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

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ClinicalTrials.gov Identifier: NCT02613598
Recruitment Status : Recruiting
First Posted : November 24, 2015
Last Update Posted : November 14, 2019
Sponsor:
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Hodgkin's Lymphoma Lymphoma, Non-Hodgkin Drug: Bortezomib Drug: Ruxolitinib Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : January 2016
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : October 2020


Arm Intervention/treatment
Experimental: Bortezomib and Ruxolitinib
Bortezomib 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.
Drug: Bortezomib
Other Name: Velcade

Drug: Ruxolitinib
Other Name: Jakafi




Primary Outcome Measures :
  1. The Maximum Tolerated Dose (MTD) of Ruxolitinib in Combination with Standard Dose Bortezomib [ Time Frame: Up to 5 Years ]


Information from the National Library of Medicine

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02613598


Contacts
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Contact: Tycel Phillips, M.D. 734-232-2883 tycelp@umich.edu

Locations
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United States, Michigan
University of Michgan Comprehensive Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48187
Contact: Tycel Phillips, M.D.    734-232-2883    tycelp@umich.edu   
Principal Investigator: Tycel Phillips, M.D.         
Sponsors and Collaborators
University of Michigan Rogel Cancer Center
Investigators
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Principal Investigator: Tycel Phillips, M.D. University of Michigan Rogel Cancer Center

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Responsible Party: University of Michigan Rogel Cancer Center
ClinicalTrials.gov Identifier: NCT02613598     History of Changes
Other Study ID Numbers: UMCC 2014.066
HUM00104716 ( Other Identifier: University of Michgan Medical School )
First Posted: November 24, 2015    Key Record Dates
Last Update Posted: November 14, 2019
Last Verified: November 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bortezomib
Antineoplastic Agents