though +TCR is required. Natural-Killer (NK) LGL is also permitted, provided there is a clonal NK-cell population noted with > 500 cells/mm^3 Untreated T-LGLL Failed at least one line of frontline therapy; off treatment for at least 14 days or 5 half-lives, whichever is longer Require Treatment for T-LGLL (one or more required) Symptomatic anemia with hemoglobin < 10 g/dL Transfusion-dependent anemia Neutropenia with absolute neutrophil count (ANC) < 500/mm^3 Neutropenia with ANC < 1500/mm^3 with recurrent infections Platelet count > 50 x 10^9/L Serum creatinine =< 2 x the upper limit of normal (ULN) Total bilirubin =< 1.5 x ULN (patients with Gilbert's syndrome with a bilirubin > 1.5 x ULN permitted) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 1.5 x ULN Eastern cooperative oncology group (ECOG) performance status =< 2 Men and women of reproductive potential must agree to follow accepted birth control methods for the duration of the study. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study Able to sign informed consent Exclusion Criteria: Absolute neutrophil count (ANC) less than 100/mm^3 Active infection requiring ongoing anti-microbial treatment. Patients with human immunodeficiency virus (HIV), positive hepatitis B surface antigen or hepatitis C antibody will be excluded Concurrent immune-suppressive therapy (prednisone or equivalent up to 20 mg permitted to treat T-LGL symptoms, but must be weaned within one month of initiation of trial drug). Patients on stable, chronic prednisone =< 10 mg for rheumatologic/autoimmune conditions are exempted from this requirement. They may enroll on the study Active, concurrent malignancy unless deemed related to T-LGLL by principal investigator (PI). Early stage skin cancers, prostate cancer, permitted if under no active therapy Positive pregnancy test Platelet count < 50,000/uL Unstable angina or myocardial infarction within the past 2 months Chronic obstructive pulmonary disease or other interstitial lung disease in active exacerbation Serum alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin, or alkaline phosphatase > 1.5 x upper limit of normal (ULN) (unless document Gilbert's) Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m^2 using the Modification of Diet in Renal Disease (MDRD) equation
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
The Ohio State University Comprehensive Cancer Center
Phone
800-293-5066
Email
OSUCCCClinicaltrials@osumc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jonathan E Brammer, MD
Organizational Affiliation
Ohio State University Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jonathan E. Brammer
Phone
614-293-9563
Email
jonathan.brammer@osumc.edu
First Name & Middle Initial & Last Name & Degree
Jonathan E. Brammer

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://cancer.osu.edu
Description
The Jamesline

Learn more about this trial

Ruxolitinib for the Treatment of T-Cell Large Granular Lymphocytic Leukemia

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