Bortezomib in Combination With Ibrutinib in Ibrutinib Relapsed Mantle Cell Lymphoma

Phase II Study Evaluating the Effect of Adding Bortezomib to Ibrutinib in Ibrutinib Relapsed Mantle Cell Lymphoma

This is a phase II study to evaluate the efficacy of ibrutinib in combination with bortezomib in in MCL (mantle cell lymphoma) patients who relapsed on single agent ibrutinib.

Study Overview

• Status: Withdrawn
• Conditions: Mantle Cell Lymphoma
• Intervention / Treatment: Drug: Bortezomib; Drug: Ibrutinib

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48187
      • University of Michigan Rogel Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women ≥ 18 years of age
• Diagnosis of mantle cell lymphoma established by histologic assessment by a hemato-pathologist with additional assessment of the histologic diagnosis by immunohistochemistry or flow cytometry.
• Patients with history of MCL that has relapsed (documented disease progression after previously responding) to therapy (CR/PR) on single agent ibrutinib (treated for at least 6 months) as the last treatment prior to enrollment.
• Adequate liver, renal and bone marrow function
• Adequate coagulation (unless abnormalities are unrelated to coagulopathy or bleeding disorder)
• Female subjects of childbearing potential must have a negative urine/serum pregnancy test upon study entry. Women as well are not advised to breastfeed during treatment with bortezomib and for 2 months after treatment.
• Male and female subjects of reproductive potential must agree to use both a highly effective method of birth control and barrier method during the period of therapy and for 30 days after the last dose of study drug for females and 90 days for males.
• Eastern Cooperative Oncology Group (ECOG) performance status of <2 (Eastern Cooperative Oncology Group scoring system used to quantify general well-being and activities of daily life; scores range from 0 to 5 where 0 represents perfect health and 5 represents death.)

Exclusion Criteria:

• Concurrent diagnosis of another malignancy unless treated with curative intent more than 2 years from study start (basal/squamous cell carcinoma of the skin is not an exclusion).
• Previous treatment with bortezomib.
• Patients who are eligible for autologous stem cell transplant are excluded unless they refuse this procedure.
• History of allogeneic stem cell transplant.
• Other exclusions (certain concurrent conditions) per protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bortezomib + Ibrutinib; Ibrutinib will be administered orally at a dose of 560 mg daily for each 21 day cycle. Bortezomib will be administered subcutaneously at a dose of 1.3 mg/m^2 on days 1, 4, 8, and 11 of each 21-day cycle.	Drug: Bortezomib; Bortezomib will be administered subcutaneously at a dose of 1.3 mg/m^2 on days 1, 4, 8, and 11 of each 21-day cycle.; Drug: Ibrutinib; Ibrutinib will be administered orally at a dose of 560 mg daily for each 21 day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of participants that respond to treatment at 6 months	The primary endpoint is overall response rate (ORR). Participants will be evaluated for response based on the Lugano criteria.	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival time	Patients will be followed for survival until death or up to 10 years.	Up to 10 Years
Progression free survival time	Progression will be determined using the Lugano criteria. Patients will be followed for survival until death or up to 10 years.	Up to 10 Years
Best overall response	Participants will be evaluated for response based on the Lugano criteria. From the start of the study treatment until the disease progression/recurrence or up to 10 years.	Up to 10 Years
Rate of complete response	Participants will be evaluated for response based on the Lugano criteria. The percentage of participants who achieve CR after treatment.	Up to 10 Years
Time to progression	Progression will be determined using the Lugano criteria.	Up to 10 Years

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Investigators: Principal Investigator: Tycel Phillips, MD, University of Michigan Rogel Cancer Center

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2020
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): July 1, 2030

Study Registration Dates

• First Submitted: July 31, 2018
• First Submitted That Met QC Criteria: August 3, 2018
• First Posted (Actual): August 6, 2018

Study Record Updates

• Last Update Posted (Actual): June 22, 2020
• Last Update Submitted That Met QC Criteria: June 18, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Relapsed
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Mantle-Cell; Antineoplastic Agents; Bortezomib
• Other Study ID Numbers: UMCC 2018.046; HUM00139543 (Other Identifier: University of Michigan)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No