Ruxolitinib in Treating Patients with Relapsed or Refractory T-cell or NK Cell Lymphoma
This phase II trial studies ruxolitinib in treating patients with T-cell or natural killer (NK) cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Ruxolitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Inclusion Criteria
- Pathologically confirmed T or NK cell lymphoma at the enrolling institution; for cutaneous T-cell non-Hodgkin lymphoma (CTCL), patients with stage IB disease or greater are eligible
- Relapse or refractory disease after at least 1 systemic therapy except for T-cell-prolymphocytic leukemia (T-PLL), large granular lymphocyte (LGL), or T-cell Lymphoproliferative diseases with JAK2 fusion untreated patients may be allowed after discussion with principal investigator (P.I.)
- Age >= 18
- Eastern Cooperative Oncology Group (ECOG) =< 2
- Measurable disease defined by: * Lugano classification for systemic lymphoma or * Atypical and or malignant lymphocytes quantifiable by flow cytometry or morphology in blood or bone marrow or * Modified severity-weighted assessment tool (mSWAT) > 0 or Sezary count >= 1000 cells/uL for CTCL
- Previous systemic anti-cancer therapy for T-cell lymphoma must have been discontinued at least 2 weeks prior to treatment; * Glucocorticoids aimed at controlling lymphoma-related symptoms are allowed as long as they are tapered down to 20 mg or less by the time of ruxolitinib initiation * Topical steroids for CTCL are permitted
- Absolute neutrophil count (ANC) >= 1.0/mm^3 or ANC >= 0.5/mm^3 (if patient has baseline neutropenia due to lymphoma)
- Platelets >= 100 x 10^9/L or >= 50 x 10^9/L (if related to lymphoma)
- Hemoglobin (Hgb) >= 8 g/dL
- Patients with LGL or T-PLL are not required to meet a minimum ANC or hemoglobin value for eligibility
- Total bilirubin =< 1.5 x upper limit of normal (ULN) or =< 3 x ULN if documented hepatic involvement with lymphoma, or =< 5 x ULN if history of Gilbert's syndrome
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN; =< 5 if due to lymphoma involvement * Patients with elevated bilirubin for reasons other than liver dysfunction (e.g. hemolysis) are eligible after discussion with Memorial Sloan Kettering (MSK) principal investigator (PI)
- Creatinine clearance >= 30 mL/min; creatinine clearance of 15-29 mL/min will be allowed as long as baseline platelets are >= 150 x 10^9/L
- For patients with positive hepatitis B core antibody or surface antigen, hepatitis B polymerase chain reaction (PCR) must be negative and prophylaxis with entecavir or equivalent is required
- Patients with human immunodeficiency virus (HIV) are allowed provided that they are on anti-retroviral treatment with no active infections
Exclusion Criteria
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
- Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, uncontrolled diabetes, clinically significant pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Eastern Cooperative Oncology Group (ECOG) performance status > 2
- Prior therapy with ruxolitinib
- Receiving systemic therapy for another primary malignancy (other than T-cell lymphoma) * Patients with more than one type of lymphoma may be enrolled after discussion with the Memorial Sloan-Kettering (MSK) principal investigator * Adjuvant or maintenance therapy to reduce the risk of recurrence of other malignancy (other than T-cell lymphoma) is permissible after discussion with the MSK principal investigator
- Women of reproductive potential* must have a negative serum beta human chorionic gonadotropin (beta-HCG) pregnancy test * A female of reproductive potential is a sexually mature female who: has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months (i.e. has had menses at any time during the preceding 24 consecutive months)
Additional locations may be listed on ClinicalTrials.gov for NCT02974647.
Locations matching your search criteria
United States
New Jersey
Basking Ridge
Middletown
Montvale
New York
Commack
New York
Uniondale
West Harrison
PRIMARY OBJECTIVE:
I. Estimate the disease control rate (complete response, partial response, and stable disease rates) to ruxolitinib in mature T-cell and NK-cell non-Hodgkin lymphoma (PTCL) in patients with genetic evidence of JAK/STAT activation, functional evidence of JAK/STAT activation, and patients without genetic or functional evidence of JAK/STAT activation.
SECONDARY OBJECTIVES:
I. Evaluate toxicity associated with ruxolitinib in PTCL.
II. Compare progression free survival among all cohorts.
III. Evaluate for markers of sensitivity and characterize the effects of JAK inhibition in PTCL through the following:
IIIa. Targeted sequencing, whole exome sequencing (WGS), and whole exome sequencing (WES) of select baseline and on-treatment tumors for patients enrolled onto the study to allow for an unbiased assessment for mutations that predict for response to JAK inhibition.
IIIb. Ribonucleic acid sequencing (RNAseq) at baseline, after 1 week of treatment, and at progression will be performed on tumor biopsies or blood (for patients with blood involvement of disease) to evaluate for changes in expression profiling following JAK inhibition.
IIIc. Immunohistochemical staining of baseline tumor samples and on-treatment biopsies for STAT3, phosphorylated (phospho)-STAT3, STAT5, phospho-STAT5, TBX21, and GATA3 to evaluate for biopsy characteristics predictive of response to JAK inhibition.
IIId. Serum cytokines known to be altered by JAK/STAT activation, such as serum interleukin (IL)-10, IL-17, IL-23, IL-6, and interferon (IFN)-gamma, will be measured by multiplex enzyme-linked immunosorbent assay (ELISA) array on day 1 of cycle 1, day 8 of cycle 1, and day 1 of cycle 2 to evaluate down-stream effects of JAK inhibition and identify markers of response.
IIIe. Patient-derived tumor grafts developed from baseline biopsies from patients enrolled on study will be used to further interrogate effects of JAK inhibition in PTCL, identify markers of resistance, and test optimal candidates for combination with JAK inhibition.
IIIf. Single-cell RNA sequencing and additional unbiased proteomics analyses will be performed on baseline and on-treatment samples to understand mechanisms of by which ruxolitinib improved hematologic parameters and to evaluate for changes in protein expression patterns.
IV. Estimate disease control rate for T-Cell/NK Lymphoma patients with JAK2 fusion mutations.
OUTLINE:
Patients receive ruxolitinib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) and positron emission tomography (PET) scan at screening, at the end of cycle 2, 5, and every three cycles thereafter, collection of blood samples on days 1 of cycle 3 and subsequent odd cycles, and at the end of study, and collection of archived tissue at screening. Patients without archived tissue, undergo biopsy at screening, on day 8 and 28 of cycle 1, and at progression.
After completion of study treatment, patients are followed up for 30 days.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorAlison J. Moskowitz
- Primary ID16-1542
- Secondary IDsNCI-2016-01850
- ClinicalTrials.gov IDNCT02974647