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Ibrutinib and Rituxan for Chronic GVHD

Primary Purpose

Graft Vs Host Disease

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Rituximab
Ibrutinib
Sponsored by
Northside Hospital, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Graft Vs Host Disease focused on measuring ibrutinib, rituximab, cGVHD, chronic GVHD

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Northside HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Rituximab + Ibrutinib

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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)
The total cumulative steroid exposure measured by total milligrams received by each patient.
To estimate cumulative steroid exposure (total mg methylprednisolone or equivalent)
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).
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).
How many patients have not relapsed measured by progression-free survival at 12 months following the 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.
To estimate overall survival
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.
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.

Full Information

First Posted
August 19, 2019
Last Updated
October 19, 2022
Sponsor
Northside Hospital, Inc.
Collaborators
Pharmacyclics LLC.
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1. Study Identification

Unique Protocol Identification Number
NCT04235036
Brief Title
Ibrutinib and Rituxan for Chronic GVHD
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 16, 2019 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Northside Hospital, Inc.
Collaborators
Pharmacyclics LLC.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft Vs Host Disease
Keywords
ibrutinib, rituximab, cGVHD, chronic GVHD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Rituximab + Ibrutinib
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Ibrutinib
Intervention Description
Ibrutinib is given orally every day (28-day cycles) for a total of 12 cycles.
Primary Outcome Measure Information:
Title
The number of patients who remain off immunosuppressive therapy at 8 weeks after the initiation of treatment.
Description
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.
Time Frame
12 months following initiation of treatment
Secondary Outcome Measure Information:
Title
The number of patients who respond to treatment assessed by NIH Response Criteria Working Group Report.
Description
To estimate chronic GVHD response (CR + PR, both individual organ response and overall response, according to 2014 NIH Response Criteria Working Group Report)
Time Frame
12 months following initiation of treatment
Title
The total cumulative steroid exposure measured by total milligrams received by each patient.
Description
To estimate cumulative steroid exposure (total mg methylprednisolone or equivalent)
Time Frame
12 months following initiation of treatment
Title
How long it takes for patients to discontinue treatment defined as the date all systemic immunosuppressive therapy is discontinued after resolution of GVHD.
Description
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).
Time Frame
12 months following initiation of treatment
Title
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.
Description
To estimate failure-free survival (defined as being alive without the requirement for second-line cGVHD therapy).
Time Frame
12 months following initiation of treatment
Title
How many patients have not relapsed measured by progression-free survival at 12 months following the initiation of treatment.
Description
To estimate non-relapse mortality
Time Frame
12 months following initiation of treatment
Title
How many patients have not died measured by overall survival at 12 months following the initiation of treatment.
Description
To estimate overall survival
Time Frame
12 months following initiation of treatment
Title
Number of patients with treatment-related adverse events grade 3 or greater as assessed by CTCAE v.4.0.
Description
To estimate the incidence of grade 3 or greater adverse events, possibly or probably related to either ibrutinib and/or rituximab.
Time Frame
12 months following initiation of treatment
Title
Number of patients with treatment-related adverse events total as assessed by CTCAE v.4.0.
Description
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.
Time Frame
12 months following initiation of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Scott R Solomon, MD
Phone
404-255-1930
Email
ssolomon@bmtga.com
First Name & Middle Initial & Last Name or Official Title & Degree
Stacey Brown
Phone
404-780-7965
Email
stacey.brown@northside.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott R Solomon, MD
Organizational Affiliation
Northside Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Northside Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stacey Brown, BA
Phone
404-780-7965
Email
stacey.brown@northside.com
First Name & Middle Initial & Last Name & Degree
Caitlin Guzowski, MBA, MHA
Phone
404-851-8523
Email
caitlin.guzowski@northside.com
First Name & Middle Initial & Last Name & Degree
H. Kent Holland, MD
First Name & Middle Initial & Last Name & Degree
Asad Bashey, MD
First Name & Middle Initial & Last Name & Degree
Lawrence E Morris, MD
First Name & Middle Initial & Last Name & Degree
Scott Solomon, MD
First Name & Middle Initial & Last Name & Degree
Melhem Solh, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Ibrutinib and Rituxan for Chronic GVHD

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