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

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

NCT ID: NCT05592015

Condition: T-Cell Large Granular Lymphocyte Leukemia

Conditions: Official terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Large Granular Lymphocytic
Janus Kinase Inhibitors

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Ruxolitinib
Description: Given PO
Arm group label: Treatment (ruxolitinib)

Other name: INCB-18424

Other name: INCB18424

Other name: Jakafi

Other name: Oral JAK Inhibitor INCB18424

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. Rate of conversion from PR at 4 months to CR at 8 and 12 months (at full ruxolitinib dosage). II. Rate of molecular remission (T-cell receptor [TCR] clearance, STAT3 mutation clearance) at 4, 8, 12 months. III. Incidence of grade III/IV toxicities (at full ruxolitinib dosage). IV. 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. II. Leukemia-free survival III. Progression-free survival 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.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Age 18 or older and able to swallow pills - 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 or failed at least one line of frontline therapy; - Patients must be 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. Platelet transfusion may be utilized to meet inclusion criteria, as long as the platelet count remains >50,000/uL within 5 days of last transfusion. Note: Patients with platelets <100 x 109/L and renal impairment are not permitted to enroll to the study. Renal impairment is defined as creatinine clearance (CrCl) < 90 mL/min. - Serum creatinine =< 2 x the upper limit of normal (ULN) - - Estimated glomerular filtration rate (eGFR) => 30 mL/min using the Modification of Diet in Renal Disease (MDRD) equation (multiplying eGFR by each subjects Body Surface Area [BSA]) - 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) =< 2.5 x ULN - Alkaline phosphatase (ALP) =< 2.5 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 treatment until 5 half-lives have passed. Male subject agrees to use an acceptable method for contraception for the duration of the study treatment until 5 half-lives have passed. - 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 - For females of childbearing potential: Positive pregnancy test or lactating - Unstable angina or myocardial infarction within the past 2 months - Chronic obstructive pulmonary disease or other interstitial lung disease in active exacerbation - Cirrhosis

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Memorial Sloan Kettering Cancer Center

Address:
City: New York
Zip: 10065
Country: United States

Status: Recruiting

Contact:
Last name: Alison Moskowitz, MD

Phone: 646-608-3726
Email: moskowia@mskcc.org

Investigator:
Last name: Alison Moskowitz, MD
Email: Principal Investigator

Facility:
Name: Ohio State University Comprehensive Cancer Center

Address:
City: Columbus
Zip: 43210
Country: United States

Status: Recruiting

Contact:
Last name: Jonathan Brammer, MD

Phone: 614-366-6963
Email: Jonathan.Brammer@osumc.edu

Investigator:
Last name: Jonathan Brammer, MD
Email: Principal Investigator

Start date: May 3, 2023

Completion date: December 31, 2025

Lead sponsor:
Agency: Jonathan Brammer
Agency class: Other

Source: Ohio State University Comprehensive Cancer Center

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05592015
http://cancer.osu.edu