Ruxolitinib Phosphate (Oral JAK Inhibitor INCB18424) in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell or Peripheral T-Cell Non-Hodgkin Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by University of Nebraska
Sponsor:
Collaborator:
Incyte Corporation
Information provided by (Responsible Party):
Julie M Vose, MD, University of Nebraska
ClinicalTrials.gov Identifier:
NCT01431209
First received: September 5, 2011
Last updated: March 8, 2014
Last verified: March 2014
  Purpose

This phase II trial studies how well giving ruxolitinib phosphate (oral JAK inhibitor INCB18424) works in treating patients with relapsed or refractory diffuse large B-cell or peripheral T-cell non-hodgkin lymphoma and are ineligible to stem cell transplant or have recurrent disease after 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
Peripheral T-cell Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Drug: oral JAK inhibitor INCB18424
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
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 University of Nebraska:

Primary Outcome Measures:
  • Number of patients achieving overall response rate [ Time Frame: after 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of treatment-emerged adverse events (new or worsening from baseline) as summarized by severity and type according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 30 days after study treatment has ended ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
    The Kaplan-Meier method will be used to estimate the median duration of response and its 95% confidence interval (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 ] [ Designated as safety issue: No ]
    The Kaplan-Meier method will be used to estimate PFS and its 95% CI.

  • 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 ] [ Designated as safety issue: No ]
    The Kaplan-Meier method will be used to estimate the median OS time and its 95% CI.


Estimated Enrollment: 90
Study Start Date: August 2011
Estimated Study Completion Date: August 2025
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (oral ruxolitinib phosphate)
Patients receive ruxolitinib phosphate (oral JAK inhibitor INCB18424) PO BID. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: oral JAK inhibitor INCB18424
Patients receive ruxolitinib phosphate (oral JAK inhibitor INCB18424) PO BID. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other Name: oral Janus-associated kinase inhibitor INCB18424
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies

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.

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-κB, BCR, 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 (oral JAK inhibitor INCB18424) orally (PO) twice daily (BID). 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:   19 Years and older
Genders Eligible for Study:   Both
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
  • 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
  • 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 >= 60mL/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 through follow-up
  • Males must agree to take appropriate precautions to avoid fathering a child from screening through follow-up
  • 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

Contacts
Contact: Susan Blumel, RN 402-559-9183 sblumel@unmc.edu
Contact: Lisa Houdesheldt 402-559-4596 lhoudesheldt@unmc.edu

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Melissa Harvey    507-266-3784    harvery.melissa@mayo.edu   
Principal Investigator: Thomas Witzig, MD         
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198-7830
Contact: Susan Blumel, RN    402-559-9183    sblumel@unmc.edu   
Principal Investigator: Julie Vose, MD         
United States, Texas
University of Texas, MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Javier R R Knickerbocker, APN    713-792-2860    jknicker@mdanderson.org   
Principal Investigator: Yasuhiro Oki, MD         
Sponsors and Collaborators
University of Nebraska
Incyte Corporation
Investigators
Principal Investigator: Julie M Vose, MD University of Nebraska
  More Information

No publications provided

Responsible Party: Julie M Vose, MD, Neumann M. and Mildred E. Harris Professor, Chief, Division of Hematology/Oncology, University of Nebraska
ClinicalTrials.gov Identifier: NCT01431209     History of Changes
Other Study ID Numbers: 283-11
Study First Received: September 5, 2011
Last Updated: March 8, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 29, 2014