Ibrutinib and Rituxan for Chronic GVHD

Phase II Trial Evaluating the Safety and Efficacy of Combined CD20- and BTK-Targeted B Cell Depleting Therapy With Rituximab and Ibrutinib in the Primary Treatment of Chronic Graft-Versus-Host Disease

This is a phase II trial evaluating the safety and efficacy of the combination of Ibrutinib and Rituximab as primary treatment of chronic GVHD. We plan to enroll 35 patients on this study. Patients will be formally monitored monthly for 12 months to evaluate for outcome and safety endpoints. All other assessments will be done at the physician's discretion or institutional standards. All patients, responders and treatment failures, will be followed for a period of one year from the time of initiation of therapy. The primary endpoint will be the proportion of patients that are alive and off all systemic IST at 12 months following initiation of treatment.

Study Overview

• Status: Terminated
• Conditions: Graft Vs Host Disease
• Intervention / Treatment: Drug: Rituximab; Drug: Ibrutinib

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Scott R Solomon, MD; Phone Number: 404-255-1930; Email: ssolomon@bmtga.com

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• First episode of systemic immunosuppression-requiring cGVHD, defined as classic or overlap cGVHD by the NIH consensus criteria.
• Previously untreated cGVHD, defined by having received <10 days of corticosteroids or alternative systemic immunosuppressive agent started specifically for a new diagnosis of cGVHD.
• KPS 70% or greater

Exclusion Criteria:

• Late persistent or recurrent acute GVHD
• Active uncontrolled infection
• History of HIV infection; active HBV or HCV infection
• Inability to tolerate oral medications
• Progressive or recurrent malignancy following allogeneic transplant
• Exposure to BTK inhibitor following transplant
• Received prior treatment with ECP for cGVHD

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: Rituximab + Ibrutinib; Eligible patients will be those with a first episode of symptomatic cGVHD, requiring systemic immunosuppression for control of symptoms. Following study entry, patients will be started on rituximab plus ibrutinib.	Drug: Rituximab; Rituximab is given IV weekly x 4 weeks (to be started on study day 7 ± 3 days), then IV q3months x 4 doses (months 4, 7, 10, 13).; Drug: Ibrutinib; Ibrutinib is given orally every day (28-day cycles) for a total of 12 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of patients who remain off immunosuppressive therapy at 8 weeks after the initiation of treatment.	The primary objective is to evaluate the efficacy of the combination of rituximab and ibrutinib versus the historical experience with rituximab alone in the upfront treatment of cGVHD. Patients will be followed for 12 months following the initiation of treatment to see if they remain off immunosuppressive therapy for at least 8 weeks.	12 months following initiation of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of patients who respond to treatment assessed by NIH Response Criteria Working Group Report.	To estimate chronic GVHD response (CR + PR, both individual organ response and overall response, according to 2014 NIH Response Criteria Working Group Report)	12 months following initiation of treatment
The total cumulative steroid exposure measured by total milligrams received by each patient.	To estimate cumulative steroid exposure (total mg methylprednisolone or equivalent)	12 months following initiation of treatment
How long it takes for patients to discontinue treatment defined as the date all systemic immunosuppressive therapy is discontinued after resolution of GVHD.	To estimate time to discontinuation of systemic immunosuppression (defined as the date that all systemic IST has been discontinued after resolution of all reversible manifestations of cGVHD).	12 months following initiation of treatment
How many patients are still alive without the requirement for second-line cGVHD therapy measured by overall survival at 12 months following the initiation of treatment.	To estimate failure-free survival (defined as being alive without the requirement for second-line cGVHD therapy).	12 months following initiation of treatment
How many patients have not relapsed measured by progression-free survival at 12 months following the initiation of treatment.	To estimate non-relapse mortality	12 months following initiation of treatment
How many patients have not died measured by overall survival at 12 months following the initiation of treatment.	To estimate overall survival	12 months following initiation of treatment
Number of patients with treatment-related adverse events grade 3 or greater as assessed by CTCAE v.4.0.	To estimate the incidence of grade 3 or greater adverse events, possibly or probably related to either ibrutinib and/or rituximab.	12 months following initiation of treatment
Number of patients with treatment-related adverse events total as assessed by CTCAE v.4.0.	To evaluate the safety and tolerability of combination of rituximab and ibrutinib versus the historical experience with rituximab alone in the upfront treatment of cGVHD.	12 months following initiation of treatment

Collaborators and Investigators

• Sponsor: Northside Hospital, Inc.
• Collaborators: Pharmacyclics LLC.
• Investigators: Principal Investigator: Scott R Solomon, MD, Northside Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2019
• Primary Completion (Actual): December 23, 2022
• Study Completion (Actual): December 23, 2022

Study Registration Dates

• First Submitted: August 19, 2019
• First Submitted That Met QC Criteria: January 17, 2020
• First Posted (Actual): January 21, 2020

Study Record Updates

• Last Update Posted (Actual): November 9, 2023
• Last Update Submitted That Met QC Criteria: November 7, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: rituximab; ibrutinib; cGVHD; chronic GVHD
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: NSH 1219

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