Clinical Trials /

Dose Escalation Study to Determine the Maximum Tolerated Dose of the Combination of Ruxolitinib and Bortezomib in Patients With Relapsed or Refractory Lymphoma

NCT02613598

Description:

The primary objective of this research study is to determine the maximum tolerated dose (MTD) of Ruxolitinib (Jakafi) in combination with standard dose Bortezomib (Velcade) in patients with relapsed or refractory Hodgkin (HL) and Non-Hodgkin Lymphoma (NHL).

Related Conditions:
  • Hodgkin Lymphoma
  • Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Dose Escalation Study to Determine the Maximum Tolerated Dose of the Combination of Ruxolitinib and Bortezomib in Patients With Relapsed or Refractory Lymphoma
  • Official Title: Phase I Dose Escalation Study to Determine the Maximum Tolerated Dose of the Combination of Ruxolitinib and Bortezomib in Patients With Relapsed or Refractory Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2014.066
  • SECONDARY ID: HUM00104716
  • NCT ID: NCT02613598

Conditions

  • Hodgkin's Lymphoma
  • Lymphoma, Non-Hodgkin

Interventions

DrugSynonymsArms
BortezomibVelcadeBortezomib and Ruxolitinib
RuxolitinibJakafiBortezomib and Ruxolitinib

Purpose

The primary objective of this research study is to determine the maximum tolerated dose (MTD) of Ruxolitinib (Jakafi) in combination with standard dose Bortezomib (Velcade) in patients with relapsed or refractory Hodgkin (HL) and Non-Hodgkin Lymphoma (NHL).

Detailed Description

      Treatment of relapsed and refractory Hodgkin and Non-Hodgkin's Lymphoma remains difficult. To
      improve upon current efficacy rates new treatment modalities are needed. Currently modalities
      based upon targeting specific pathway and molecular receptors have made the greatest impact
      in the outcomes of refractory patients.

      The JAK-Stat pathway and NF-κB are two such targets that have been shown to fuel the
      malignant transformation and growth of both myeloma and lymphoma. Blockade of key points in
      these molecular pathways has the potential of halting the pro-survival machinery. Combined
      inhibition of JAK/Stat and NF-κB may lead to synergistic effects as well as possibly
      mitigating some of the mechanisms of resistance to either agent. In this proposal, the
      investigators aim to utilize the JAK/Stat inhibitor ruxolitinib (Jakafi) and proteasome
      inhibitor bortezomib (Velcade) to target two major pathways of malignant transformation in
      hematologic malignancies.

      The primary objective of this research study is to determine the maximum tolerated dose (MTD)
      of Ruxolitinib (Jakafi) in combination with standard dose Bortezomib (Velcade) in patients
      with relapsed or refractory Hodgkin (HL) and Non-Hodgkin Lymphoma (NHL).

      The University of Michigan will enroll 24 subjects. Eligible subjects will have
      histologically or cytologically confirmed Hodgkin and Non-hodgkin's Lymphoma excluding
      Burkitt, CLL and lymphoblastic lymphoma that is considered to have relapsed or to be
      refractory to primary chemotherapy. Any prior exposure to Jakafi is excluded.
    

Trial Arms

NameTypeDescriptionInterventions
Bortezomib and RuxolitinibExperimentalBortezomib on days 1, 4, 8, and 11 of a 21 day cycle in combination with Ruxolitinib (5, 10, 15, 20, or 25 mg) twice daily.
  • Bortezomib
  • Ruxolitinib

Eligibility Criteria

        Inclusion Criteria:

          -  Women and men with histologically or cytologically confirmed Hodgkin and all NHL
             subtypes excluding Burkitt, CLL and lymphoblastic lymphoma that is considered to have
             relapsed or to be refractory to primary chemotherapy.

          -  No 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 have elapsed since prior large-field radiation therapy and all treatment
             related toxicity has resolved. 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 be at least 6 months from date of stem cell infusion,
             have no evidence of GVHD, be off all immunosuppressant medications, and have recovered
             to ≤ grade 1 toxicities related to this procedure.

          -  Age >18 years

          -  ECOG (Eastern Cooperative Oncology Group) Performance status ≤2

          -  Life expectancy without treatment > 12 weeks

          -  Patients must have adequate hematologic, hepatic, and renal function as defined as:
             Absolute neutrophil count ≥1,000/μl, Platelets ≥75,000/μl, (50,000/ μl if due to BM
             involvement), Direct bilirubin< 1.5 mg/dl, unless due to Gilbert's or secondary to
             hemolysis, AST (Aspartate Aminotransferase) and/or ALT (Alanine Transaminase) <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 and 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, patients must have
             stopped other experimental agents at least 21 days prior to 1st study dose.

          -  Any prior to exposure to Jakafi

          -  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 Jakafi or Velcade.

          -  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 because Jakafi is
             inhibitor of the Jak-1 and Jak-2 kinases with the potential for teratogenic or
             abortifacient effects. Because there is an unknown, but potential risk for adverse
             events in nursing infants secondary to treatment of the mother with Jakafi,
             breastfeeding should be discontinued if the mother is treated with Jakafi. These
             potential risks may also apply to other agents used in this study.

          -  HIV-positive patients on combination antiretroviral therapy are ineligible because of
             the potential for pharmacokinetic interactions with Jakafi. In addition, these
             patients are at increased risk of lethal infections when treated with marrow
             suppressive therapy. Appropriate studies will be undertaken in patients receiving
             combination antiretroviral therapy when indicated.

          -  Patients with grade 2 or higher peripheral neuropathy are excluded.

          -  Patients with CLL (Chronic Lymphocytic Leukemia), Burkitt or lymphoblastic lymphoma
             are excluded.

          -  Patients who would be required to concurrently take ruxolitinib in conjunction with a
             strong 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The Maximum Tolerated Dose (MTD) of Ruxolitinib in Combination with Standard Dose Bortezomib
Time Frame:Up to 5 Years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Michigan Rogel Cancer Center

Last Updated

November 13, 2019