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

NCT02613598 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: UMCC 2014.066HUM00104716
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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).

Conditions

Hodgkin's Lymphoma; Lymphoma, Non-Hodgkin

Outcome Measures

Primary Outcomes (1)

• The Maximum Tolerated Dose (MTD) of Ruxolitinib in Combination with Standard Dose Bortezomib

  Up to 5 Years

Study Arms (1)

Bortezomib and Ruxolitinib

EXPERIMENTAL

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; Drug: Ruxolitinib

Interventions

Bortezomib DRUG

Also known as: Velcade

Bortezomib and Ruxolitinib

Ruxolitinib DRUG

Also known as: Jakafi

Bortezomib and Ruxolitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michgan Comprehensive Cancer Center

Ann Arbor, Michigan, 48187, United States

Location

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Non-Hodgkin

Interventions

Bortezomib; ruxolitinib

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Tycel Phillips, M.D.

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2015
• First Posted: November 24, 2015
• Study Start: May 12, 2016
• Primary Completion: June 7, 2021
• Study Completion: June 7, 2021
• Last Updated: December 20, 2021

Record last verified: 2021-12

Locations

US (1)