Ruxolitinib for the Treatment of T-Cell Large Granular Lymphocytic Leukemia
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorJonathan Brammer
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
Absolute neutrophil count (ANC) less than 100/mm^3. Note: granulocyte colony-stimulating factor (G-CSF) may be utilized to enable patients to meet inclusion criteria, as long as the ANC remains above 100/mm^3 for 5 days after administration of last growth-factor.
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
Trial design
Design model
Single group
Treatments tested in this trial
Ruxolitinib
DrugGiven PO
Treatment groups
30 Participants
are divided into 1 treatment groupGroup A: Treatment (ruxolitinib)Experimental treatment 1 intervention
Trial outcomes
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.
Time frame
Up to 12 monthsSecondary outcomes
1
Incidence of treatment-emergent adverse events
Treatment-emergent adverse events will be reported overall and by toxicity grade.
Time frame
Up to 12 months2
Leukemia-free survival (LFS)
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 months3
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.
Time frame
Up to 12 months4
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.
Time frame
Up to 12 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Jonathan Brammer
Lead sponsor
Ohio State University Comprehensive Cancer Center
Sponsor institution
Source ClinicalTrials.gov