- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01431209
Ruxolitinib Phosphate to Treat Diffuse Large B-Cell or Peripheral T-Cell Non-Hodgkin Lymphoma After Stem Cell Transplant
A Phase 2 Multicenter, Investigator Initiated Study of Oral Ruxolitinib Phosphate for the Treatment of Relapsed or Refractory Diffuse Large B-Cell and Peripheral T-Cell Non-Hodgkin Lymphoma
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Maryland
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Bethesda, Maryland, United States, 20892
- National Institutes of Health Clinical Center
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic
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Nebraska
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Omaha, Nebraska, United States, 68198
- University of Nebraska Medical Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (ruxolitinib phosphate)
Patients receive ruxolitinib phosphate PO BID on days 1-28.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
Correlative studies
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate
Time Frame: 24 weeks
|
Number of patients achieving overall response rate
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24 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival (OS)
Time Frame: 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.
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From the date of start of treatment to date of death due to any cause, assessed up to 60 months
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Progression-free Survival
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.
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The Kaplan-Meier method will be used to estimate the median PFS time and its 95% CI.
|
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.
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Julie M Vose, MD, MBA, University of Nebraska
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 0283-11-FB
- NCI-2011-02733 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- P30CA036727 (U.S. NIH Grant/Contract)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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