Clinical trial NCT05592015: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: T-Cell Large Granular Lymphocyte Leukemia
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2022-10-24
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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. 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.

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

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: Up to 12 months
Secondary outcomes:
measure: Incidence of treatment-emergent adverse events
timeFrame: Up to 12 months
measure: Leukemia-free survival (LFS)
timeFrame: 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
measure: Patient quality-of-life (QOL) EORTC
timeFrame: Up to 12 months
measure: Patient quality-of-life (QOL) QLQ-C30
timeFrame: Up to 12 months
measure: Patient quality-of-life (QOL) HAQDi
timeFrame: Up to 12 months
measure: Patient quality-of-life (QOL) SF-36
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center
name: Jonathan Brammer, MD
role: PRINCIPAL_INVESTIGATOR
References: