Ibrutinib and Rituxan for Chronic GVHD

Graft Vs Host Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04235036
• Other study ID #: NSH 1219
• Status: Terminated
• Phase: Phase 2
• Start date: December 16, 2019
• Est. completion date: December 23, 2022

Study information

• Verified date: November 2023
• Source: Northside Hospital, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 19
• Est. completion date: December 23, 2022
• Est. primary completion date: December 23, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Graft Vs Host Disease

Intervention

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).
• Ibrutinib
Ibrutinib is given orally every day (28-day cycles) for a total of 12 cycles.

Locations

Country	Name	City	State
United States	Northside Hospital	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Northside Hospital, Inc.	Pharmacyclics LLC.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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