Ruxolitinib Phosphate and Bortezomib in Treating Patients with Relapsed or Refractory Lymphoma

Status: Active

Description

This phase I trial studies the side effects and best dose of ruxolitinib phosphate and bortezomib in treating patients with relapsed or refractory lymphoma. Ruxolitinib phosphate and bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Eligibility Criteria

Inclusion Criteria

  • Histologically or cytologically confirmed Hodgkin and all NHL subtypes excluding Burkitt, chronic lymphocytic leukemia (CLL) and lymphoblastic lymphoma that is considered to have relapsed or to be refractory to primary chemotherapy
  • Prior chemotherapy provided patients have been off previous anti-cancer therapy for at least 21 days and recovered from all treatment related toxicity
  • Prior radiation is allowed prior to study start (1st dose of study medication) if at least 21 days must have elapsed since prior large-field radiation therapy and recovered from all treatment related toxicity; at least 3 months must have passed since radio-immunotherapy
  • Prior auto graft is allowed prior to study start (1st dose of study medication), but patients must be at least 3 months from date of stem cell infusion and have recovered to =< grade 1 toxicities related to this procedure
  • Prior allogeneic transplants is allowed prior to study start (1st dose of study medication), but patients must also be at least 6 months from date of stem cell infusion, have no evidence of graft versus host disease (GVHD), be off all immunosuppressant medications, and have recovered to =< grade 1 toxicities related to this procedure
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Life expectancy without treatment > 12 weeks
  • Absolute neutrophil count >= 1,000/ul
  • Platelets >= 75,000/ul, (50,000/ul if due to bone marrow [BM] involvement)
  • Direct bilirubin < 1.5 mg/dl, unless due to Gilbert’s or secondary to hemolysis
  • Aspartate aminotransferases (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and/or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 X institutional upper limit of normal unless due to lymphomatous involvement of the liver
  • Creatinine < 1.5 mg/dl and/or creatinine clearance > 60 mL/min using the Cockcroft-Gault formula
  • No symptoms attributable to grade 2 or higher peripheral neuropathy
  • Should a woman become pregnant or suspect that she is pregnant while she or her partner is participating in this study, she should inform the treating physician immediately
  • Subjects must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

  • Patients who are currently receiving any other experimental agent, must have stopped other experimental agents at least 21 days prior to 1st study dose
  • Any prior to exposure to ruxolitinib
  • Patients with untreated brain metastases are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib or bortezomib
  • Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant or breastfeeding women are excluded from this study
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • Patients with grade 2 or higher peripheral neuropathy are excluded
  • Patients with CLL, Burkitt or lymphoblastic lymphoma are excluded
  • Patients who would be required to concurrently take ruxolitinib in conjunction with a strong cytochrome p450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors and have a platelet count less than 100,000 are ineligible for the study
  • Patient who are required to take a strong CYP3A4 inducer are excluded from the study

Locations & Contacts

Michigan

Ann Arbor
University of Michigan Comprehensive Cancer Center
Status: Active
Contact: Tycel J. Phillips
Phone: 734-232-2883
Email: Tycelp@med.umich.edu

Trial Objectives and Outline

PIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of ruxolitinib phosphate (ruxolitinib) (Jakafi) in combination with standard dose bortezomib (Velcade) in patients with relapsed or refractory Hodgkin (HL) and non-Hodgkin lymphoma (NHL).

SECONDARY OBJECTIVES:

I. Evaluate the expression of signal transducer and activator of transcription (Stat)3/5 and phosphorylated Stat3/5 in tumor cells pre- and post-treatment.

II. Evaluate the effect that Janus kinase (JAK)/Stat inhibition has on the expression and localization of nuclear factor kappa B (NF-kappa B).

III. To measure the effect of JAK/Stat inhibition on serum and tumor levels of interleukin (IL)-6, IL-10.

IV. Obtain a preliminary estimate of disease response to therapy.

OUTLINE: This is a dose-escalation study.

Patients receive ruxolitinib phosphate orally (PO) twice daily (BID) on days 1-21 and bortezomib subcutaneously (SC) on days 1, 4, 8 and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then up to 6 months.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
University of Michigan Comprehensive Cancer Center

Principal Investigator
Tycel Phillips

Trial IDs

Primary ID UMCC 2014.066
Secondary IDs NCI-2016-00457
Clinicaltrials.gov ID NCT02613598