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

NCT05592015 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: OSU-21336NCI-2022-02385
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

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.

Conditions

T-Cell Large Granular Lymphocyte Leukemia

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 12 months

Secondary Outcomes (6)

• Incidence of treatment-emergent adverse events

  Up to 12 months

• Leukemia-free survival (LFS)

  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

• Patient quality-of-life (QOL) EORTC

  Up to 12 months

• Patient quality-of-life (QOL) QLQ-C30

  Up to 12 months

• Patient quality-of-life (QOL) HAQDi

  Up to 12 months

Study Arms (1)

Treatment (ruxolitinib)

EXPERIMENTAL

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.

Drug: Ruxolitinib

Interventions

Ruxolitinib DRUG

Given PO

Also known as: INCB-18424, INCB18424, Jakafi, Oral JAK Inhibitor INCB18424

Treatment (ruxolitinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 or older and able to swallow pills
• Diagnosis of T-LGLL defined as: LGL cell population meeting diagnostic criteria (defined as CD3+CD8+ cell population \>650/mm3 or CD3+CD8+CD57+ population \>500/mm3 or LGL cell population with other immunophenotype that includes co-expression of CD3+, CD8+, CD57+ with \>500 cells/mm3 and the presence of a clonal T-cell receptor (within 1 month of diagnosis or relapse). This also includes patients with rare T-LGLL variants include CD4+ T-LGLL, and gamma/delta T-LGLL which can be CD4- and CD8-), though patients still must have the presence of a clonal T-cell receptor within 1 month of diagnosis or relapse. 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
• 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

You may not qualify if:

• 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. Patients with tuberculosis risk factors will be required to undergo quantiferon testing and/or purified protein derivative (PPD) testing with a negative result prior to entering the study.
• Concurrent immune-suppressive therapy (prednisone or equivalent up to 20 mg permitted to treat LGLL 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
• For any strong CYP3A4 inhibitors deemed a moderate or severe risk of interaction with ruxolitinib, a wash-out period of 14 days, or 5 half-lives, whichever is longer, is needed prior to starting ruxolitinib
• Given the CYP3A4 inhibition potential of grapefruit, grapefruit juice, Seville orange juice, pomelos, and starfruits, patients will need to refrain from these foods/drinks for 14 days prior to initiation of therapy, and throughout the study period

Sponsors & Collaborators

• Jonathan Brammer: lead

Study Sites (3)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Large Granular Lymphocytic

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Leukemia, T-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Jonathan Brammer, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Lily Yang

CONTACT

614-293-6191; lily.yang@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 18, 2022
• First Posted: October 24, 2022
• Study Start: May 3, 2023
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: February 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)