Ibrutinib and Rituxan for Chronic GVHD

Phase 2

Terminated

Conditions: Graft Vs Host Disease

Interventions: Drug: Rituximab
Drug: Ibrutinib

Registration Number: NCT04235036

Lead Sponsor: Northside Hospital, Inc.

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 15

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Rituximab + Ibrutinib	Rituximab	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.
Rituximab + Ibrutinib	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.

Primary Outcome Measures

Name	Time	Method
The Number of Patients Who Remain Off Immunosuppressive Therapy at 12 Months After the Initiation of Treatment.	12 months following 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.

Secondary Outcome Measures

Name	Time	Method
The Number of Patients Who Respond to Treatment Assessed by NIH Response Criteria Working Group Report.	12 months following initiation of treatment	To estimate chronic GVHD response (CR + PR, both individual organ response and overall response, according to 2014 NIH Response Criteria Working Group Report \[CR - resolution of all manifestations in each organ or site; PR - improvement in at least 1 organ or site without progression in any other organ or site\])
How Long it Takes for Patients to Discontinue Treatment Defined as the Date All Systemic Immunosuppressive Therapy is Discontinued After Resolution of GVHD.	Up to 32 months	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).
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.	12 months following initiation of treatment	To estimate failure-free survival (defined as being alive without the requirement for second-line cGVHD therapy).
How Many Patients Have Not Relapsed Measured by Progression-free Survival at 12 Months Following the Initiation of Treatment.	12 months following initiation of treatment	To estimate non-relapse mortality
How Many Patients Have Not Died Measured by Overall Survival at 12 Months Following the Initiation of Treatment.	12 months following initiation of treatment	To estimate overall survival
Number of Patients With Treatment-related Adverse Events Grade 3 or Greater as Assessed by CTCAE v.4.0.	12 months following initiation of treatment	To estimate the incidence of grade 3 or greater adverse events, possibly or probably related to either ibrutinib and/or rituximab.
Number of Patients With Treatment-related Adverse Events Total as Assessed by CTCAE v.4.0.	12 months following initiation of treatment	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.