Recurrent Diffuse Large B-Cell Lymphoma, Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma, Refractory Diffuse Large B-Cell Lymphoma, Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
Conditions
Brief summary
This phase II trial studies how well ruxolitinib phosphate works in treating patients with diffuse large B-cell or peripheral T-cell non-Hodgkin lymphoma that has returned (relapsed) or that does not respond to treatment (refractory) after donor stem cell transplant. Ruxolitinib phosphate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES: I. Assess the overall response rate (ORR) of subjects with relapsed diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL) who are relapsed or refractory to front-line treatment and ineligible for stem cell transplantation or have recurrent disease after stem cell transplantation to oral ruxolitinib (ruxolitinib phosphate). SECONDARY OBJECTIVES: I. Evaluate safety of oral ruxolitinib in subjects with DLBCL and PTCL. II. Determine progression-free survival (PFS), duration of response, and overall response (OS) in subjects with DLBCL and PTCL. TERTIARY OBJECTIVES: I. Explore the relationship between responses to oral ruxolitinib and alterations in gene expression profiling (GEP) signatures as well as biomarker immunophenotypic changes related to JAK2/STAT3, NF-kB, PI3K/AKT, and mTOR pathways. II. Evaluate potential effect of oral ruxolitinib exposure on JAK2/STAT3 pathway inhibition in serial tumor samples. OUTLINE: Patients receive ruxolitinib phosphate orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months thereafter.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
Given PO
Sponsors
National Cancer Institute (NCI)
University of Nebraska
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must have histologically documented relapsed or refractory disease, with a diagnosis of one of the following lymphoid malignancies: diffuse large B-cell lymphoma, peripheral T-cell lymphoma (any subtype); subjects must have received at least one prior systemic chemotherapy and must have either received an autologous stem cell transplant, refused or been deemed ineligible for an autologous stem cell transplant * Subjects must be willing and able to have a fresh tumor biopsy prior to start of study treatment for research evaluations and cohort categorizing; Note: if insufficient fresh tissue is obtained to provide sub-classification for cohorts, then tissue material from a previous relapse biopsy and/or original diagnostic block may be requested to meet this criterion * Subjects must have measurable lesions (at least one target lesion measuring 2 cm in diameter) by computerized tomography (CT) scan, and/or measurable lymphoma cutaneous lesions of any size * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Absolute neutrophil count (ANC) \>= 1,000/mm\^3 * Platelet count \>= 75,000/mm\^3 * Hemoglobin \>= 8.0 g/dL * Serum creatinine =\< 2.0 g/dL or calculated creatinine clearance \>= 60 mL/min (Cockcroft-Gault method) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x institutional upper limit of normal (ULN) or =\< 5 x ULN if liver involved by lymphoma * Bilirubin \< 2.0 x ULN unless subject has Gilbert's disease, low-grade hemolysis, or liver involvement with lymphoma * At least 2 weeks since prior chemotherapy, biological therapy, radiation therapy, major surgery, other investigational, or anti-cancer therapy that is considered disease-directed and recovered from prior toxicities to grade 0-1 at least 2 weeks prior to investigational therapy * Females will be either postmenopausal for at least 1 year or surgically sterile for at least 3 months; OR females of child-bearing potential must have a negative pregnancy test at screening and agree to take appropriate precautions to avoid pregnancy from screening until 3 months after their last dose of study medication * Males must agree to take appropriate precautions to avoid fathering a child from screening until 3 months after their last dose of study medication * Able to comprehend and willing to sign an informed consent form (ICF)
Exclusion criteria
* History of or active central nervous system (CNS) malignancy * Allogeneic stem cell transplant within the last 6 months, or active-graft-versus-host disease following allogeneic transplant, or subjects currently on immunosuppressive therapy following allogeneic transplant * Uncontrolled intercurrent illness including, but not limited to, ongoing active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements as judged by treating physician; subjects receiving antibiotics that are under control may be included in the study * Pregnant or breastfeeding women * Clinically symptomatic and uncontrolled cardiovascular disease * History of myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure, within the 6 months prior to study drug administration * Current or recent history (\< 21 days prior to start of treatment) of a clinically significant bacterial, viral, fungal, parasitic or mycobacterial infection * History of other malignancy, with the exception of squamous cell carcinoma of the skin, basal cell carcinoma of the skin, cervical intraepithelial neoplasia, or other malignancies that have been in remission for at least 3 years * Presence of a malabsorption syndrome possibly affecting drug absorption (e.g., Crohn's disease or chronic pancreatitis) * Any prior or concomitant use of another JAK inhibitor * Known active hepatitis B or C, or human immunodeficiency virus (HIV) infection * Subjects who, in the opinion of the investigator, are unable or unlikely to comply with the dosing schedule and study evaluations
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | 24 weeks | Number of patients achieving overall response rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From the date of start of treatment to date of death due to any cause, assessed up to 60 months | The Kaplan-Meier method will be used to estimate the median OS time and its 95% CI. |
| Progression-free Survival | From the date of start of treatment to the date of event defined as the first documented progression or death due to any cause, assessed up to 60 months. | The Kaplan-Meier method will be used to estimate the median PFS time and its 95% CI. |
Countries
United States
Participant flow
Recruitment details
Evaluable population - Subjects who had completed 2 cycles of therapy with response assessments or progressed before the evaluation of the primary endpoint. Primary endpoint The primary objective of the study is to evaluate subject overall response rate (ORR) after 6 cycles for each of the subject cohorts. The description provided in this section includes the primary analyses for the primary objective.
