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Ruxolitinib Phosphate in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell or Peripheral T-Cell Non-Hodgkin Lymphoma After Donor Stem Cell Transplant

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 by Julie M Vose, MD, University of Nebraska
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Julie M Vose, MD, University of Nebraska
ClinicalTrials.gov Identifier:
NCT01431209
First received: September 5, 2011
Last updated: May 1, 2017
Last verified: May 2017
  Purpose
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.

Condition Intervention Phase
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 Other: Laboratory Biomarker Analysis Drug: Ruxolitinib Phosphate Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Julie M Vose, MD, University of Nebraska:

Primary Outcome Measures:
  • Number of patients achieving overall response rate [ Time Frame: 24 weeks ]

Secondary Outcome Measures:
  • Duration of response [ Time Frame: From the date of complete or partial remission documented to date of recurrence/progression, death due to any cause, or lost to follow-up, assessed up to 5 years ]
    The Kaplan-Meier method will be used to estimate the median duration of response and its 95% confidence interval (CI).

  • Incidence of treatment-emergent adverse events (new or worsening from baseline) [ Time Frame: Up to 30 days after study treatment has ended ]
    Summarized by severity and type according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

  • Overall survival (OS) [ Time Frame: From the date of start of treatment to date of death due to any cause, assessed up to 5 years ]
    The Kaplan-Meier method will be used to estimate the median OS time and its 95% CI.

  • 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 5 years ]
    The Kaplan-Meier method will be used to estimate PFS and its 95% CI.


Other Outcome Measures:
  • Alterations in GEP signatures as well as biomarker immunophenotypic changes related to JAK2/STAT3, NF-κB, BCR, PI3K/AKT, and mTOR pathways [ Time Frame: Up to 6 weeks post treatment ]
    Descriptive statistics will be used. Mean, standard deviation, median and range will be reported for markers pre- and post-treatment as well as for the marker changes between pre- and post-treatment. Paired t-test will be used to evaluate the marker changes between pre- and post-treatment. Spearman or Pearson correlation coefficients will be calculated to evaluate the correlations among markers. Logistic regression will be utilized to assess the effects of markers at baseline on response to therapy.


Estimated Enrollment: 90
Study Start Date: August 2011
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Ruxolitinib Phosphate
Given PO
Other Names:
  • INCB-18424 Phosphate
  • Jakafi

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01431209

Locations
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: Wyndham H. Wilson    301-435-2415    wilsonw@mail.nih.gov   
Principal Investigator: Wyndham H. Wilson         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Thomas E. Witzig    507-266-2040    witzig.thomas@mayo.edu   
Principal Investigator: Thomas E. Witzig         
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Contact: Julie M. Vose    402-559-3848    jmvose@unmc.edu   
Principal Investigator: Julie M. Vose         
Sponsors and Collaborators
University of Nebraska
National Cancer Institute (NCI)
Investigators
Principal Investigator: Julie Vose University of Nebraska
  More Information

Responsible Party: Julie M Vose, MD, Principal Investigator, University of Nebraska
ClinicalTrials.gov Identifier: NCT01431209     History of Changes
Other Study ID Numbers: 283-11
NCI-2011-02733 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
12-C-0196
12C0196
283-11 ( Other Identifier: University of Nebraska Medical Center )
P30CA036727 ( US NIH Grant/Contract Award Number )
Study First Received: September 5, 2011
Last Updated: May 1, 2017

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on June 27, 2017