Pre-assignment details
For this study 71 subjects were screened and consented for the study. Nine were considered ineligible by the principal investigator and were not treated and removed from the study. Two other subjects were also not included in the data analysis. One withdrew consent prior to treatment. One was determined to have disease progression before treatment started.
Participants by arm
| Arm | Count |
|---|---|
| Diffuse Large B-cell Lymphoma (DLBCL) Patients receive ruxolitinib phosphate PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Correlative studies
Ruxolitinib Phosphate: Given PO | 47 |
| Peripheral T-cell Non-Hodgkin Lymphoma (PTCL) Patients receive ruxolitinib phosphate PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Correlative studies
Ruxolitinib Phosphate: Given PO | 13 |
| Total | 60 |
Baseline characteristics
| Characteristic | Diffuse Large B-cell Lymphoma (DLBCL) | Peripheral T-cell Non-Hodgkin Lymphoma (PTCL) | Total |
|---|---|---|---|
| Age, Continuous | 64 years STANDARD_DEVIATION 11 | 66 years STANDARD_DEVIATION 13 | 65 years STANDARD_DEVIATION 12 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 40 Participants | 12 Participants | 52 Participants |
| Region of Enrollment United States | 47 participants | 13 participants | 60 participants |
| Sex: Female, Male Female | 18 Participants | 5 Participants | 23 Participants |
| Sex: Female, Male Male | 29 Participants | 8 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 31 / 47 | 11 / 13 |
| other Total, other adverse events | 43 / 47 | 12 / 13 |
| serious Total, serious adverse events | 22 / 47 | 7 / 13 |
Outcome results
Primary
Overall Response Rate
Number of patients achieving overall response rate
Time frame: 24 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Diffuse Large B-cell Lymphoma (DLBCL) | Overall Response Rate | Partial Response | 3 Participants |
| Diffuse Large B-cell Lymphoma (DLBCL) | Overall Response Rate | Progressive disease | 34 Participants |
| Diffuse Large B-cell Lymphoma (DLBCL) | Overall Response Rate | Stable disease | 5 Participants |
| Diffuse Large B-cell Lymphoma (DLBCL) | Overall Response Rate | Not assessed | 4 Participants |
| Diffuse Large B-cell Lymphoma (DLBCL) | Overall Response Rate | Complete Response | 1 Participants |
| Peripheral T-cell Non-Hodgkin Lymphoma (PTCL) | Overall Response Rate | Not assessed | 1 Participants |
| Peripheral T-cell Non-Hodgkin Lymphoma (PTCL) | Overall Response Rate | Complete Response | 1 Participants |
| Peripheral T-cell Non-Hodgkin Lymphoma (PTCL) | Overall Response Rate | Partial Response | 1 Participants |
| Peripheral T-cell Non-Hodgkin Lymphoma (PTCL) | Overall Response Rate | Stable disease | 3 Participants |
| Peripheral T-cell Non-Hodgkin Lymphoma (PTCL) | Overall Response Rate | Progressive disease | 7 Participants |
Secondary
Overall Survival (OS)
The Kaplan-Meier method will be used to estimate the median OS time and its 95% CI.
Time frame: From the date of start of treatment to date of death due to any cause, assessed up to 60 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Diffuse Large B-cell Lymphoma (DLBCL) | Overall Survival (OS) | 5.9 Months |
| Peripheral T-cell Non-Hodgkin Lymphoma (PTCL) | Overall Survival (OS) | 6.9 Months |
Secondary
Progression-free Survival
The Kaplan-Meier method will be used to estimate the median PFS time and its 95% CI.
Time frame: From the date of start of treatment to the date of event defined as the first documented progression or death due to any cause, assessed up to 60 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Diffuse Large B-cell Lymphoma (DLBCL) | Progression-free Survival | 1.8 Months |
| Peripheral T-cell Non-Hodgkin Lymphoma (PTCL) | Progression-free Survival | 2.2 Months |